Endversion1 skriptum characterization of miscellaneous multi parametrical silicon based biosensor...

Table of contents

Characterization of miscellaneous multi parametrical silicon based biosensor chips - 1 -

Table of contents Table of contents .................................................................................................................. 1

1 Introduction .................................................................................................................. 4

2 Materials and methods.............................................................................................. 7

2.1 Microscopes ..................................................................................................................... 7 2.1.1 Purpose of use ............................................................................................................................................ 8 2.1.2 Used equipment and items ................................................................................................................... 8 2.1.3 Available settings ...................................................................................................................................... 8

2.2 Used PC software ........................................................................................................... 9

2.3 Phosphate-Buffered Saline (PBS) .......................................................................... 11

2.4 Ag/AgCl reference electrode ................................................................................... 12 2.4.1 Purpose of use ......................................................................................................................................... 12 2.4.2 Used equipment and items for production ................................................................................ 13 2.4.3 Producing assembly ............................................................................................................................. 14 2.4.4 Production procedure ......................................................................................................................... 15

2.5 Incubator ........................................................................................................................ 17 2.5.1 Purpose of use ......................................................................................................................................... 17 2.5.2 Available settings ................................................................................................................................... 18

2.6 Regulated DC power supply unit ........................................................................... 19 2.6.1 Purpose of use ......................................................................................................................................... 19 2.6.2 Available settings ................................................................................................................................... 20

2.7 Voltalab® 80/10 .......................................................................................................... 21 2.7.1 Purpose of use ......................................................................................................................................... 21 2.7.2 Available settings ................................................................................................................................... 21

2.8 Sensor chips .................................................................................................................. 26 2.8.1 cMOS ............................................................................................................................................................ 27 2.8.2 nMOS ........................................................................................................................................................... 30

2.9 Pin box ............................................................................................................................. 34 2.9.1 Purpose of use ......................................................................................................................................... 34 2.9.2 Available connectors ............................................................................................................................ 35

2.10 Non-Semiconductor sensors ................................................................................... 38 2.10.1 Clark sensor (Amperometry) ........................................................................................................... 38

2.10.1.1 Idea ................................................................................................................................................... 38 2.10.1.2 Equipment and items ............................................................................................................... 41 2.10.1.3 Measurement assembly .......................................................................................................... 43 2.10.1.4 Measurement settings and parameters ........................................................................... 44

Table of contents

- 2 - Characterization of miscellaneous multi parametrical silicon based biosensor chips

2.10.1.5 Procedure ...................................................................................................................................... 45 2.10.2 IDES Sensor (Impedimetric) ............................................................................................................. 46

2.10.2.1 Idea ................................................................................................................................................... 46 2.10.2.2 Equipment and items ............................................................................................................... 48 2.10.2.3 Measurement assembly .......................................................................................................... 49 2.10.2.4 Measurement settings and parameters ........................................................................... 50 2.10.2.5 Procedure ...................................................................................................................................... 51

2.11 Semiconductor sensors ............................................................................................. 52 2.11.1 Temperature Diode (Potentiometry) ........................................................................................... 52

2.11.1.1 Idea ................................................................................................................................................... 52 2.11.1.2 Equipment and items ............................................................................................................... 54 2.11.1.3 Measurement assembly .......................................................................................................... 55 2.11.1.4 Measurement settings and parameters ........................................................................... 56 2.11.1.5 Procedure ...................................................................................................................................... 56

2.11.2 Reference MISFET (nMOS) ................................................................................................................ 57 2.11.2.1 Idea ................................................................................................................................................... 57 2.11.2.2 Equipment and items ............................................................................................................... 59 2.11.2.3 Measurement assembly .......................................................................................................... 61 2.11.2.4 Measurement settings and parameters ........................................................................... 61 2.11.2.5 Procedure ...................................................................................................................................... 61

2.11.3 ISFET Sensors for pH-Measurement ............................................................................................. 62 2.11.3.1 Idea ................................................................................................................................................... 62 2.11.3.2 Equipment and items ............................................................................................................... 63 2.11.3.3 Measurement assembly .......................................................................................................... 65 2.11.3.4 Measurement settings and parameters ........................................................................... 66 2.11.3.5 Procedure ...................................................................................................................................... 66

2.11.4 O2-FET Sensors for DO-Measurement .......................................................................................... 67 2.11.4.1 Idea ................................................................................................................................................... 67 2.11.4.2 Equipment and items ............................................................................................................... 69 2.11.4.3 Measurement assembly .......................................................................................................... 72 2.11.4.4 Measurement settings and parameters ........................................................................... 72 2.11.4.5 Procedure ...................................................................................................................................... 73

2.11.5 CV-FET (an extended O2-FET Sensor) .......................................................................................... 74 2.11.5.1 Idea ................................................................................................................................................... 74 2.11.5.2 Measurement settings and parameters ........................................................................... 75 2.11.5.3 Procedure ...................................................................................................................................... 75

3 Results and Discussion ........................................................................................... 77

3.1 Non-Semiconductor sensors ................................................................................... 77 3.1.1 Clark sensor ............................................................................................................................................. 77

3.1.1.1 cMOS chips .................................................................................................................................... 78 3.1.1.2 nMOS chips ................................................................................................................................... 79

3.1.2 IDES Sensor .............................................................................................................................................. 80 3.1.2.1 cMOS chips .................................................................................................................................... 80 3.1.2.2 nMOS chips ................................................................................................................................... 80

3.2 Semiconductor sensors ............................................................................................. 82 3.2.1 Temperature Diode .............................................................................................................................. 82


Table of contents


3.2.2 Reference MOSFET (nMOS) .............................................................................................................. 85 3.2.3 ISFET Sensor ............................................................................................................................................ 86


3.2.4 O2-FET Sensor ......................................................................................................................................... 90 3.2.4.1 cMOS chips .................................................................................................................................... 90 3.2.4.2 nMOS chips ................................................................................................................................... 91

3.2.5 CV-FET Sensor (nMOS) ....................................................................................................................... 93

4 Problems and Solutions ......................................................................................... 99

4.1 Contacting errors ........................................................................................................ 99

4.2 Loosing of the passivation layer ......................................................................... 100

4.3 Noise.............................................................................................................................. 103

4.4 Signal drops while measuring ............................................................................. 104

4.5 Digital rounding errors .......................................................................................... 104

4.6 Unclean sensor surface .......................................................................................... 105

5 Conclusions and outlook ...................................................................................... 106

6 Acknowledgments .................................................................................................. 109

7 Indexes ....................................................................................................................... 110

7.1 Index of pictures ....................................................................................................... 110

7.2 Index of graphs .......................................................................................................... 111

7.3 Index of equations.................................................................................................... 112

7.4 Index of tables ........................................................................................................... 112

8 List of abbreviations and symbols .................................................................... 114

9 Bibliography ............................................................................................................ 119

10 Appendix ............................................................................................................... 123

Introduction


1 Introduction The biomedical analysis techniques require the development of smart sensors with the following properties: mass fabrication, low cost, low power and ease of use. In this goal, various sensors have been developed to cover the needs of the biomedical researches. In these researches, biological cell cultures are analyzed under different conditions. The biochemical activities of these cultures change some parameters of the environment which they live in. This environment can be enclosed and protected from any outer effects, so any changes by the living biological cells can be detected using various detecting methods. One of these methods is the electrochemistry, which is the detecting of electrical signals caused by chemical reaction. An electrochemical cell is a chemically and electrically isolated environment. Therefore the isolated environment, which the biological cells live in, can be handled as an electrochemical cell.

Electrochemical cell. Picture 1-1

Introduction


There are three basic electrochemical cell processes that are useful in transducers for sensor applications:

1. Potentiometry, the measurement of a cell potential at zero current.

2. Voltammetry and analogue amperometry, in which an oxidizing potential is applied between the cell electrodes and the cell current is measured.

3. Conductometry, where the conductance and resistance of the cell is

measured by an alternating current bridge method. Semiconductor sensors have the advantage that they have smaller dimensions then other materials and several sensor types can be easily integrated in one chip. Electronic miniature circuits and structures e.g. memory or amplifier can produced in the same wafer with the sensor at the same time. On the other hand, only mass produced semiconductor sensors are economically producible. Alternatively, researches are also done using thin film technology to produce sensors on glass or ceramic. This is cheaper and easier. Because the rapid development the semiconductor production and the high quality at small dimensions, the silicon sensors are not to disregard. Therefore the Lehrstuhl für medizinische Elekronik – the Chair for medical electronics- at Technische Universität München has developed silicon sensor chips to monitor the activity of living cell. The most important parameters to measure are oxygen concentration and pH value under monitoring temperature and adhesion.

Used sensors on silicon and thin film technologies. Table 1-1

For the pH measurement, the ion-sensitive field effect transistor (ISFET) was used. It provides all the requested advantages and its potentiometric principle is well adapted to the detection of ions for pH value. Thus, many researches to increase the pH sensitivity were done for the development of ISFETs.

Parameter [MICH06]

Silicon technology

Thin film technology

Temperature pn diode Pt1000 Dissolved

oxygen Clark Sensor

O2-FET Clark Sensor pH ISFET Metal oxide

Introduction


Because the ISFETs were only for measuring pH it was not able to detect dissolved oxygen in the electrolyte fluid without disturbing it with other substances to cause a chemical reaction resulting in change of pH value. It was not possible to limit this chemical reaction to be locally, so the same fluid can be used again. A solution for this problem was to use electrochemical half reactions, which can be controlled very locally and without the need to add other substances. The electrochemical half reactions can be produced by applying a potential at an electrode, which is small enough to keep the reaction locally. The produced ions are only in the surrounding area but in the same time they are enough to produce an electrical potential to be detected by the ISFET sensor. For this an O2-FET was developed and evaluated successfully. The work idea for O2-FET was also to be generalized to measure other dissolved materials than oxygen. This requires the improvement of the O2-FET measurement procedures from a pulse operating mode to a cyclovoltammetrical scan mode, so the measured values are significant to concentration of substances we want to detect. In addition to O2-FET, a Clark type sensor -which is also on the same chip-, can be used for measuring dissolved oxygen and confirm the results of the O2-FET. The main work points in this assay are:

1. Examine the sensor chips of visible production errors.

2. Investigating available measurement methods.

3. Theoretical explanation of the measuring methods.

4. Construction of measurement system for each sensor.

5. Procedure of measurements.

6. Discussion of the measured data.

7. Determination of malfunction and failure sources.

8. Development and improvement the measurement procedures.

Materials and methods


2 Materials and methods In this chapter the used materials for the characterization of the sensor chips are presented. Recommended working steps and available setting of the used equipment are also described. 2.1 Microscopes

The used microscopes with digital cameras. Picture 2-1



2.1.1 Purpose of use To examine the sensor chips optically for visual manufacturing errors before the beginning of the evaluating. Comparing the pictures of the sensors before and after measuring will give lot of information about its aging process and it is opportunity to specify common errors of the chips. 2.1.2 Used equipment and items DIGITAL CAMERAS:

Nikon E4300: Was used to take the pictures using the first microscope with the high magnification factor.

Nikon E5400: It was connected to the second microscope.

CARD READER:

To transfer the photos taken by the camera from the memory card, where the cameras save the photo files, to a PC using the USB port.

2.1.3 Available settings The pictures were taken with the digital cameras. The digital camera was connected to the microscope by an optical adapter with lens. Additional the optical zoom of the camera is also used. An accurate zoom factor therefore cannot be given. The first microscope has a bigger zoom factor and it can only magnify the individual sensors on the chip. The second microscope cannot magnify as good as the first one, but it used for taking pictures of the whole chip surface.



2.2 Used PC software ORIGIN PRO 8:

It is a professional data analysis and graphing software for engineers. It can handle huge amount of data more efficient than other programs. Its multi-sheet workbooks, publication-quality graphics, and standardized analysis tools provide a tightly integrated workspace to import data, create and annotate graphs, explore and analyze data, and publish work.

VOLAMASTER 4 V7.08:

It is software with an easy configurable measurement sequence editor for the Voltalab measuring unit. It gives the possibility to monitor the detected response signal in real time and record these values in data tables. The program VoltaMaster 4 has also the ability to show the captured data in graphs, apply filters, and change parameters to highlight information.

MS WORD 2007:

A good known word processing software. The version 2007 uses a new file format called docx. Word 2000-2003 users on Windows systems can install a free add-on called the "Microsoft Office Compatibility Pack" to be able to open, edit, and save the new Word 2007 files. Alternatively, Word 2007 can save to the old doc format of Word 97-2003 and edit it, but then is not possible to use the “Equation Editor” any more.

MS PAINT: A simple graphics painting program that has been included with almost all versions of MS Windows. The used Windows version is Vista, which has more undo levels and better crop functions. The main improvement is to add zoom slider, which increased the work speed with small objects. The program can edit and save in the most known non layer graphic file formats.



MS POWERPOINT 2007:

To make a presentation of this work with figures and animations.

ADOBE ILLUSTRATOR CS3:

Used to design some figures in vector graphics format.

MS EXCEL XP/2007: To plot the raw data of the acquired measurements in graphs and diagrams.

MATHTYPE 6.0:

A plug-in for MS Office package as an alternative to the Equation Editor which comes with MS Office.

ADOBE ACROBAT PROFESSIONAL 8:

To make a PDF version of this electronic document for the publication. Files in PDF format are platform independent and contain the fonts used in the document.

MS VISIO 2007:

Used to design some figures in vector graphics format, it contains also a graphic library to use in making data flow diagrams and work plans.



2.3 Phosphate-Buffered Saline (PBS) PBS solution is used widely in biochemistry and biological research. That’s because its osmolarity and ion concentration usually match those of the human body, and because it maintains a constant pH value. = ℎ

Molarity Equation. Equation 2-1

PBS buffer composition. Table 2-1

The PBS solution used has a pH value of about 7.15. BONDING DISSOLVED OXYGEN In addition, to bond from air dissolved oxygen molecules in the PBS it is enough to add 10g sodium sulfite Na2SO3 to 1l PBS. For an accurate measurement this solution must be used fresh. The resulted PBS has a pH value of about 8.10.

Used sodium sulfite concentration for bonding dissolved oxygen. Table 2-2

Components [MICH06]

Mole Weight (g/mol)

Concentration (g/l)

Molarity (mM)

KH2PO4 136 0.20 1.47 NaCl 58.5 8.00 138 Na2HPO4 * 2H2O 178 1.44 8.1 KCl 74.6 0.20 2.68

Substance [GEST08]

Mole Weight (g/mol)

Concentration (g/l)

Molarity (mM)

Na2SO3 126 10.00 79.4



MORE FREE IONS To make solutions with more dissolved free ions than 150mM of NaCl, we add 8.8g to one liter PBS to double the molarity to 300mM. To make several concentrations it is easier to dilute a higher concentrated solution with PBS. For concentrations below molarity of a usual PBS we add deionised water.

Concentration of the NaCl to double the amount of the free ions. Table 2-3

2.4 Ag/AgCl reference electrode Reference electrode is an electrode which has a stable and known potential. The stability of the electrode potential is reached by employing a redox system with constant concentrations. 2.4.1 Purpose of use Reference electrodes are used to keep the electrolyte at a constant potential, without causing electrical current to flow within the electrolyte. The reference electrode is difficult to build on the silicon chip by using integrated circuit technology. That is because a reference electrode uses an electro chemical reaction to move ions from an electrode into solution. A silver/silver chloride wire is used as reference electrode due these features:

- Stable standard potential of 0.2V [MACA78]. - Non-toxic components. - Simple construction. - Inexpensive to manufacture.

Substance [MICH06]

Mole Weight (g/mol)

Concentration (g/l)

Molarity (mM)

NaCl 58.5 16.80 288



The motion of chloride ions at Ag/AgCl wire causes current, which can be explained as [FARM98]:

e- + AgCl ↔ Ag + Cl-

Reference electrode current. Equation 2-2

The corresponding Nernst equation for this reaction is: = − ln [ ]

The voltage of reference electrode. Equation 2-3

To avoid current to flow through the electrode and then to the electrolyte, a 3M KCl solution is used. 2.4.2 Used equipment and items for production VOLTALAB:(PULSE-CHRONO POTENTIOMETRY)

The current that will flow though the electrolyte is set to constant value. The corresponding voltage is also recorded.

SILVER AG WIRE: Cut in handy 4cm peaces wire.

PLATINUM PT WIRE: One peace 4cm wire.

HYDROCHLORIC ACID HCL SOLUTION: With a molarity of 0.1M.



2.4.3 Producing assembly Electrolysis by electrochemical oxidation of the silver wire in 0.1mM hydrochloric acid HCl solution: - Ag as anode at the plus pole (Work-Prot) of the voltage source Voltalab. - Pt as cathode at the minus pole (Ref-Port) of Voltalab.

Wiring schema for the production of Ag/AgCl electrode. Picture 2-2 While producing an AgCl on the Ag wire the following chemical reactions happen: On the Ag-Anode side: 2Ag + 2 HCl à 2 AgCl + 2 H+ + 2 e- (AgCl is darker than Ag)

Half reaction the Ag side. Equation 2-4

On the Pt-Cathode side: 2 H+ + 2 e- à H2 (H2 bubbles rise on Pt)

Half reaction the Pt side. Equation 2-5



So the whole reaction can be summed to:

2 Ag + HCl à 2 AgCl + H2

The whole chemical reaction for producing Ag/AgCl electrode. Equation 2-6

2.4.4 Production procedure

1. A constant current of 4mA to flow through the electrodes is applied

2. Becoming the silver wire darker and rising hydrogen gas on the platinum wire is an indicator for building silver chloride.

The measured electrolysis voltage at 4mA for producing Ag/AgCl. Graph 2-1

3. After few minutes (4 minutes) the hydrogen bubbles will stop to develop on the platinum side, this means the silver chloride is already reached its maximal thickness on the silver wire.

-1,7

-1,6

-1,5

-1,4

-1,3

-1,2

-1,1

-1

-0,9

-0,8

-0,7

0 50 100 150 200 250Time [s]

Volta

ge [V

]



Electrolysis current for producing Ag/AgCl. Graph 2-2 This period can be also known from the electrolysis current curve below, where the current a 1mA doesn’t change anymore, if we applied a constant voltage instead of current.



2.5 Incubator

The used incubator. Picture 2-3 The used incubator is Kelvitron t6030 from Heraeus Instruments. It has a volume of 30l and offers enough space to set the sensors and its pin box, without having an unneeded free volume to heat. The more volume there is to heat the more time is needed to reach the target temperature. 2.5.1 Purpose of use To make and keep a constant tempered environment for temperature dependent measurements.



The incubator can be also used as faraday cage. 2.5.2 Available settings The incubator can heat up to 300°C. Therefore, it is not possible to have a temperature below environment temperature in the room. Although, it accepts settings below room temperature, but this practically cannot be realized. Cooling down takes several hours. So, when measuring at many temperatures, it is easier and faster to begin with the lowest temperature.

Damped oscillations of the incubator. Graph 2-3 Heating up the air in the incubator to a constant target temperature needs relatively long time compared e.g. to a fan oven. This is because the oscillation of the heating process of the incubator, which uses pulsed operating of the heating elements without circulating the air. The bigger the difference between target and start temperatures is, the bigger is the oscillation amplitude and time to get a constant target temperature.



2.6 Regulated DC power supply unit

The used Power supply [CONR08]. Picture 2-4 Laboratory power supply VLP-1303 PRO delivers constant potential difference between its input minus port and output plus port. The potential difference can be adjusted manually and displayed with its corresponding current flowing through the ports. The voltmeter is used to control the adjusted voltage. The display of the power supply has not enough digits to display the applied voltage exactly. The display can have here a rounding error up to 100%, because the missing second and third digit after the radix point, which can be 99, a voltage of 0.099V can be shown inaccurate on the units display as “00.0V”. 2.6.1 Purpose of use The voltage supplied by this unit is used to raise the potential of the gate above the source potential on the reference MOSFET of nMOS chips. This potential builds the electrons channel between source and drain. Through this channel can current flow. The width of this channel is controlled by the applied voltage at gate using this power supply. This voltage must be very constant; otherwise the small changes of this voltage can affect the transistor current very much, so the characterization cannot be done as desired.



2.6.2 Available settings The power supply has two outputs. The first output has a range of 0V to 3V at a maximal current of 3A. The second output has a range of 3V to 6V at maximal current of 2A. The unit -beside the supplying of a constant voltage- can also limit the current flow through the first output. To do that; turn the control AMPERE clockwise until the red LED for current limiting (CC or OL) referring to the output goes off and the green LED for voltage limiting (CV) lights up. Then the VOLT control can be used to adjust the desired output voltage. It is not possible to limit current at the second output, that’s why it has only one control to adjust. By using the pushbutton, the voltage of the second output can be displayed. Simply, hold the button down as long as is wished to see the values on the display.



2.7 Voltalab® 80/10

Measurement unit PGZ402 [RADI68]. Picture 2-5 2.7.1 Purpose of use VoltaLab 80 and its basic version VoltaLab 10 are simple and easy to configure potentiostats PGZ402/100 and electrochemical software VoltaMaster 4 combinations, for recording, analyzing and evaluating of electronic and electrochemical elements. The VoltaLab unit is connected to a PC via the RS232 interface port. 2.7.2 Available settings Voltalab has the software GUI VoltaMaster 4. VoltaMaster 4 v7.08 is an easy configurable measurement sequence editor. It gives the possibility to monitor the detected response signal in real time and record these values in data tables. It has a huge amount of possible configuration settings to measure and evaluate circuits connected to the system. Voltammetry, amperometry and coulometry are only some examples of the methods, which Voltalab can be used for. The program VoltaMaster 4 has also the ability to show the captured data in graphs, apply filters, and change parameters to highlight information.



GUI interface of the VoltaMaster 4. Picture 2-6 Some technical data of PGZ402 [RADI68]: Specifications Working range Maximum compliance voltage ±30V Maximum current output ±1A Maximum polarisation voltage ±15V A/D converter 16bit Measurement period 500µs Max. scan rate 20V/s Max. frequency 100kHz Min. frequency 1mHz Dynamic Impedance Driven up to 100mV/s Static manual & Static auto up to 1V/s Feedback manual & Feedback auto up to 20V/s

Specifications cable of the PGZ402. Table 2-4

The next graph shows an example measurement at a 10MΩ resistor. For this measurement one side of the resistor is connected to the WORK-input of the PGZ402 and the other side is connected to the REF- and the AUX-input. The



voltage-current V-I curve is absolutely linear and there are no visible jumps between the measurement ranges. [WIES03]

Measurement of a 10MΩ resistor with the PGZ402 unit. Graph 2-4 OPEN CIRCUIT POTENTIAL:

The Open Circuit Potential corresponds to the WORK potential measured versus the REF potential. As the name of the measurement method implies the circuit is open so there is no current to flow and measure. A measuring sequence of 30 seconds is enough to calibrate to a drift threshold near zero.

Available settings for Open Circuit Potential measuring method. Picture 2-7



POT. CYCLIC VOLTAMMETRY

Cyclic voltammetry sweep the potential at a given rate and measure the current. The curve obtained is known as a "voltammogram", where voltage to current values are plotted. A ranging for current measurement is available depending on the scan rate.

Available settings for Pot. Cyclic Voltammetry measuring method. Picture 2-8 PULSE - CHRONO POTENTIOMETRY

The WORK potential is measured versus the REF potential while the current is maintained at a pre-set value.

Available settings for Chrono Potentiometry measuring method. Picture 2-9



PULSE - CHRONO AMEPEROMETRY

The current flowing from REF to WORK is measured while the potential between them maintained at a pre-set value.

Available settings for Chrono Ameperometry measuring method. Picture 2-10 IMPEDANCE - POT. FIXED FREQ. EIS (CAPACITANCE)

The WORK potential versus REF is imposed and the electrochemical impedance is recorded at one fixed frequency with an AC signal. A real time plot displays Zimaginary and Zreal versus potential.

Available settings for Pot. Fixed Freq. EIS (Capacitance) measuring method. Picture 2-11



2.8 Sensor chips In this assay, we have two kinds of chips to probe. Both chips have the same kind of sensors, which are temperature, Clark, IDES, ISFET and O2-FET sensors. The first produced chip lot was manufactured at Micronas AG. We refer to this lot with the name cMOS. The second was produced at the Lehrstuhl für Medizinische Elektronik and we name it nMOS. Although both chips are in cMOS technology and in nMOS channel structure, we select this notation from its development history. At the early stages, sensors were made on glass chips, and then came out the silicon cMOS compatible production technology, and with the next design, it has been more specifically so it is called nMOS referring to the n channel structure on a p-substrate. It is not to mix up with the cMOS and nMOS pair, where it refers to digital circuit design. The following short compression can be useful to know more about the components on the both sensor chips: cMOS nMOS

Chip reservoir d=6mm

A=28mm² V=7µL

Chip board 68 contacts A=24x24mm²

Die area A=12.5x14.5mm² A=7.5x7.5mm² TD 1 CLARK (Work electrode)

d=35µm A=960µm²

IDES A=~3mm² A=10.2mm²

ISFET 3x (+4x O2-FETs) AGate=100x3µm²

4x (+2x O2-FETs) AGate=100x10µm²

CV/O2-FET 4x ANME=2096µm²

2x ANME=2600µm²

REF-FET not available 1x

Fast compare between cMOS and nMOS chips. Table 2-5



2.8.1 cMOS

The cMOS chip and its sensors. Picture 2-12 The cMOS chips have the following objects:

a. Temperature sensor: Using a temperature diode (TD). b. Adhesion sensor: One IDES with a contact area of about 3mm². c. Electrode: Metal electrode made of palladium. d. pH value sensors: 7 ISFET sensors including the sensors of 4 O2-FETs. e. Dissolved oxygen sensors: 5 Clark type sensors and 4 O2-FET sensors.

The used sensor chips for this project have the names u01, u02 and u03. All are from the same batch and were examined under microscope for visual noticeable production errors on the chip surface before beginning of the measurements. The examination under microscope is repeated casually to prevent any measurements may interpreted mistakenly and falsify the results.

1mm


- 28 - Characterization of

Pins assignment (not true to size). Picture

PIN Chip cMOS1 ISFET A

O2/CV-2 3 ISFET B4 5 Temperature diode6 7 ISFET C8 9 ISFET D

of miscellaneous multi parametrical silicon based bios

Pins assignment (not true to size). Picture 2-13

Chip cMOS Connector ISFET A

-FET A Drain

Source

ISFET B Drain Source

Temperature diode Cathode Anode

ISFET C Drain Source

ISFET D Drain

biosensor chips



10 Source 11 Substrate x1 Sub x1 15

ISFET E O2/CV-FET 1

Source 16 NME 18 Drain 17 ISFET F

O2/CV-FET F Drain 20

Clark sensor Working electrode

22 Auxiliary electrode 24 Reference electrode 23 ISFET F

O2/CV-FET F NME 25

Clark sensor 2 Working electrode

26 Auxiliary electrode 27 Reference electrode 28

IDES

Anode 29 Anode 2 31 Cathode 32 Cathode 2 30 ISFET F

O2/CV-FET F Source 33

Clark sensor 3 Auxiliary electrode

34 Working electrode 35 Reference electrode 36 Substrate x2 37 Reference electrode 38 Substrate x3 Sub x3 50


51 Reference electrode 53 Auxiliary electrode 52 Substrate x4 54 Clark sensor 5 Working electrode 55 Reference electrode



57 Auxiliary electrode 56

ISFET G O2/CV-FET G

NME 58 Source 59 Drain 60 ISFET A

O2/CV-FET A NME

Pins assignment of the pin box. Table 2-6

Pin numbers within yellow colored cells means that numbered pin, which belongs to a sensor, does not exist on the pin box output. (See “Pin box” chapter 2.9 on page 34) 2.8.2 nMOS

The nMOS chip and its sensors. Picture 2-14

1mm



The nMOS chips have the following objects:

a. Temperature sensor: Using a temperature diode (TD). b. Adhesion sensor: One big IDES with a contact area of about 10mm². c. pH value sensors: 6 ISFET sensors including the sensors of 2 O2-FETs. d. Dissolved oxygen sensors: A single Clark type sensor and 2 O2-FET

sensors. The used sensor chips for this project have the names f5, f8, i5 and c10. All are from the same batch and were examined under microscope for visual noticeable production errors on the chip surface before beginning with the measurements. The letter in the name of the sensor chip corresponds to the horizontal placing the sensor chip on the wafer, and the number after it is for the vertical place.

The sensor chips on the nMOS 4 inch wafer. Picture 2-15 The examination under microscope is repeated casually to prevent any measurements may interpreted mistakenly and falsify the results.



Pins assignment (not true to size)[WIES05]. Picture 2-16

PIN Chip nMOS Connector 1 ISFET A Drain 2 Source 3 ISFET B Drain 4 Source 5 Temperature diode Cathode 6 Anode 7 ISFET C Drain 8 Source 9 ISFET D Drain

10 Source 11 Substrate x1 Sub x1 15 ISFET E Source



16 O2/CV-FET 1 NME 18 Drain 20

Clark sensor Working electrode


IDES

Anode 29 Anode 2 31 Cathode 32 Cathode 2 63

ISFET E O2/CV-FET 2

Drain 64 NME 65 Source 66

REF-MISFET Drain

67 Gate 68 Source

Pins assignment of the cMOS chips. Table 2-7

ISFET E has no contact pin for its source contact on the pin box output. Therefore it is colored in the table with yellow.



2.9 Pin box

Picture of the used pin box. Picture 2-17 2.9.1 Purpose of use The pin box is an adaptor, which converts the contact pins from the base of the sensor chip board using a PLCC68 socket to BNC connector type. The BNC is an isolated connector type used widely by most of measuring units in labs. The case has ports for 48 lines including a connector for the grounding of the aluminum case. Although the PLCC68 socket has 68 contacts, which is more than the available outputs connector on the pin box, there is no need to have all the 68 pins of the socket to have BNC outputs. That’s because the sensors on the chip need only a maximum of 46 lines to operate.



2.9.2 Available connectors

PIN Chip cMOS Chip nMOS Connector 1 ISFET A

O2/CV-FET A ISFET A Drain

2 Source 3

ISFET B ISFET B Drain

4 Source 5

Temperature diode Temperature diode Cathode

6 Anode 7

ISFET C ISFET C Drain

8 Source 9

ISFET D ISFET D Drain

10 Source 11 Substrate x1 Substrate x1 Sub x1 13 14 15

ISFET E O2/CV-FET 1

ISFET E O2/CV-FET 1

Source 16 NME 18 Drain

17 ISFET F O2/CV-FET F Drain

19 20

Clark sensor Clark sensor Working electrode


23 ISFET F O2/CV-FET F NME

25 Clark sensor 2

Working electrode 26 Auxiliary electrode



27 Reference electrode 28

IDES IDES

Anode 29 Anode 2 31 Cathode 32 Cathode 2

30 ISFET F O2/CV-FET F Source

33 Clark sensor 3

Auxiliary electrode 34 Working electrode 35 Reference electrode 36 Substrate x2 37 Reference electrode 38 Substrate x3 Sub x3 39 40 41 42 43 44 45 46 47 48 49 50


51 Reference electrode 53 Auxiliary electrode 52 Substrate x4 54


55 Reference electrode



57 Auxiliary electrode 56

ISFET G O2/CV-FET G

NME 58 Source 59 Drain

60 ISFET A O2/CV-FET A NME

61 62 63

ISFET E O2/CV-FET 2

Drain 64 NME 65 Source 66

REF-MISFET Drain

67 Gate 68 Source

grounding

Pins assignment of the nMOS chips. Table 2-8

Pin numbers within yellow colored cells means that numbered pin does not exist on the pin box output. Empty yellow cells are pins which does not have corresponding sensor on the chip.



2.10 Non-Semiconductor sensors Non-Semiconductor sensors are the ones which are on the surface of the chip and have no contact with the silicon semiconductor layer. Clark and IDES sensors are produced by silicon technology using metallization and oxidation, but they are isolated with an oxide layer from the silicon. 2.10.1 Clark sensor (Amperometry) 2.10.1.1 Idea Voltammogram is applying a voltage ramp to an electrolyte to determine a voltage region where voltage is essentially independent of current. A typical voltammogram of aqueous solutions e.g. PBS in range of 0 to -1.4V has several regions. These regions vary according to dissolves substances in the solution. The regions of a solution, which is with oxygen dissolved, can be illustrated and explained as fallowing. [BRIS06]

Typical voltammogram of Clark sensor. Graph 2-5



REGION I (ZERO CURRENT REGION): The voltage U is not enough to reduce molecules at the work electrode. The current there is almost zero.

REGION II (INTERMEDIATE REGION):

The ability of the oxygen molecules to pass the electrochemical double layer (inner and outer Helmholz plane) to the work electrode limits the current.

Cause of diffuse current of dissolved oxygen [ISRA07]. Picture 2-18 REGION III (PLATEAU REGION):

Transport of oxygen molecules to the work electrode is causing a diffusion current, which is relative to the concentration of oxygen in the electrolyte solution. ∝ . This is limited to current. The width of the region is dependent on the diffusion of the oxygen molecules. This can be explained with Fick's first law, which is used in steady-state diffusion, i.e., when the concentration within the diffusion volume does not change with respect to time.



= −

Diffusion flux. Equation 2-7

Where: D is the diffusion coefficient or diffusivity,

is the concentration of oxygen in the solution, x is the position.

And the electrical current caused by diffusion is =

Diffusions current. Equation 2-8

Where: n is the number of free transported electrons.

F is the Faraday constant. A is area of the cross section. x is the position.

is the diffusions flux. In addition, using Laplace transformation we get[BARD00]: ( ) = √ ∗√

Diffusion Current respect to time t. Equation 2-9

For current after a long time and a temperature of 25°C, it can be simplify to: = 4

Oxygen concentration current. Equation 2-10

Where r is radius of the work electrode.[MUGG02]



REGION IV (DISSOCIATION REGION): Over potential dissociates water molecules. This is visible by the hydrogen formation in gas form. Solutions without dissolved oxygen have almost this region only.

2.10.1.2 Equipment and items VOLTALAB 80:

Voltammetry - Pot. Cyclic Voltammetry:

To get a curve we use a potential ramp as input parameter and read the current response of the Clark sensor, in the range of zero to -1.4V. To avoid current flowing through the reference electrode, we use an auxiliary electrode.

PIN BOX ASSIGNMENT:

Sensor No.

Auxiliary electrode

Working electrode

Reference electrode

4 22 20 24

Pins assignment of the Clark sensor. Table 2-9

Sensor number 4 on cMOS chips has the same contact pin numbers as the single sensor on nMOS chips.

SOLUTIONS:

- PBS: Phosphate buffered solution with pH value of 6.5 with from air dissolves oxygen. The oxygen saturation in PBS has a concentration of 7.8811mg/l or 0.25mM.

- Calibration solution: Na2SO3 (M=126g/mol) added as 1g to 100ml PBS, enough to bind the oxygen molecules in the PBS solution.



2 + → 2

Chemical reaction to bind dissolved oxygen. Equation 2-11

SERSOR CHIPS

Clark sensor on the cMOS chip. Picture 2-19

Clark sensor on the nMOS chip. Picture 2-20 Working electrode is circle shaped and has diameter of 35µm on both chips. The auxiliary and reference electrodes are surrounding the working electrode in ring form. The reference electrode is as big as about one third surface area of the auxiliary electrode. On the cMOS chips, this ring is directly surrounding the electrode. On the other side, the ring of the nMOS chip has a distance of about 250µm from the working electrode.

1mm 250µm

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1 2

3 4 5 1mm 250µm

RReeffeerreennccee eelleekkttrrooddee WWoorrkkiinngg eelleeccttrrooddee AAuuxxiilliiaarryy eelleeccttrrooddee



The nMOS chip has only one Clark sensor, where the cMOS has 5 Clark sensors. The single sensor of the nMOS has the same contacts of the sensor number 4 on the cMOS chips. 2.10.1.3 Measurement assembly

Schematic design of the measuring system. Picture 2-21

Measurement assembly. Picture 2-22



2.10.1.4 Measurement settings and parameters

- To reduce capacitive effects caused by polarization slower scan rates are to be chosen, in this case 10 / .

An example for a voltammogram voltage. Graph 2-6

- By PBS the disassociation of the water within it begins already below −1.4 , so no need to scan more than this value.

- is in around −10 . Therefore, the range of the measured current must be within ±1µ , otherwise the Voltalab unit -due the change to a smaller accuracy range- will not be able anymore to detect small currents in nA range

- The influence of the temperature is to ignore, due the small effect of the temperature on the diffusions constant, which is under 2%.[HITC78].

- The diffusions constant D is an exponential function of temperature T: =

Diffusions current. Equation 2-12

Where: is the diffusions constant at a reference temperature, is the activation energy for diffusion,

R is gas law constant.



2.10.1.5 Procedure

1. Making several cycles at higher scan rate using the setting explained in the previous chapter will deliver more accurate results.

2. Repeating the measurement again with the same parameters but this time

using a PBS solution without oxygen dissolved in it.

3. Choose an operation point from the tableau region with significant difference between the measurement with and without oxygen.



2.10.2 IDES Sensor (Impedimetric) 2.10.2.1 Idea An electrochemical half cell consists of the resistance of the electrolyte solution, the capacity of the electrochemical double layer q.v. Clark sensor (Amperometry) and the resistance of the charge transfer. Using impedance measurement we can calculate the imaginary component as like capacity and the real component as the resistance. In order to determine impedance, complex Ohm’s law is used: = ( ) ( )

Complex Ohm’s law. Equation 2-13

For impedance measurement, a two-wire electrical measurement assembly is used. However, when the impedance to be measured is relatively low, or the impedance of the probe is relatively high, a 4-point probe measurement will yield more accurate result. TWO-WIRE MEASUREMENT METHOD:

A known alternating voltage at a defined frequency is applied across the unknown impedance Z. This voltage source is alternating symmetric at zero volts and it should not generate a current. In other words, the voltage source must have a high resistance at chosen frequency. The current that flows through the probe is measured. The impedance can then easily determined by dividing the applied current by the measured current.

An ideal circuit for measuring an impedance Z. Picture 2-23



The measurements done with two-wire setup include not only the impedance of the electrolyte but also the impedance of the leads and contacts. This may be a problem falsifying the results. When using an impedance meter to measure values above few ohms or picofarads, this added small impedance is usually not a problem. However, when measuring low impedances or when contact and lead resistance and capacity may be high, obtaining accurate results with a two-wire measurement may be problematical.

Realistic circuit incl. interfering components. Picture 2-24

FOUR-WIRE MEASUREMENT METHOD:

A solution for the problem of two-wire measurements is using the four-wire measurement setup. Because a second set of probes are for sensing and since the current I0 though the electrolyte is negligible small, only the voltage drop across the device under test is measured. As a result, impedance measurement is more accurate.

Four-wire impedance measurement circuit. Picture 2-25




Pot. Fixed Freq. EIS (Capacitance):

To measure the impedance, an alternating sinus voltage is applied and the resulted current is measured.

PIN BOX ASSIGNMENT:

Sensor Anode Anode No. 2 Cathode Cathode No. 2 IDES 28 29 31 32

Pins assignment of the IDES sensor. Table 2-10

SOLUTIONS:

- De-ionized water. - PBS: Phosphate buffered saline solution. It has a molar concentration

of about 150mM of NaCl. - PBS solutions with 75, 225, and 300mM of NaCl. -

SERSOR CHIPS

- nMOS chips have a visible sensor area of about A=8mm², while cMOS chips have about one third of it.

IDES sensor on the nMOS chip. Picture 2-26

2mm



IDES sensor on the cMOS chip. Picture 2-27 The nMOS chip has a polygon shaped IDES and it covers almost the half visual area of the fluid contact surface. The IDES on the cMOS is much smaller and rectangular. On the both of the chips, the IDES sensor is placed centered and the other sensors types is surrounding it. 2.10.2.3 Measurement assembly


The impedance measurement assembly is good enough to achieve clear results using the two-wire method. The Voltalab and the isolated BNC cables have insignificant effect on the measured values, due its low electrical resistance and capacity.

1mm



2.10.2.4 Measurement settings and parameters To measure the impedance, a voltage of 30mV with a frequency of 10kHz is applied and the resulted current for 20 seconds is measured.

AC signal for impedance acquisition. Graph 2-7 The applied sinus voltage is alternating at zero with an enough frequency to avoid current flow.

Influence of frequency on impedance[BRIS06]. Graph 2-8



Using Ohm’s law the impedance can be easily calculated and plotted in real and complex components. = + = + = ( ) = ( ) = 2

Real and complex component of impedance. Equation 2-14

2.10.2.5 Procedure

1. Making several cycles using the setting explained in the previous chapter with a PBS solution of 75mM NaCl.

2. Repeating the measurement again with the same parameters but this time using PBS solutions with steps of 75mM to 300mM.

3. The resulted measurements should be vary in real component.



2.11 Semiconductor sensors Semiconductor sensors are in contrast to the non-semiconductor sensors have structures within the silicon semiconductor layer. Temperature diode, ISFET and CV/O2-FET all share the silicon layer with different doped regions. 2.11.1 Temperature Diode (Potentiometry) Temperature change effects the properties of semiconductors, and this will falsify the measurements. Therefore sensors falsified by temperature must be adjusted with a correction factor relatively to the temperature. When using living cells the cell activity is temperature dependent. 2.11.1.1 Idea The characteristic curve of a p-n diode shows a direct temperature dependency. This can be explained with the electronic band structure model. Operating such a diode with a current in forward bias and a voltage , gives us Schockley’s diode law [MSZE98]: = ( − 1) Schockley’s diode law. Equation 2-15

For ≫ = Schockley’s simplified diode law. Equation 2-16

Where: is the thermal diode current,

is the saturation current, is the voltage across the diode, is the thermal voltage.

The diode equation in respect of voltage can be written as:



=

Diode law in respect to voltage. Equation 2-17

The thermal voltage UT is a known constant defined by: =

Thermal voltage. Equation 2-18

Where: q is the magnitude of charge on an electron (elementary charge),

k is Boltzmann’s constant, T is the absolute temperature of the p-n junction in kelvins.

So is approximately 26 mV at room temperature of 300K. [MOHR00]. The voltage change is −2.25 / in the range from −50° to +150°C. [STEP06].

I-V characteristic curve of a diode and the influence of temperature. Graph 2-9



2.11.1.2 Equipment and items INCUBATOR:

For a constant and adjustable environment temperature.

VOLTALAB 80:


To get a diode curve we use a potential ramp as input parameter and read the current response of the diode, in the range of zero to 3V.

Pulse - Chrono Potentiometry:

At chosen fixed work current we measure the voltage as a function of the temperature change.

PIN BOX ASSIGNMENT:

Sensor cathode Anode TD 5 6

Pins assignment of the temperature diode. Table 2-11

SERSOR CHIPS

Temperature diode on the cMOS chip. Picture 2-29

1mm 15µm



Temperature diode on the nMOS chip. Picture 2-30 The diode on the nMOS chip has a remarkable bigger area than the pn diode of the cMOS. This will cause different behavior for the temperature dependency. The pn diode is isolated with the protection layer and therefore it has no direct contact to the electrolyte. This makes the temperature sensor electrolyte independent, so there is no aging caused by contacting with fluids. 2.11.1.3 Measurement assembly

Schematic design of the measuring system. Picture 2-31 For fast tests, fluids with different temperatures can be used instead of the incubator. But characterizing and long term measurements are not possible due

1mm 30µm



the small amount of the fluid (7µl), which has a smaller heat capacity than the sensor chip. So, the fluid will get the temperature of the chip in a short time. 2.11.1.4 Measurement settings and parameters A diode characteristic curve is U-I curve. That means we measure the current in dependence on the applied voltage. Instead of choosing voltage as an operation point and measuring its current, we set a current as operation point and measure it’s correspond voltage. That is because the voltage is easier and more accurate to measure using a simple electrical circuit than measuring a current. The supplied current can be easily generated with a voltage to current amplifier circuit. 2.11.1.5 Procedure

1. Make a fast test to determine the resulted current range within a voltage from zero to 3 volts. Our target is to get smallest current as an operation point. A higher current causes more internal heating of the diode, which is not only falsifying the real temperature of the sample, but it can also rise its temperature to unwanted values especially for living cells.

2. At room temperature, measuring the current for a given voltage ranging

from zero to maximal 3 volts, and repeat it at higher temperatures. It’s not to forget, that in the course of the day, the room temperature can be vary according to the sunlight, operating of electrical equipment and the number of persons sharing the same room. All this produce extra heat in the room and may cause to bias the results. So using an incubator with a temperature a little above room temperature will give a more clear result without having temperature variations when measuring. 27°C seems to be easy to realize and keep constant by the incubator. The used incubator needs about an hour to heat up and to remain at a constant temperature, and another one after reaching the target temperature, to let the sensor chips and its terminal box also to reach this temperature.

3. Determining the best operation point, at lowest current with significant

temperature influence. This can be done easy by reversing the voltage-current U-I curve to current-voltage I-U curve and selecting the biggest voltage range at the same current.



2.11.2 Reference MISFET (nMOS) 2.11.2.1 Idea

MISFET [HENN05]. Picture 2-32 A MISFET is an active part. It works like a voltage controlled resistor. It has three ports (electrodes): Gate, Source and Drain. As basic material a low p doped silicon substrate is used. In this substrate two high n doped regions are embedded. These two regions make the drain and source ports. Between these two regions there must be a p doped region so we get an npn structure. Though this npn flows for now no current, because it is like a np diode which is connected afterwards with a pn diode. When the first diode allows flowing current through it, the second one will block it. Above the p doped region, which is between the n regions, is an isolation layer and then a metal layer. This construction builds the gate port.



By applying a potential at the gate port, an electrical field is created, which creates within the embedded p region an n electrons channel. The size of this channel is proportional to the gate potential.

Source-drain current. Graph 2-10, Picture 2-33 Usually source and drain pins are interchangeable, but the manufacturing may be not made symmetric. The MISFET has three operation modes:

CUT-OFF, SUB-THRESHOLD OR WEAK INVERSION MODE:

This operation mode is when the gate-source voltage UGS smaller than threshold voltage of the device Uth. The transistor is turned off. This means there is ideally no current flows through the transistor, because there is no conducting n-channel between source and drain. In reality, the Boltzmann distribution of electron energies is allowing some electrons at the source to enter the n channel and flow to the drain. This results in a sub-threshold leakage current.



LINEAR/OHMIC REGION OR TRIODE MODE:

This operation mode is when the gate-source voltage UGS bigger than the threshold voltage Uth and drain-source voltage is smaller than the difference between source-gate UGS and threshold Uth voltages. The transistor is turned on. This means, that the n channel between the drain and source has been created: This allows current to flow through the transistor. The MISFET operates in this mode like a controllable resistor. This can be done by the gate voltage. This current has also dependency on the gate’s width and length and the isolating layer electrical capacity

SATURATION MODE OR ACTIVE MODE:

This operation mode is when the gate-source voltage UGS is bigger than the threshold voltage Uth and drain-source voltage is bigger than the difference between source-gate UGS and threshold Uth voltages. The transistor is turned on. This means that the n channel between the drain and source has the maximal capacity, which allows current to flow through it. The drain current is now weakly dependent upon drain voltage and controlled primarily by the gate-source voltage.



To get the characteristic curve of the ISFET we use a potential ramp as input parameter and read the current response.

VOLTAGE SOURCE: Applying several voltages on the gate port, to control the current between source and drain.

PIN BOX ASSIGNMENT:

Drain Gate Source REF-

MISFET 63 64 65




SERSOR CHIPS

Chip No. of sensors Gate area nMOS 1 3x100µm² cMOS 0 n/a


The reference transistor is identical in contraction to the ISFET sensor, which is described and evaluated in the next chapter. The characteristic curves of the reference are in the same range of the ISFET. So a malfunction of the reference is a good indicator for the malfunction ISFET, without using any fluids to test.

Reference MISFET on the nMOS chip. Picture 2-34 Above is a picture of the die. The MISFET is located in the top right corner of it. The transistor can be seen only before the packaging. The package for the protection of the bonding and the plastic fluid reservoir above it covers the transistor completely.

1mm 100 µm



2.11.2.3 Measurement assembly


No need for fluids to operate the reference transistor. Transistors have temperature dependency, so operating the transistor for a long time may cause to heat and that will effect the measuremesnt. Using fluid can make the transistor heating being less, and that’s by taking some heat from the surface of the chip to the fluid. 2.11.2.4 Measurement settings and parameters

For the characteristic curve of the reference MISFET, the used potential ramp of the UDS is in the range of 0V to 5V. The UGS is in 1V steps from 0V to 5V.

2.11.2.5 Procedure

1. Measuring IDS while applying UDS in a ramp from 0 to 5V. The power supply is not yet connected the gate port.

2. Repeating the measurement of IDS while increasing USG in 1V steps from

0V to 5V.



2.11.3 ISFET Sensors for pH-Measurement 2.11.3.1 Idea The pH of a solution is dependent on the concentration of hydrogen ions or its correspondent hydroxide ions. The higher is the concentration of hydroxide ions in a solution, the higher is its pH value. = −log [ ] = 14 − = 14 + log [ ] ∆ ( ) = − log [ ( )] = 14 + log [ ( )]

pH value dependency on the concentration of . Equation 2-19

ISFET has an ion sensitive layer. On this layer the gathering ions create a potential. This potential is the ISFET controlling potential of gate. The n-channel within the semiconductor of the ISFET is established and allows the current to flow though the transistor from source to drain. The higher is the gate vs. source potential, the wider is the n-channel and higher is the current flow from source to drain.

Effect of the hydroxide on the source drain current. Graph 2-11, Picture 2-36




Voltammetry - Pot. Cyclic Voltammetry: To get the characteristic curve of the ISFET we use a potential ramp as input parameter and read the current response.

Pulse - Chrono Potentiometry: At chosen fixed work current we measure the voltage as a function of the pH change.

PIN BOX ASSIGNMENT:

Drain Source ISFET A 1 2 ISFET B 3 4 ISFET C 7 8 ISFET D 9 10 ISFET E 18 15

Pins assignment of the ISFET sensors. Table 2-14

ISFET E is also in the same time an O2-FET with a surrounding NME.

SOLUTIONS:

- PBS: Phosphate buffered saline solution with a pH value of 7.3 - A seconds PBS solution with a pH of 6.8.

REFERENCE ELECTRODE:

- Ag-AgCl electrode.



SENSOR CHIPS

ISFET sensor 4 on the cMOS chip. Picture 2-37

ISFET sensor on the nMOS chip. Picture 2-38 The placing of the ISFET sensors on both chips is different. While the sensors on cMOS chip are evenly distributed on the chip surface, the ones of the nMOS chip are on the both sides of the IDES sensor, which is located in the middle of the chip.

GGaattee DDrraaiinn SSoouurrccee

1mm 100µm

GGaattee DDrraaiinn SSoouurrccee

1mm 100µm




Measurement assembly of the project. Picture 2-39

The power supply seen in the picture above is used experimentally to raise the gate voltage by raising the reference potential. q.v. “Loosing of the passivation layer” in chapter 4.2 on page 100.




The reference electrode can be connected to the source line. But we made the measurements by connecting the reference electrode with the ground. The current (IR) is insignificant small. 2.11.3.4 Measurement settings and parameters

For the characteristic curve of the ISFET the used potential ramp is in the range of -3 to 3V. At chosen fixed work current we measure the voltage as a function of the pH change. This voltage must be under 3 volts, and it is recommended to choose a working point with a corresponding voltage of 2.5V.

2.11.3.5 Procedure

1. First we need to plot the characteristic curve of the ISFET. This can be easily realized with applying a voltage ramp from 0 to 3V, and record the measured current of the current from drain to source. The reference electrode is connected to ground. The measurement assembly must be isolated within a faraday cage. We repeat this step with various ph valued solutions of pH7.3 and pH6.8. The curve must be differing to the one with a different ph value.

2. From the graph of characteristic curve we can choose a working point current, which has corresponding voltage below 3V and covers the pH range we measured pH7.3 and pH6.8.

3. At the chosen working point current we repeat the measurement and we

record the resulted voltage. This voltage change is a corresponding to pH change.

4. The voltage change per pH value or the sensitivity can be easily read

from the voltage run curve. Where pH the pH value change amount between cal and mes solutions.

= ∆ or its equivalent = ∆

pH measuring sensitivity in voltage per pH . Equation 2-20



2.11.4 O2-FET Sensors for DO-Measurement 2.11.4.1 Idea A noble metal electrode (NME), which is surrounding an ISFET sensor, can convert the dissolved oxygen into hydroxide by applying a reduction potential of -600mV against a reference electrode. The produced hydroxide from the NME increases the electrical potential of the gate region on the ISFET sensor. The gate potential controls the voltage between source and drain of the transistor. This voltage is negative proportional to the pH value. + 2 + 4 ⎯⎯⎯⎯⎯ 4 ( )

Reduction of dissolved oxygen. Equation 2-21

Where ( ) is the hydroxide, which is reduced from the dissolved oxygen DO.




The difference in the pH value change between 0 and -600mV comparing to a solution without dissolved oxygen (calibration solution) is a scale for the dissolved oxygen (see the graphic below). pH value changes can be measured easily by the ISFET sensor. ∆ ( ) = −log [ ( )] = 14 − ( ) = 14 + log [ ( )] [ ] ∆ ( )

pH change depending on oxygen reduction. Equation 2-22

Where c[ ( )] is the concentration hydroxide, which is reduced from the dissolved oxygen. 2 ↔ +

Hydroxide and hydronium ions from water. Equation 2-23

There are 2 pH values when measuring. The first one is the DO-independent pH. And the second is the DO-dependent pH(DO). The DO-independent pH difference between calibration and measuring solution: ∆ = ∆ (0 ) = @ − @

or = −

pH measurement without reduced hydroxide. Equation 2-24

Where cal is the calibration medium with no dissolved oxygen and mes is the measuring target solution with the dissolved oxygen. For continuous long time measurements the global drift cannot be ignored.



Run of the curves of the PBS with and without dissolved oxygen. Graph 2-13 The pH change, which is only dependant on the reduced oxygen, can be defined as: ∆ ( 2) = ∆ ( ) − ∆ ( )

where ∆ ( ) = @ − @ and ∆ ( ) = @ − @

Calculating pH change due oxygen reduce. Equation 2-25


Voltammetry - Pot. Cyclic Voltammetry: To get the characteristic curve of the ISFET as a proof of functionality of the pH measurement we use a potential ramp as input parameter and read the current response.



Pulse - Chrono Potentiometry: At chosen fixed work current we measure the voltage as a function of the pH change.

VOLTALAB 10:

Pulse - Chrono Ameperometry: The NME can reduce dissolved molecules in the electrolyte solution e.g. dissolved oxygen molecules into hydroxide, and that by applying a specific reduction potential against a reference electrode. The current resulted is proportional to the amount of the reduced ions by the NME.

PIN BOX ASSIGNMENT:

Sensor No Drain NME Source O2-FET E 15 16 18

Pins assignment of the O2-FET sensor. Table 2-15

Only sensor O2-FET E has the same on both of the chips, and the only one which has contacts pins on the pin box. Because of that the other sensors are ignored.

SOLUTIONS:

- PBS: Phosphate buffered solution with pH value of 6 and 8 saturated with oxygen from air as 7.8811mg/l or 0.25mM.

- A seconds PBS solution with a pH of 8. - Calibration solution: Na2SO3 (M=126g/mol) added as 1gr/100ml PBS.

This calibration solution has a pH value of about 8. REFERENCE ELECTRODE:

- Ag-AgCl electrode for the NME. - Ag/AgCl electrode in 3M KCl solution for the ISFET, to avoid current to

flow though the electrode and then to the electrolyte. Because of that, the ISFET reference is galvanically isolated from the NME electrode



SERSOR CHIPS

No. of sensors NME area Gate dimension cMOS 4 2096µm² 100×3 µm² nMOS 2 2600µm² 100×10 µm²

Compare between O2-FET sensors of the cMOS and nMOS chips. Table 2-16

ISFET sensor on the cMOS chip. Picture 2-42

ISFET sensor on the nMOS chip. Picture 2-43 The platinum electrode is surrounding the gate area of a usual ISFET sensor. CMOS has 4 O2-FETs, while nMOS has only 2. Only one O2-FET sensor on each chip has the same pin order as the other one. It labeled as O2-FET1 and ISFET E.

1mm 100µm

DDrraaiinn GGaattee SSoouurrccee

NNMMEE

1mm 100µm

DDrraaiinn GGaattee SSoouurrccee

NNMMEE






For the characteristic curve of the ISFET the used potential ramp is in the range of -3 to 0V. At chosen fixed work current, the voltage is measured as a function of the pH change. This voltage must be under 3 volts, and recommended to choose a working point with a corresponding voltage of -1.5V. As alternative, the current can be measured as a function of the pH change. On the NME side, dissolved oxygen molecules are reduced into hydroxide by applying a potential of -600mV against its reference electrode. The current IL resulted is proportional to the amount of the hydroxide reduced by the NME. For oxygen saturated PBS solution this current is around 10µA for every mm² surface area of the NME.



2.11.4.5 Procedure

1. To plot the characteristic curve of the ISFET, a voltage ramp from 0 to 3V is applied, and the current from drain to source is recorded. The reference electrode is connected to ground. The measurement assembly must be isolated within a faraday cage. This step must be repeated with various pH valued solutions as pH 6 and pH 8 and then compared with an electrolyte solution without dissolved oxygen. The curves must be differing to each other as shown in the last graph.

2. We repeat the last step with applying an NME voltage of -600mV.

3. From the graph of characteristic curve we can choose a working point current, which has corresponding voltage below 3V and covers the pH range we measure between pH6 and pH8. The measured currents must be greater than zero so the dissolved oxygen can be read from it.

4. At the chosen working point current we repeat the measurements and we

record the resulted voltage. This voltage change is corresponding to pH and DO change.

5. The concentration of DO of an electrolyte vs. the maximal DO concentration of the electrolyte which it can have from the air is [ ] = ∆ ( ) ∆ ( )

Percentage of DO content in a measuring electrolyte. Equation 2-26



2.11.5 CV-FET (an extended O2-FET Sensor) 2.11.5.1 Idea As described in the last chapter the ISFET measures the potential caused by reducing the dissolved oxygen molecules to hydroxide by applying a voltage of −600 . Other substances, which deliver hydroxide or hydrogen ions by reducing, can be used instead oxygen. The reducing voltage must be below the dissociation voltage of water. 2 . ⎯⎯⎯⎯⎯ + 2

Dissociation of water. Equation 2-27

Instead of producing hydroxide ions OH-, the consumption of the hydronium ions H3O+ from the electrolyte can be also used. The general chemical equation can be written as: + + . . ⎯⎯⎯⎯⎯⎯ +

Reducing of dissolved XO. Equation 2-28




To confirm this we added MnO4- ions to PBS solution by dissolving KMnO4 in it. This solution has the same pH value as the PBS, so the difference in measured values while applying reducing voltage is a sign for the consumption of the hydronium ions. This will cause to increase the pH value by the ISFET. + 5 + 8 . . ⎯⎯⎯⎯⎯⎯ + 12

Reducing of dissolved MnO4-in PBS. Equation 2-29


For the characteristic curve of the ISFET the used potential ramp is in the range of -3 to 0V. At chosen fixed work current, the voltage as a function of the pH change is to measure. This voltage is to be under 3 volts, and it is recommended to choose a working point with a corresponding voltage of -2.5V. As alternative, the current as function of the pH change can be measured. On the NME side, molecules are reduced into hydroxide by applying a potential against its reference electrode. The current IL resulted is proportional to the amount of the hydroxide reduced by the NME.

2.11.5.3 Procedure

1. To plot the characteristic curve of the ISFET we apply a voltage ramp from 0 to 3V, and record the measured current of the current from drain to source. The reference electrode is connected to ground. The measurement assembly must be isolated within a faraday cage. We repeat this step with various pH valued solutions as pH 6 and pH 8. The curves must be differing to each other.

2. We repeat the last step with applying an NME voltage.

3. From the graph of characteristic curve we can choose a working point current, which has corresponding voltage below 3V and covers the pH range we measure between 6 and 8. The measured currents must be greater than zero so the dissolved oxygen can be read from it.



4. At the chosen working point current we repeat the measurements and we

record the resulted voltage. This voltage change is corresponding to pH and OH- change.

5. The equations used for O2-FET can be used also here. Simply replacing DO

with the target substance e.g KMnO4.

Results and Discussion


3 Results and Discussion In this chapter, the obtained results for semiconductor and non-semiconductor sensors will be presented. The measured real values will be also compared to the calculated values using the equations and methods explained in chapter three. Any variation of the measured value from the calculated ones will be explained.

3.1 Non-Semiconductor sensors In this chapter the obtained results for Clark and IDES sensors will be presented. The measured values will be also compared to the calculated values. 3.1.1 Clark sensor Bahr [BAHR02] used the equation of the oxygen concentration current for an estimation of the current measured with the oxygen sensors used in his work. At a temperature of 25°C, a saturation concentration in PBS of 7.8811 mg/l or 0.25mM and a radius of 15µm he gets a current of 3nA. This calculation is not accurate. Because the surface is not perfectly even. Therefore, it must be complemented by multiplying with a roughness factor of 2 or 3. = 4 ∗ ( )

Extended oxygen concentration current. Equation 3-1

The higher is the roughness factor of a surface, the bigger is its real area. This effect can be demonstrated with a cross section of a surface, with several roughness factors, in the next figure.



Roughness factor and the length. Picture 3-1 Experimentally, in consideration of the roughness of the electrode surface, the current has to be multiplied with factor two or three. The roughness factor is the ratio between the true electrode area and the geometric electrode area. The true electrode area is the area of the electrode surface, taking into consideration the surface roughness. For a perfectly smooth electrode, it is equal to the geometric electrode area, which is the area calculated from its geometrical dimensions. 3.1.1.1 cMOS chips

Voltammogram curve of the clark sensor on chip u01. Graph 3-1

The used work electrode in this chip has a radius of 17.5µ .

fr = 1

fr = 2 à 2x longer

fr = 3 à 3x longer



The limit current iL is about −11 , that’s almost the same ratio of 0.2 /µ as Bahr has calculated, and then multiplied with factor 3 for its surface roughness. After successfully measurements on several chips, the best choice for an operation point is at −600 . This value is located in the plateau region of all sensors we tested. The plateau region has an average width of 0.6 . 3.1.1.2 nMOS chips

Voltammogram curve of the clark sensor on chip f5. Graph 3-2

Although, the work electrode in this chip has the same radius as the cMOS chips, delivers but less current. This can be explained with the less roughness of the electrode surface comparing with cMOS, thus the estimated value should be multiplied with a roughness factor of 2. The calculated end value is −7 , which is really near to the measured value of −8 . Best operation point for this chip is −600 . The plateau region has an average width of 400 .


- 80 - Characterization of

3.1.2 IDES Sensor NaCl has a molar conductivity of 126.5 Scm²M 3.1.2.1 cMOS chips

Measuring with

3.1.2.2 nMOS chips

Measuring with

225mM300mM

300

325

350

375

400

425

450

475

500

120 145

-Zi [Ω

]

225mM300mM

50

55

60

65

70

75

80

85

90

95

100

44 46 48 50 52

-Zi [Ω

]

of miscellaneous multi parametrical silicon based bios

NaCl has a molar conductivity of 126.5 Scm²M-1 or 7.905Ωcm²mM-1.

Measuring with IDES sensor on chip u01. Graph 3-3

Measuring with IDES sensor on chip f8. Graph 3-4

150mM

170 195 220Zr [Ω]

150mM

54 56 58 60 62 64 66 68 70Zr [Ω]

biosensor chips

75mM

245

75mM

72



Resistance has a reverse dependency on area. The resistance measured with the cMOS sensor is three times bigger than the one from the nMOS. That’s because the nMOS chips have an IDES surface area as big as three times of the one on cMOS chips. The ions in the PBS solution is not only from NaCl but also from its other components like KH2PO4, Na2HPO4 and KCl. Thinning the PBS by 50% with deionized water will result in a solution with 50% less ions. The new solution is including the concentration of NaCl of about 75mM. The 300mM labeled solution is a 300mM NaCl solution and has not exactly the doable quantity of ions in a regular PBS solution with a NaCl of 150mM, for the same reason explained before. The real concentration of all ions is less. The non equal stepping of ion concentration in the solution explains the different distance between the measured point, which is remarkable in the distance before and next to 150mM PBS.



3.2 Semiconductor sensors In this chapter the obtained results for temperature diode, ISFET and CV/O2-FET sensors will be presented. 3.2.1 Temperature Diode Diodes have current-voltage curve with a temperature dependency. The higher the temperature is the higher is the current flows though it. This will be also confirmed by the results in this chapter. 3.2.1.1 cMOS chips

Diode curve at 23°, 27° and 37°C of chip u01. Graph 3-5

For chip u01, at a current of 60 µA the voltage change is about −1.5 /° in a range of 23 to 37°C. It has been also observed how the temperature dependency on voltage reverses at 20.5mA and 1.26V. Therefore, above this point higher temperatures cause higher voltage.



To make measurements using the voltage to current circuit described in chapter 2.5.1.4 the applied must be 600mV. 3.2.1.2 nMOS chips The first attempts to detect a current with the nMOS chips were unsuccessfully, although the exact software and hardware setting work perfectly with the cMOS chips. We thought that there is a bonding failure. The received signal was near zero and had no characteristics of a known diode curve. While trying some different settings to determine the optimal current for an operation point of the cMOS chips, an idea came from observing some results of signals near zero: The current measuring unit Voltalab has a variable accuracy, which is dependent on the range and the number of samples in each measurement sequence. The expected and target current was 60µA. Therefore, the chosen range was from 10µA to 100µA. This range was for cMOS chips enough, but not for the nMOS chips. They have relative low diode current, and need a smaller range and more accuracy. The diode current begins to rise at 250mV compared to 500mV for cMOS chips.

Diode curve at 27°, 37° and 50°C of chip f8. Graph 3-6



For chip f8 at a current of 1 µA, the voltage change is approximately -100mV/°C in a range of 27 to 37°C. The linearity of the curve increases with higher currents, that’s because the convergence of logarithmic voltage near zero has a bigger radius than voltages with higher values, where it’s nearby the limit of the voltage as the current approaches infinity. Therefore, the error of linear approximation of the temperature diode curve rises rapidly below threshold voltage, where the slope of the curve begins noticeable to upsurge.

Diode curve at 27° and 37°C of chip f5. Graph 3-7

Moreover, the chip f5 at a current of 200 nA has also a voltage change of about −100 per degree Celsius in the same range of 27 to 37°C.



3.2.2 Reference MOSFET (nMOS) Determining the operating range and to prove the functionality of the sensor chip. Therefore, a socket with contacts to the reference transistor was needed. The pin box has no contacts to the reference transistor.

The curve of i5-ISFET-Ref. Graph 3-8

The resulted characteristic curve of the ISFET sensor in the range from 0V to 5V looks similar to a resistor characteristic curve. This is because the transistor is still in triode mode or linear region and didn’t reach the saturation region which needs voltages higher than 5V.



3.2.3 ISFET Sensor 3.2.3.1 cMOS chips

Characteristic curve of ISFET sensor on chip u01 sensor A. Graph 3-9

The influence the pH value on the characteristic curve is noticeable. A solution with a higher pH value, due the higher OH-ions concentration (electrical potential) on the gate surface, will cause to flow a higher current though the transistor n-channel. In other words; the higher is the pH value, the lower is the source drain voltage at a fixed channel current. This voltage change is about -40mV per pH change at a working point current of 300µA.

Measuring UDS(pH) with ISFET sensor on chip u01 sensor A @300µA. Graph 3-10



To make pH values measurement respect to time, calibrating measurements using two solutions with known pH values is needed. The index Uds can be easily changed to the corresponding pH value.

Measuring pH value respect to time. Graph 3-11

For more accuracy by long time measurements, in case that the pH value does not remain constant, a drift to time factor can be added. For the previous graphs a drift factor of -0.5mV/min or corresponding -0.0125pH/min can be used. 3.2.3.2 nMOS chips

Influence the pH value on the characteristic curve of i5-ISFET-A (at VE=2V). Graph 3-12



The influence the pH value on the characteristic curve here is also noticeable. A solution with a higher pH value has a higher transistor current.

Characteristic curve of ISFET on chip u01 sensor A(in weak inversion mode). Graph 3-13

In weak inversion mode, the resulted characteristic curve of the ISFET transistor looks similar to a characteristic curve of a real transistor regular working mode. The ISFET sensors exclusively on the nMOS chips have in this region a pH to current sensitivity. The current in this mode (in nA) is very low compared with the current flowing in the linear mode (in mA) within the same voltage range.

Measuring with ISFET sensor on chip f5 sensor A @20nA(in cut off region). Graph 3-14



So we get in weak inversions mode at a working point of -20nA a voltage to pH value sensitivity of = 3V/pH. Although noise at this low current was expected to be high, the measured signal as seen in the graph above is clear and constant at different pH values. The shielding of the measurement unit is much important, when measuring very low currents. Shielding the measurement unit does not mean only to keep the pin-box with the sensor chip in a faraday cage, but also to shield the cables and connectors using BNC cables and connectors and avoiding using extensions, where the contact resistance can accrue.



3.2.4 O2-FET Sensor 3.2.4.1 cMOS chips

-161,8-161,7-161,6-161,5-161,4-161,3-161,2-161,1-161,0

-159,8

-159,7

-159,6

-159,5

-159,4

-159,3

-50

0 10 20 30 40 50 60-600

0

NM

EN

ME

∆pH(cal)

I DS [m

A]

∆pH

∆pH

∆pH∆pH(DO)

∆pH(DO)∆pH(DO)

∆pH(DO)

∆pH(DO)without DO

pH8pH8

pH6pH6 pH6

U [m

V]

time [min]

I [n

A]

Measuring pH and DO with O2-FET on chip [email protected](smoothed by 50points). Graph 3-15

The pH change is around -1mA/pH. This can be calculated using the equation of “pH measurement without reduced hydroxide. Equation 2-24”. Where the calibration solution is one with pH value of 8, and target solution to measure has pH of 6. ∆ = −161.3 + 159.3 = −2 = −2 2pH = −1 / The DO pH change at a pH value of 8 can be calculated using the equation of “Calculating pH change due oxygen reduce. Equation 2-25”:

∆pH(DO) =0µA

∆pH(DO) =350µA

Characterization of miscellaneous multi

∆ ( ) =∆ ( ) = So we get ∆ ( ) = 450 3.2.4.2 nMOS chips

Measuring pH and DO with O

The surface area of the NME is 2.5 times bigger than the Clark sensor on the same chip. The measured INMEcurrent measured in chapter 3.1.1.2 The pH change is around +35µ“pH measurement without reducedcalibration solution has a pH valuof 6.


multi parametrical silicon based biosensor chips

) = −161.25 + 161.7 = 450µ = −161.6 + 161.7 = 100µ

450µ − 100µ = 350µ

Measuring pH and DO with O2-FET on chip [email protected]. Graph 3-16

The surface area of the NME is 2.5 times bigger than the Clark sensor on the NME therefore is also 2.5 times bigger than the

3.1.1.2.

+35µA/pH. This can be calculated using the equation of without reduced hydroxide. Equation 2-24”. Where the

pH value of 8, and target measuring solution has

∆pH(DO) =-22µA

∆pH(DO) =0µA


- 91 -

The surface area of the NME is 2.5 times bigger than the Clark sensor on the the Clark

A/pH. This can be calculated using the equation of ”. Where the

solution has a pH



∆ = −285µ + 325µ = 40µ = 40µ 2pH = 20µ / The DO pH change at a pH value of 8 can be calculated using the equation of “Calculating pH change due oxygen reduce. Equation 2-25”: ∆ ( ) = −285µ + 260µ = −25µ ∆ ( ) = −295µ + 292µ = −3µ So we get ∆ ( ) = −25µ + 3µ = −22µ E.g. a ∆ ( ) of -11µA means the oxygen concentration is 50%. That was simply calculated using the equation for calculating Percentage of DO content in a measuring electrolyte. Equation 2-26 [ ] = −11µ −22µ = 50%



3.2.5 CV-FET Sensor (nMOS) For characterization three types of measurements were made. The first one was the pH value measurement of a usual PBS solution. The second was the measurement of dissolved oxygen. For that a PBS solution with air saturated oxygen and another one with bonded oxygen is used. The third one was done to measure the concentration of dissolved KMnO4 within different concentrated solution. All measurements are done using a working point UDS of 2.5V. MEASURING PH VALUE:

Voltammetry curves for pH PBS solutions (chip c10). Graph 3-17

For the first measurement electrolytes with air saturated oxygen were used. The pH values are pH6, pH7 and pH8. From the characterization of ISFET sensors we know that the measured pH values were linear. This means that the current between pH6 and pH7 has the same current as the difference between pH7 and pH8.

Ic[pH] ~-75µA

IL~-150nA

ΔI0=-60µA



In the last graph the current of the solution with pH8 at a UNME voltage of 0V has a higher value than usual. The expected current is around 50µA lower than the incorrect measured value. So we add a correction current ΔI0 of -60µA. The biggest current for one pH value change is around -70µA. An easier way to find this value is to normalize the current of pH so the current curve pH set as zero level. The new normalized current [ ] can be written for a substance x in general as: [ ] = ( [ ]) − ( [ ]) + ∆

Normalized concentration current. Equation 3-2

Where: ( [ ]) is the source-drain current of an electrolyte with the

base (zero level) concentration of a dissolved substance x, ( [ ]) is for the next electrolyte with a different concentration, ∆ is the correction current.

For the measurement example used here the last equation can be written as: = ( 6)− ( 7)− 60µ for normalizing curve of pH7 = ( 6)− ( 8)− 60µ for normalizing curve of pH8

-1,0 -0,5 0,0 0,5 1,00

-25

-50

-75

-100

-125

-150

-175

Normalized pH concentration current to pH 7 (chip c10). Graph 3-18

UNME[V]

IpH [µA]

pH 8

pH 7

Ic[pH] ~-75µA



MEASURING CONCENTRATION OF DISSOLVED OXYGEN:

Voltammetry curves for oxygen dissolved PBS solutions (chip c10). Graph 3-19

The solution with added Na2SO3 has a pH value a little higher than pH8. The results from the last measurement shows, that the current is linear with the pH value of the electrolyte. Anyway the curve of Na2SO3 has a very constant current even in different pH concentration. Correction factor is –as can be seen from the last graph- about 40µA [ ] = ( [0%]) − ( [100%]) − 40µ for normalizing curve of 100% DO

IL~-120nA

IL~-0nA

Ic[DO] ~-370µA

ΔI0=40µA



-1,0 -0,5 0,0 0,5 1,0

-350

-300

-250

-200

-150

-100

-50

0

50

100

150

Normalized DO concentration current (chip c10). Graph 3-20

The normalized curve of the air saturated oxygen has a maximum current of around -370µA. As long the concentration and current are linear dependent, the percentage [ ] of an unknown concentration can be calculated using the fallowing formula: [ ] = [ ] [ ] ∙%

Calculating the percentage of an unknown concentration. Equation 3-3

Where: [ ] is the normalized current of the electrolyte with the unknown

concentration of the substance x, [ ] is the normalized current of the calibration electrolyte. Calibration is done usually with a 100% electrolyte, % is the percentage of the concentration of the known calibration electrolyte.

E.g. a current of -200µA and a current of -370µA for a 100% concentration has a concentration of 54%. [ ] = ∙ = 54%

UNME[V]

Ic[DO] [µA]

100% DO

Ic[DO] ~-370µA



MEASURING CONCENTRATION OF DISSOLVED SODIUM SULFITE:

Voltammetry curves for MnO4- dissolved PBS solutions (chip c10). Graph 3-21

Three concentrations are used: At 1mM, 0.5mM and 0mM KMnO4 as calibration electrolyte for the normalization. The used base electrolyte is PBS solution, with dissolved oxygen. The normalized curve of 1mM KMnO4 has a maximum current of around 225µA. The concentration and current are not direct proportional to each other. So the formula used for calculating the percentage of an unknown concentration can not be used here. This is because 0.5mM has in normalized form a current of 75µA. This is about one third of the current, which the 1mM dissolved KMnO4 has.

ΔI0=-15µA

IL~-70nA

IL~-160nA

Ic[MnO4-] =150µA =75µA



-1,0 -0,5 0,0 0,5 1,0

-50

-25

0

25

50

75

100

125

150

175

200

225

Normalized KMnO4 concentration current (chip c10). Graph 3-22

The correction factor is small. It is only -15µA. So the new curves are: [ ] = ( [0 ]) − ( [1 ]) − 15µ for 1mM KMnO4 and [ ] = ( [0 ]) − ( [0.5 ]) − 15µ for 0.5mM KMnO4 In the UNME range of -0.4V to -0.9V; the solution with a KMnO4 concentration of 0.5mM has a normalized constant current of 75µA, and the other one with the concentration of 1mM has a normalized current of 225µA.

Ic[MnO4] [µA]

UNME[V]

1.0mM

0.5mM

Ic[MnO4-] =150µA =75µA

Problems and Solutions


4 Problems and Solutions In this chapter, the main problems while doing the measurements will be explained. Several suggestions to solve and avoid them are also given.

4.1 Contacting errors

Contact error of i5-ISFET-Ref. (at UE=2V). Graph 4-1

SOME ERROR PATTERNS:

- Relatively small current although high voltage. - Unexpected plot run e.g. symmetries or jumps. - Misinterpretation of measurement data:

Jumps can be caused by an error from measuring device e.g. by accuracy change of the measurement unit or by electrostatic discharges on reversion of polarity.



4.2 Loosing of the passivation layer SIGNS OF A BAD PASSIVATION LAYER:

- A main sign for bad passivation layer is seeing bubbles from water electrolysis coming out from the chip surface, or rather, from areas, where the metal contacts under the passivation layer run.

- When measuring sometimes we get an unexpected response signal

from the ISFET, although there is no reference electrode connected. A logical explanation for it is that an open passivation layer causes the metal wires beneath it to have a contact to the electrolyte. This unwanted contact works like a reference electrode. This can be confirmed by measuring current flowing between the suspected contact and a free reference electrode in electrolyte.

- Too high currents of the electrodes on the chip like the Clark work

electrode and the NME around the ISFETs.

ISFET after a long term measurement [STEP06]. Picture 4-1



“While measuring it builds air bubbles on the media above the metal conductor lines, which causes to an electrical breakdown through the passivation (electrolysis of water). After a long time measurement the passivation layer above the metal lines are loosening completely.”[STEP06] Using polarization filter under microscope unremarkable scratches can be made visible. The loosing of the passivation layer begins with these scratches. So it’s strongly recommended to select sensors without any scratches when the aim is to make long term measurements.

Scratches on the passivation layer. Picture 4-2

The passivation layer is a non-conducting oxide isolator. However, under voltage can accrue electrical breakdowns, which make the layer loose more and more.

Loosed passivation layer. Picture 4-3



To prevent this, it is highly recommended to avoid using additional voltage like the extra voltage UE. It can be useful to use a negative -UE. This negative –UE voltage reduces UPM voltage. Therefore, this will reduce the possibility of electrical breakdowns.

Potential divider circuit. Picture 4-4

Potential divider. Equation. 4-1

RP is the resistance of the passivation layer and RE of the electrolyte. The change of URS -according to the law of the potential divider- effects UPM more than URP. That is because RP is higher than RE.

U1PM = URS + -URP without UE U2PM = URS - URP + UE with +UE

U3PM = URS - URP - UE with -UE

U3PM < U1PM < U2PM

Passivation-metal conductor voltage. Equation. 4-2



4.3 Noise

An example for a filtered and unfiltered signal. Graph 4-2

Some recommends to reduce noise:

- Setting the measuring device to a constant accuracy. - Using a filter to remove high frequency noise. Experience value is 100ms. - If periodic oscillations accrue, then it can be because of a bubble on the sensor. - Using Faraday cage with grounding. - Setting smaller sample rate when measuring. - As possible, measuring with high currents and voltages. - Measuring with the calculated open circuit potential drift points. - Shielding the cables and connectors - Using BNC cables and connectors - Avoid using extension adapters and cables, whereat the contact resistance can accrue.



4.4 Signal drops while measuring

Air bubbles falsify measurements. Graph 4-3

This is a sign of air bubbles on the sensor contact surface with the electrolyte fluid. Rinse the sensor surface area with distillated water and clean it with ethanol this can avoid air bubbles to build while filling the sensor with fluid.

4.5 Digital rounding errors When using units with digital displays, it is important to know the rounding error of it. To avoid this, the most of the measurement units have the option to show the measured value in different ranges. If there is no option to select the working range, attaching an extra measuring unit can be helpful. The power supply used to characterize the reference MOSFET had no option to select the display range. The voltmeter is used to control the adjusted voltage. When the display of a power supply does not have enough digits to display the applied voltage exactly, a rounding error up to 10% can falsify the displayed value.



The used Power supply and a voltmeter [CONR08]. Picture 4-5 The used voltage source Voltcraft VCL1303pro. It has only one digit after the radix point. Because the missing second and third digit after the radix point, which can be 99, a voltage of 1.099V can be shown inaccurate on the units display as “01.0V”. In the

4.6 Unclean sensor surface

- Fluids remaining from the last measurement may change the electrochemical behavior of the next measurement and that will falsify the results.

- Sensor surface must always be rinsed with distilled water. The dried substances can be dissolved in the new added fluid.

- A sign for residue from the last fluid is that the measured values are much near to each other than they usually are.

Conclusions and outlook


5 Conclusions and outlook The main results can be summarized in the table below:

cMOS nMOS Sensitivity Working point Sensitivity Working point

TD -1.5mV/°C 60µA -100mV/°C 1µA Clark -11nA -500mV -7nA -500mV IDES -40Ω/75mM 30mV@10kHz -6Ω/75mM 30mV@10kHz pH-ISFET -40mV/pH 300µA 3V/pH 22nA O2-FET 350µA/∆O2 -1.5V, pH8 -22µA/∆O2 -1.5V, pH8

The main characterization results of the cMOS and nMOS chips. Table 5-1

Some remarkable results from the table above are:

- Temperature diode on nMOS chip has a very high temperature dependency. This dependency is much higher than the dependency of a usual diode. The measurements are repeated several times and this high dependency is confirmed.

- Measuring results of the Clark sensor on both of the chip are in the same range.

- IDES sensor measurements are contact area dependent. The bigger the contact surface is, the higher is the conductivity.

- ISFET sensors in nMOS chips have in triadic operating mode much less pH dependency as cMOS in the same operating mode.

- Also in the weak inversion mode, the ISFET sensors on the nMOS chips can measure pH value, with a high sensitivity of up to 3V/pH. The cMOS chips cannot measure pH in this mode.

- The ISFET sensors in nMOS have positive pH sensitivity, while the cMOS a negative one.

- Measuring dissolved oxygen on cMOS chips was more successfully and with a higher sensitivity.



CV-operating mode still experimental and needs more tests. Anyway the results achieved were showed clearly that this measuring method works. AGING:

Before beginning with this assay, all the chips were optically searched under microscope for errors and they were all OK.

cMOS u01 u02 u03 TD OK OK OK Clark OK OK OK IDES OK OK OK ISFET A OK OK OK ISFET B OK OK OK ISFET C OK OK OK ISFET D OK OK OK O2-FET 1 X X OK

Error developing of the cMOS chips. Table 5-2

The ISFETs sensors of cMOS chips are still working and there is no visual errors found under microscope. The CV/O2-FETs lose parts from its metallic electrode ring. The protecting passivation layer is still intact.

nMOS c6 c10 i4 i5 i6 f5 f8 TD OK OK OK OK OK OK OK Clark OK OK OK OK OK OK X IDES OK OK OK X X X OK ISFET A X X OK X X OK* OK ISFET B X X X X X OK* OK ISFET C OK OK OK X X OK* OK ISFET D X OK OK X X OK* OK O2-FET 1 OK X X X X X X O2-FET 2 OK OK* OK OK* OK OK OK

Error developing of the nMOS chips. Table 5-3



- The main damage on the chips is the passivation layer. As next comes

the nobel metal electrode. It loses with time. - Only operated sensors were aging and building damages. Not used

sensors have no errors; although they had always contact with fluid as the operated sensors.

- The each sensor was operated on average time of 10 hours, and that is at least by using 3 different electrolytes.

- Temperature sensors have no contact with the electrolyte fluid; therefore it has no aging problem.

OUTLOOK: At this point monitoring changes was only possible qualitatively. To gain quantitative information the details of the processes have to be investigated and more test runs with statistical evaluations have to be done. Necessary further investigations should be dedicated to: - Electrode aging. - Influence of temperature and light. - Measuring using PBS or distilled water without dissolved oxygen. - Detailed investigation of voltammetry curves of various substances. - Sensor ageing (drift, change of electro catalytic activity, lifetime). - Operating more than one sensor for simultaneous measurements. To achieve absolute measurements by FET-Sensors especially the ageing and the variation of the operating point/range due to production processes have to be investigated. No long term measurements have been tried during this work. The maximal measurement time was about three hours. The sensors have been examined individually. The O2 concentration in the medium can be reduced by injection of N2 gas into the solution. When the solution is in thermodynamic equilibrium with the nitrogen atmosphere, the oxygen content will be zero. The return to the original O2 concentration by diffusion from the surrounding air after 10 min of N2 injection takes hours. This method is for sure better than adding oxidation substance to bond the dissolved oxygen. Any additional substances can have complicated influence on the electrochemical characteristics of the fluid.

Acknowledgments


6 Acknowledgments Firstly I would like to express my sincere appreciation to all those who have contributed, directly or indirectly, to this diploma thesis in form of technical or other support. I want to thank Mr Prof. Dr. B. Wolf for the opportunity to develop this interesting diploma thesis at his chair, my mentor Mr Dipl.-Ing. Joachim Wiest for his expert guidance and professional advises, Mr Dr. M. Brischwein for helping by the measurements in the bio laboratory, Mr Dr. J. Peter for his support in chemical problems, Mr R. Arbogast and Mr W. Ruppert for their help in the shop work, Mr A. Michelfelder and Ms G. Teschner for the assistance by working with fluids, Mr F. Ilchmann for his support with computer equipments, Ms M. Remm for helping using the microscopes, and I would like also to thank all other people at the Lehrstuhl für Medizinische Elektronik who were very helpful in providing information. A special thank goes to my family and my friends for their unlimited support while my study at the technical university of Munich

Indexes


7 Indexes 7.1 Index of pictures Electrochemical cell. Picture 1-1 ...................................................................................................................................... 4 The used microscopes with digital cameras. Picture 2-1 ........................................................................................ 7 Wiring schema for the production of Ag/AgCl electrode. Picture 2-2 ............................................................ 14 The used incubator. Picture 2-3 ..................................................................................................................................... 17 The used Power supply [CONR08]. Picture 2-4 ........................................................................................................ 19 Measurement unit PGZ402 [RADI68]. Picture 2-5 .................................................................................................. 21 GUI interface of the VoltaMaster 4. Picture 2-6 ....................................................................................................... 22 Available settings for Open Circuit Potential measuring method. Picture 2-7 ............................................ 23 Available settings for Pot. Cyclic Voltammetry measuring method. Picture 2-8 ........................................ 24 Available settings for Chrono Potentiometry measuring method. Picture 2-9............................................ 24 Available settings for Chrono Ameperometry measuring method. Picture 2-10 ........................................ 25 Available settings for Pot. Fixed Freq. EIS (Capacitance) measuring method. Picture 2-11 ................. 25 The cMOS chip and its sensors. Picture 2-12 ............................................................................................................. 27 Pins assignment (not true to size). Picture 2-13 ...................................................................................................... 28 The nMOS chip and its sensors. Picture 2-14 ............................................................................................................ 30 The sensor chips on the nMOS 4 inch wafer. Picture 2-15 ................................................................................... 31 Pins assignment (not true to size)[WIES05]. Picture 2-16 .................................................................................. 32 Picture of the used pin box. Picture 2-17 .................................................................................................................... 34 Cause of diffuse current of dissolved oxygen [ISRA07]. Picture 2-18 .............................................................. 39 Clark sensor on the cMOS chip. Picture 2-19 ............................................................................................................. 42 Clark sensor on the nMOS chip. Picture 2-20 ............................................................................................................ 42 Schematic design of the measuring system. Picture 2-21 .................................................................................... 43 Measurement assembly. Picture 2-22 .......................................................................................................................... 43 An ideal circuit for measuring an impedance Z. Picture 2-23 ............................................................................ 46 Realistic circuit incl. interfering components. Picture 2-24 ................................................................................ 47 Four-wire impedance measurement circuit. Picture 2-25 ................................................................................... 47 IDES sensor on the nMOS chip. Picture 2-26 ............................................................................................................. 48 IDES sensor on the cMOS chip. Picture 2-27 .............................................................................................................. 49 Schematic design of the measuring system. Picture 2-28 .................................................................................... 49 Temperature diode on the cMOS chip. Picture 2-29............................................................................................... 54 Temperature diode on the nMOS chip. Picture 2-30 .............................................................................................. 55 Schematic design of the measuring system. Picture 2-31 .................................................................................... 55 MISFET [HENN05]. Picture 2-32 ................................................................................................................................... 57 Source-drain current. Graph 2-10, Picture 2-33 ...................................................................................................... 58 Reference MISFET on the nMOS chip. Picture 2-34 ................................................................................................ 60 Schematic design of the measuring system. Picture 2-35 .................................................................................... 61 Effect of the hydroxide on the source drain current. Graph 2-11, Picture 2-36 .......................................... 62 ISFET sensor 4 on the cMOS chip. Picture 2-37 ........................................................................................................ 64 ISFET sensor on the nMOS chip. Picture 2-38 ........................................................................................................... 64 Measurement assembly of the project. Picture 2-39 .............................................................................................. 65 Schematic design of the measuring system. Picture 2-40 .................................................................................... 65

Indexes


Effect of the hydroxide on the source drain current. Graph 2-12, Picture 2-41 .......................................... 67 ISFET sensor on the cMOS chip. Picture 2-42 ........................................................................................................... 71 ISFET sensor on the nMOS chip. Picture 2-43 ........................................................................................................... 71 Schematic design of the measuring system. Picture 2-44 .................................................................................... 72 Effect of the hydroxide on the source drain current. Graph 2-14, Picture 2-45 .......................................... 74 Roughness factor and the length. Picture 3-1........................................................................................................... 78 ISFET after a long term measurement [STEP06]. Picture 4-1 ......................................................................... 100 Scratches on the passivation layer. Picture 4-2 ..................................................................................................... 101 Loosed passivation layer. Picture 4-3 ........................................................................................................................ 101 Potential divider circuit. Picture 4-4 .......................................................................................................................... 102 The used Power supply and a voltmeter [CONR08]. Picture 4-5 ..................................................................... 105 7.2 Index of graphs The measured electrolysis voltage at 4mA for producing Ag/AgCl. Graph 2-1 ........................................... 15 Electrolysis current for producing Ag/AgCl. Graph 2-2 ........................................................................................ 16 Damped oscillations of the incubator. Graph 2-3 .................................................................................................... 18 Measurement of a 10MΩ resistor with the PGZ402 unit. Graph 2-4 ............................................................... 23 Typical voltammogram of Clark sensor. Graph 2-5 ............................................................................................... 38 An example for a voltammogram voltage. Graph 2-6 ........................................................................................... 44 AC signal for impedance acquisition. Graph 2-7 ...................................................................................................... 50 Influence of frequency on impedance[BRIS06]. Graph 2-8 .................................................................................. 50 I-V characteristic curve of a diode and the influence of temperature. Graph 2-9 ...................................... 53 Source-drain current. Graph 2-10, Picture 2-33 ...................................................................................................... 58 Effect of the hydroxide on the source drain current. Graph 2-11, Picture 2-36 .......................................... 62 Effect of the hydroxide on the source drain current. Graph 2-12, Picture 2-41 .......................................... 67 Run of the curves of the PBS with and without dissolved oxygen. Graph 2-13 ............................................ 69 Effect of the hydroxide on the source drain current. Graph 2-14, Picture 2-45 .......................................... 74 Voltammogram curve of the clark sensor on chip u01. Graph 3-1 ................................................................... 78 Voltammogram curve of the clark sensor on chip f5. Graph 3-2....................................................................... 79 Measuring with IDES sensor on chip u01. Graph 3-3 ............................................................................................ 80 Measuring with IDES sensor on chip f8. Graph 3-4 ................................................................................................ 80 Diode curve at 23°, 27° and 37°C of chip u01. Graph 3-5..................................................................................... 82 Diode curve at 27°, 37° and 50°C of chip f8. Graph 3-6 ........................................................................................ 83 Diode curve at 27° and 37°C of chip f5. Graph 3-7 ................................................................................................. 84 The curve of i5-ISFET-Ref. Graph 3-8 ........................................................................................................................... 85 Characteristic curve of ISFET sensor on chip u01 sensor A. Graph 3-9 .......................................................... 86 Measuring UDS(pH) with ISFET sensor on chip u01 sensor A @300µA. Graph 3-10 ................................. 86 Measuring pH value respect to time. Graph 3-11 .................................................................................................... 87 Influence the pH value on the characteristic curve of i5-ISFET-A (at VE=2V). Graph 3-12 .................... 87 Characteristic curve of ISFET on chip u01 sensor A(in weak inversion mode). Graph 3-13 .................. 88 Measuring with ISFET sensor on chip f5 sensor A @20nA(in cut off region). Graph 3-14 ..................... 88 Measuring pH and DO with O2-FET on chip [email protected](smoothed by 50points). Graph 3-15 ............. 90 Measuring pH and DO with O2-FET on chip [email protected]. Graph 3-16 .............................................................. 91 Voltammetry curves for pH PBS solutions (chip c10). Graph 3-17 ................................................................... 93 Normalized concentration current of DO in PBS solutions (chip c10). Graph 3-18 .................................. 94 Voltammetry curves for oxygen dissolved PBS solutions (chip c10). Graph 3-19 ...................................... 95 Normalized concentration current of DO in PBS solutions (chip c10). Graph 3-20 .................................. 96 Voltammetry curves for MnO4- dissolved PBS solutions (chip c10). Graph 3-21 ......................................... 97 Normalized concentration current of DO in PBS solutions (chip c10). Graph 3-22 .................................. 98 Contact error of i5-ISFET-Ref. (at UE=2V). Graph 4-1 ........................................................................................... 99 An example for a filtered and unfiltered signal. Graph 4-2 ............................................................................... 103

Indexes


Air bubbles falsify measurements. Graph 4-3 ......................................................................................................... 104

7.3 Index of equations Molarity Equation. Equation 2-1 ................................................................................................................................... 11 Reference electrode current. Equation 2-2 ................................................................................................................ 13 The voltage of reference electrode. Equation 2-3 ................................................................................................... 13 Half reaction the Ag side. Equation 2-4 ...................................................................................................................... 14 Half reaction the Pt side. Equation 2-5 ....................................................................................................................... 14 The whole chemical reaction for producing Ag/AgCl electrode. Equation 2-6 ........................................... 15 Diffusion flux. Equation 2-7 ............................................................................................................................................. 40 Diffusions current. Equation 2-8 .................................................................................................................................... 40 Diffusion Current respect to time t. Equation 2-9 ................................................................................................... 40 Oxygen concentration current. Equation 2-10 ......................................................................................................... 40 Chemical reaction to bind dissolved oxygen. Equation 2-11 .............................................................................. 42 Diffusions current. Equation 2-12 ................................................................................................................................. 44 Complex Ohm’s law. Equation 2-13 .............................................................................................................................. 46 Real and complex component of impedance. Equation 2-14 .............................................................................. 51 Schockley’s diode law. Equation 2-15 .......................................................................................................................... 52 Schockley’s simplified diode law. Equation 2-16 ..................................................................................................... 52 Diode law in respect to voltage. Equation 2-17 ....................................................................................................... 53 Thermal voltage. Equation 2-18 .................................................................................................................................... 53 pH value dependency on the concentration of −. Equation 2-19 ............................................................. 62 pH measuring sensitivity in voltage per pH . Equation 2-20 .............................................................................. 66 Reduction of dissolved oxygen. Equation 2-21 ......................................................................................................... 67 pH change depending on oxygen reduction. Equation 2-22 ............................................................................... 68 Hydroxide and hydronium ions from water. Equation 2-23 ............................................................................... 68 pH measurement without reduced hydroxide. Equation 2-24 ........................................................................... 68 Calculating pH change due oxygen reduce. Equation 2-25 ................................................................................. 69 Percentage of DO content in a measuring electrolyte. Equation 2-26 ............................................................ 73 Dissociation of water. Equation 2-27 ........................................................................................................................... 74 Reducing of dissolved XO. Equation 2-28 ................................................................................................................... 74 Reducing of dissolved MnO4-in PBS. Equation 2-29 ................................................................................................ 75 Extended oxygen concentration current. Equation 3-1 ........................................................................................ 77 Potential divider. Equation. 4-1 ................................................................................................................................... 102 Passivation-metal conductor voltage. Equation. 4-2 ........................................................................................... 102 7.4 Index of tables Used sensors on silicon and thin film technologies. Table 1-1 .............................................................................. 5 PBS buffer composition. Table 2-1 ................................................................................................................................ 11 Used sodium sulfite concentration for bonding dissolved oxygen. Table 2-2 ............................................... 11 Concentration of the NaCl to double the amount of the free ions. Table 2-3 ............................................... 12 Specifications cable of the PGZ402. Table 2-4 .......................................................................................................... 22 Fast compare between cMOS and nMOS chips. Table 2-5 .................................................................................... 26 Pins assignment of the pin box. Table 2-6 .................................................................................................................. 30

Indexes


Pins assignment of the cMOS chips. Table 2-7 .......................................................................................................... 33 Pins assignment of the nMOS chips. Table 2-8 ......................................................................................................... 37 Pins assignment of the Clark sensor. Table 2-9 ........................................................................................................ 41 Pins assignment of the IDES sensor. Table 2-10 ...................................................................................................... 48 Pins assignment of the temperature diode. Table 2-11 ........................................................................................ 54 Pins assignment of the cMOS chips. Table 2-12 ....................................................................................................... 59 Pins assignment of the cMOS chips. Table 2-13 ....................................................................................................... 60 Pins assignment of the ISFET sensors. Table 2-14 .................................................................................................. 63 Pins assignment of the O2-FET sensor. Table 2-15 .................................................................................................. 70 Compare between O2-FET sensors of the cMOS and nMOS chips. Table 2-16 .............................................. 71 The main characterization results of the cMOS and nMOS chips. Table 5-1 .............................................. 106 Error developing of the cMOS chips. Table 5-2 ...................................................................................................... 107 Error developing of the nMOS chips. Table 5-3 ...................................................................................................... 107 Explanation of the used abbreviations and symbols. Table 8-1 ...................................................................... 118 Bibliographies. Table 9-1 ................................................................................................................................................ 122

List of abbreviations and symbols


8 List of abbreviations and symbols Abbreviation Definition

Ampere meter

Voltmeter

DC voltage Source

AC voltage source

AC current source

Adjustable voltage source

Impedance, complex Resistor

Resistor

Operation amplifier

, Grounding

, Contact port, probe

∂ Derivative

® Registered trade mark

°C Degree Celsius



A Ampere

A Area

Ag Silver

Aux Auxiliary port

BNC connector Bayonet Neill-Concelman connector

C Coulomb

c[x] Concentration of the substance x

Cl Chlorine

cMOS Complementary Metal Oxide Semiconductor

cO2 Oxygen concentration

CV Cyclovoltammetry

CV-FET Cyclovoltammetry-FET

D Diffusions constant

D Drain

d diameter

Dipl.-Ing. Diplom Ingenieur

DO Dissolved oxygen

Dr Doctor

E Electrolyte

Ex Energy of x F Faraday constant 96485 C/mol

FET Field effect transistor

G Gate

GUI Graphical User Interface



I Current

i.e. id est, that is

IDES Interdigitated Electrode Structures

IEEE Institute of Electrical and Electronics Engineers, Inc.

IHP Inner Helmholtz Plane

iL Limit current

IMOLA Intelligent Mobile Lab

IS Saturation current of a diode

ISFET Ion Sensitive Field Effect Transistor

Jx Flux of x

K Kelvin

k, kB Boltzmann’s constant 8.617 × 10−5 eV/K

KMnO4 Potassium permanganate

l Liter

LME Lehrstuhl für medizinische Elekronik, Chair for medical electronics

M Metal contacts from e.g. Drain or Source

M, mol Mole

MOSFET Metal–Oxide–Semiconductor Field-Effect Transistor

Mr Mister

Ms Mistress

n Number of free transported electrons

N Nitrogen

n/a not applicable



Na Sodium

Na2SO3 Sodium Sulfite

Na2SO4 Sodium Sulfate

nMOS n-Chanel Metal oxide Semiconductor

O Oxygen

O2-FET Oxygen FET

OHP Outer Helmholtz Plane

P Passivation (Oxide protection layer)

PBS solution Phosphate-Buffered Saline solution

PC Personal computer

PLCC Plastic Lead Chip Carrier

Prof Professor

q Elementary charge 1.602 × 10-19 C

q.v. quod vide, see also

R Reference electrode

R Resistor

r Radius

R Gas law constant 8.314 J/(K mol) REF Reference

S Source

SNR Signal to Noise Ratio

T Temperature in Kelvin

t Time

TD Temperature diode



TUM Munich University of Technology

U Voltage

U-I, V-I Voltage-current

UIx Voltage of the current Ix, so that =

UT Thermal voltage

Uxy Voltage between x and y.

V Volt

viz Videlicet, precisely

WK Work port

x At position x

x#-ISFET-Y ISFET number Y on the sensor chip number x#

α Dependent, proportional

Explanation of the used abbreviations and symbols. Table 8-1

Bibliography


9 Bibliography

Abbr. Autor(s)

Title of literature Publisher, Year

[BAHR02]

L. Bahr Evaluirung planarer Sensorstrukturen zur Messung der

zellulären Respiration LME, TUM, 2002

[BARD00] A. Bard and L. Faulkner

Electrochemical Methods: Fundamentals and Applications John Wiley & Sons, 2nd Edition, 2000

[BRIS06] M. Brischwein

Script Praktikum Bioelektronische Messtechnik WS06/07 LME, TUM, 2006

[CONR08]

Conrad, Lin. Labornetzgerät VLP-1303 Pro, No.: 511401 http://www.conrad.de/Elektronik-

Messtechnik/lin_labornetzgerat_vlp-40.sap Conrad, 10.04.2008

[EMIN07] Y. Eminaga

Evaluierung Silizium basierter biohybrider Mikrosensoren LME, TUM, 2007

[EMIN072] Y. Eminaga

Praktikum Bioelektronische Messtechnik

http://www.conrad.de/Elektronik

Bibliography


LME, TUM, 2007

[EMIN08] Y. Eminaga

Evaluation of nMOS manufactured ISFETs LME, TUM, 2007

[HENN05]

M. Hennig 2005 GNU-licence, MIME-Typ: image/png

http://upload.wikimedia.org/wikipedia/de/7/7b/N-Kanal-MOSFET.png 21.04.2008

[HEYW88] W. Heywang

Sensorik, Band 17 der Reihe HalbleiterElektronik Springers Verlag, 3rd edition, 1988

[HITC78] L. Hitchman

Chemical Analysis Vol. 49, Measurement of dissolved Oxygen John Wiley & Sons, New York, 1978

[ISRA07]

M. Israel BioChip-Impedanzspektroskopie / Entwicklung eines

Impedanzmessgerätes auf Basis des AD5933 LME, TUM, 2007

[MACA78] R.G. Bates and J.B. MacAskill

Standard Potential of the Silver-Silver Chloride Electrode Pure & Applied Chem., Vol. 50, 1978

[MICH06] A. Michelfelder

PBS Herstellung.doc LME, TUM, 13.09.2006

[MOHR00] P. J. Mohr and B. N. Taylor

CODATA recommended values of the fundamental physical constants: 1998

http://upload.wikimedia.org/wikipedia/de/7/7b/N-Kanal

Bibliography


Rev. Mod. Phys., Vol 72, No. 2, April 2000

[MSZE98] S. M. Sze

Modern Semiconductor Device Physics Wiley Interscience, 1998

[MUGG02]

H. Muggenthaler Amperometric oxygen sensors on silicon and glass chips for the determination of cellular respiration: Calibration and evaluation

LME. TUM, 2002

[NAGY08]

Z. Nagy and E. Yeager Electrochemistry Dictionary, Center for Electrochemical

Sciences, Case Western Reserve University, Cleveland Revision date: January 14, 2008

[RADI68] http://www.radiometer-

analytical.com/en_product_details_inc.asp?pid=68 01.05.2008

[STEP06] C. Stepper

Entwurf, Herstellung und Charakterisierung von Biosensorchips LME, TUM, 2006

[WIES03]

J. Wiest Measurement of pH and pO2 change at an ISFET surrounded by a

noble metal electrode LME, TUM, 2003

[WIES05] J. Wiest

Cellular Assays with Multiparametric Bioelectronic Sensor Chip CHIMIA 2005, 59, No. 5

[GÖBE06] H. Göbel

Einführung in die Halbleiter-Schaltungstechnik 2. Auflage, Springer Verlag, 2006

http://www.radiometer

Bibliography


[FARM98]

J. Farmer Waste Package Degradation Expert Elicitation Panel: Input on

the Corrosion of CRM Alloy C-22 Lawrence Livermore National Laboratory, 1998

[GEST08]

GESTIS-database on hazardous substances Sodium sulfite

http://biade.itrust.de/biaen/lpext.dll/Infobase/uberschrift39184/glied139185.htm#JD_id570201

German institutions for statutory accident insurance and prevention, 04.02.2008

Bibliographies. Table 9-1

http://biade.itrust.de/biaen/lpext.dll/Infobase/uberschrift3918

Appendix


10 Appendix This work also includes the followings: CD CONTENT: - Raw data of the measurements. - MS Excel data sheets. - Origin Files. - Cover page in MS Word and PDF formats. - MS Powerpoint presentation of this work. - Picture files of the figures used in this document. - This document in PDF and MS-Word 2007 docx format. - Demo and free version of some programs used in this work. PRINTED MEDIA:

- Cover page. - Three copies in color of this documentation.

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