Micro scale: ~µm-~mm Nano scale: ~nm-~µm …fangang/NEW_WEB_2002/L4/... · y BioMEMS drug...
Transcript of Micro scale: ~µm-~mm Nano scale: ~nm-~µm …fangang/NEW_WEB_2002/L4/... · y BioMEMS drug...
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NTHU ESS5845 Nano/micro Biomecidal and Fluidic System F. G. Tseng Spring/2004, lec 1, p1
Lecture 1 Introduction to Nano/micro Biomedical and Fluidic Systems
Scope of This Course: Introduction and study of the principles and applications of micro/nano sized biomedical/fluidic systems in current stage and potential possibilities in the future.
Goal: To help on your nano/micro biomedical/fluidic system design in choosing right principles and applications from the systematic study for the specific field of life science.
Definition of nano/micro biomedical/fluidic systems:
Micro scale: ~m-~mm
Nano scale: ~nm-~m
Devices/systems point of view:
Miniaturized systems, integrate sensing, control and actuation units on a chip, for bio-molecules or cell process applicable for the purposes of diagnosis, monitoring, drug screening, drug delivery, etc
Do we really need micro/nano biosystems?
>6 billion people on our planet needing all forms of molecular diagnosis including cancer screening, risk profiling and detection Potential pathogens drawn from
~1.5M species of fungi ~800,000 species of bacteria All possibly with drug resistance genes
Food, water, agricultural and environmental testing needs
=>Perhaps the need for >15 billion molecular tests per year!!!
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NTHU ESS5845 Nano/micro Biomecidal and Fluidic System F. G. Tseng Spring/2004, lec 1, p2
(Peter Gascoyne - UT MDACC)
Why Micro/nano fabricated? Advantages:
a. shorter process time b. scarce sample/assay amount (nl-pl) c. low cost d. automation e. high throughput Challenges:
a. multi-disciplinary b. integration c. weak signal d. relibility comparison between micro process and micro TAS
a. 1950s 1970s: Centralized computers to which the data is brought
b.tories to which sample are brought
(c)
and processed by skilled operators Micro processors (IC) at today.
c. 1900s-2000 : Centralized labora
(b) (a)
(d) (c)
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NTHU ESS5845 Nano/micro Biomecidal and Fluidic System F. G. Tseng Spring/2004, lec 1, p3
and processed by skilled operators LOC or TAS, at today and in the fd. uture
History of Bio Micro systems (courtesy: A. P. Lee)
efore 1990: Petersen at IBM published "Silicon as a Mechanical
ant
n alanalog
2) satisfactorily solve inherent problems of mechanical reliability
3) fabrication process compatible with standard IC processes.Low
ployed. 1982:
so
owe at U.C. Berkeley presents a chemical vapor ra.
f
Other 1980s: the LIGA process by Germans, Wise and Ko continued
1990-1993 (The Renaissance according to A. Manz)
role. E
M evice based on silicon chambers for
B
1982: KurtMaterial" described applications in sensors and actuators. Importdevices were inkjet nozzles, accelerometers, and microrelays. Pointedout 3 major advantages of silicon-based micromachining:
1) provide functions not easily duplicated by conventioand digital circuit.
and reproducibility.
cost, high yield technologies are preferred only if well-established batch fabrication processes areem Masoyoshi Esashi at Tohoku presents work on catheter-tip
pressure sensors. Many packaging techniques [Esashi 1993] are aldeveloped by Esashis group for microvalves and pressure transducers. 1984: Roger Hsensor which initiates the polysilicon surface micromachining eThis transforms into the micromotor and lateral resonators that launched the explosion of MEMS and inspired the imagination omany researchers today.
development of biomedical sensors.
Manz et al. (1990) first proposed the concept of micro total analysis system in which silicon chip analyzers incorporating sample pretreatment, separation, and detection played a fundamental lectroosmotic pumping was an attractive mode of sample transport
when separation was needed iniaturized thermal cycling d
PCR was developed by Northrup et al. and tested HIV, and cystic
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NTHU ESS5845 Nano/micro Biomecidal and Fluidic System F. G. Tseng Spring/2004, lec 1, p4
fibrosis (1995) -1997 Growing1994 to critical mass - The number of published
otides, DNA and amino acids and cell
Microreactors for PCR
Biochips and Microfluidic companies appear (many sprung out of
Affymetrix, Nanogen, Caliper,
ace
BioMEMS drug delivery companies,
1990-2002 b technologies developed:
machining through wafer
Py PDMS, PMMA,
M s and
M ndard micromachining (surface,
MEMS is truly integrated in academics, as almost every disciplinary
A major industries
papers increased abruptly Separation of oligonucle
manipulations.
academia):
Aclara, Fluidigm, Nanostream, Cepheid, Orchid, Biotrove, SurfLogix, Biospect, Micronics
e.g. iMED,MicroCHIPS, Therafuse
key -fa integration of surface and bulk micro
bonding and deep reactive ion etching (RIE) of silicon. olymer microfabrication is foundation of many microfluidics/biochip companies (soft lithographSU-8 etc.), medical microdevices still use a lot of silicon
onolithic and hybrid integration of MEMS and electronic New materials integrated in silicon based processes for sensing
actuating advances (soft lithography, SMA, PZT, smart polymers, porous silicon, etc.)
EMS foundry processes for stabulk, LIGA, polymers)
are getting involved (EE, ME, ChE, Mat. etc) n explosion of MEMS-based companies; many
start exploring MEMS (medical, automotive, biotech, computer, displays, etc), particularly in the optical switch business
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NTHU ESS5845 Nano/micro Biomecidal and Fluidic System F. G. Tseng Spring/2004, lec 1, p5
Alternative names
Micro Total Analysis Systems (TAS)
logy
systems
Review Femmans point view and compared to the goal of NIH,
Feynmans view on Bio micro/nano system:
a. The problems of chemistry and biology can be greatly
b.
Scientific American 2001, 3 visions in nanomedicine:
1. Improve image
Lab on a Chip Bionanotechno Nanobiotechnology Biofluidic Chips Bio Microsystems Bioanalytical Micro
USA
helped if our ability to see what we are doing, and to do things on an atomic level, is ultimately developeda development which I think cannot be avoided Swallowable surgeon
: Improved or new contrast agents would detect
. New ways to treat disease
problems at earlier, more treatable stages. e.g., reveal tumors only a few cells in size
2 : nanoparticles would deliver treatment
plants:
to specifically targeted sites, indluding places that standard drugs do not reach easily. e.g., gold nanoshells that were targeted to tumors might, when hit by infrared light, heat up enough to destroy the growths.
3. Superior im nanometer scale modifications of implant ty
surfaces would improve implant durability and biocompatibilie.g., an atrificial hip coated with nanoparticles might bond to the surrounding bone more tightly than usual, thus avoiding loosening.
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NTHU ESS5845 Nano/micro Biomecidal and Fluidic System F. G. Tseng Spring/2004, lec 1, p6
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NTHU ESS5845 Nano/micro Biomecidal and Fluidic System F. G. Tseng Spring/2004, lec 1, p7
Scale comparison: (courtesy: A. P. Lee)
ano amino acid
DNA helix hannel opening
the major cytoskeletal components)
nm) lysosomes (contain enzymes for many
(1 - 10 m) the general sizes for prokaryotes cell (before-nucleus:
N0.8 nm2 nm diameter of a 2.6 nm diameter of membrane c
4 nm globular () protein
6 nm microfilaments (smallest of 10 nm thickness cell membranes
11 nm ribosome ()
25 nm microtubule (straight hollow cylinders with an inner diameter 15 nm, most rigid of the cytoskeletal organizers and backbone element) 50 nm nuclear pore 100 nm large virus
200 nm (200 to 500
chemical reactions to break down proteins, nucleic acids, sugars, lipids, and other complex molecules) Micro
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NTHU ESS5845 Nano/micro Biomecidal and Fluidic System F. G. Tseng Spring/2004, lec 1, p8
contains no culei and no membrane enclosed organelles)
r power plant)
al cells ()
rog egg
Pharmaceutical industry ental monitoring
Tr hnologies:
Lysing
/biomarkers
on
2 m E.coli - a bacterium
d+a grain, : subcellula3 m mitochondrion (threa
5 m length of chloroplast ()
6 m (3 - 10 micron) the nucleus 8 m human red blood cell
(10 - 30 m) most eukaryotic anim
100 m human egg 1 mm diameter of the squid giant nerve cell 2 mm diameter of a f
Potential applications in:
Military
Environm Medical devices Instrumentation Food monitoring
aditional bioassay tec
Centrifuge
Purification Labeling Extraction Amplification Concentrati Sorting Affinity Assays
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NTHU ESS5845 Nano/micro Biomecidal and Fluidic System F. G. Tseng Spring/2004, lec 1, p9
Components of Micro biomedical/fluidic systems:
cal/biological monitor systems
1. TAS 2. Chemical sensors 3. Chemi4. IT or electronics
Sampling
Sample transportation
Sample collection
Sample treatment
Separation/mixing or chemical reaction
Detection
Data treatment
Interpretation
1
4
3
2
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NTHU ESS5845 Nano/micro Biomecidal and Fluidic System F. G. Tseng Spring/2004, lec 1, p10
Fully Automatic Systems: sensing(input), decision making (IC), actuating (output)
Example: transdermal micro drug delivery systems
. sample preparation
. sample array
g rying
Treatment Methodology in tradition (nanotech 1)
.
the patients medical history, personal line, and current complaints.
123. sample sensing 4. decision makin5. actuating/delive
Six phases in clinical pratice:
1 Examination ()
Examination offunctional and structural base
Classical: interview and observation. New tools for nanomedical testing:
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NTHU ESS5845 Nano/micro Biomecidal and Fluidic System F. G. Tseng Spring/2004, lec 1, p11
surveys laboratory-quality data on the patient
nd solutes,
d. e. ding organelle counts)
messenger
Bi roach: single-molecule DNA assay techniques
billions of nanoscale
. Diagn
nation of the cause and nature of a disease in treatment and prognosis.
s,
3. rogn
ect injury, and of
a. in vivo cytography b. real-time whole-body microbioticc. immediate access to
(blood tests: blood counts, dissolved gases avitamin and ion assays) physiological function and challenge tests tissue composition (inclu
f. quantitative flowcharts of in cyto secondarymolecules
g. extracellular hormones and neuropeptides ological app
(recombinant DNA techniques) Nanomedicine approach: lightwight handheld device consists
a ramifying probe tip containingmolecular assay receptors mounted on hundreds of self-guiding retractile stalks.
osis () 2
The determiorder to provide a logical basis for
In 20th century, diagnoses frequently involved a high degree of uncertainty, largely due to lack of comprehensive molecular diagnostic tools. Diagnosis would be guided by statistical analyses-large uncertainty. Nanomedicine can reduce diagnosis uncertainty by the following possible instruments: a. in-office comprehensive genotyping and real-time whole-body scans for particular bacterial coat markers, tumor cell antigens, mineral deposits, suspected toxinhormone imbalances of genetic or lifestyle origin.
osis () and Treatment () P
Prognosis is a judgment or forecast, based upon a corrdiagnosis, of the future course of a disease orthe patients prospects for partial or full recovery. Treatment: the physicians ability to intervene.
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NTHU ESS5845 Nano/micro Biomecidal and Fluidic System F. G. Tseng Spring/2004, lec 1, p12
ften did
e medical intervention was rational
ble ents.
e
cases of
with a
. Valid
ocedure for eatment was
r are self-curing or
s not
unization programs, amelioration of
res are needed to discover, diagnose,
18th: treatments were almost purely empirical and omore harm than good.
19th and early 20th century: treatments were scientific but largely homeostaticthbut served mainly to assist the body in healing itself. Remaining 20th century: truly curative treatments began to rescue some patients from conditions from which their unaided bodies would not have been able to recover. Early 21st century: Conventional biotechnology will enasome important tissue and cellular replacement treatm
21st century: nanomedicine may enable major reconstructivand restorative procedures at the tissue, cellular and molecular levels and will employ active antibiotic devices.the prognosis will almost be good, except insevere neural damage and a few other specialized circumstgances. Therapeutic treatment will be selected to reverse all pathological effects of disease or injury,minimum of pain, discomfort, side-effects, intrusiveness andtime, and with a maximum of effectiveness, efficiency, andlikelihood of success. It can also correct molecular defects.
ation () and Prophylaxis () 4
A proper therapeutic protocol will include a prfollow up to ensure that the prescribed trcorrectly executed with good results. Often neglected for saving cost because 80-90% of all illnesses which take patients to the doctoself-limiting. (for example, common cold)treatment ito provide a cure, but rather to speed the healing process, improve comfort, and avoid complications. Nanomedical treatments will require supervision and run quickly to completion.
Prophylaxis is the prevention of disease, typically includingpatient education, immoccupational hazards. nano/micro scale tools are required for a. Preventative procedu
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NTHU ESS5845 Nano/micro Biomecidal and Fluidic System F. G. Tseng Spring/2004, lec 1, p13
ases, and a variety
b.
Micro s e (research examples)
2. Drug screening (microarray)
and treat apparently symptomless diseof molecular-based physiological malfunctions and structural micropathologies. Ongoing supervisions and adjustment (for example:hormone balance)
ystems in life scienc
1. Examination and diagnosis (loc, utas, array)
i-STATs handheld clinical analyzer and
disposable cartridge
Biolsensor cube and
ogixs pH
Porton Diagnostics potassium sensor and reader
reader
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NTHU ESS5845 Nano/micro Biomecidal and Fluidic System F. G. Tseng Spring/2004, lec 1, p14
3. Drug delivering (LOC, utas)
Micorpump drug delivery system, Debiotech, Sitzerlad
5. In vivo monitorin
4. Sequencing of bio molecules
Streched S-D
SiO Si
DNA PCR
C C D
DNAg (neuro probe, well, bioe
NA
Optical fiber
Transparent peak
3 4
2
lectri
0 bp/s:100cal interface)
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NTHU ESS5845 Nano/micro Biomecidal and Fluidic System F. G. Tseng Spring/2004, lec 1, p15
Optical Spectrum Analyzer (OSA)
IgG
Au
COOH-Thiol
EDC /Sulfo-NHSCy
3 Anti-Rabbi
t
PDMS OpticalFiber R1
R2
I
TNF and receptor (antibody)
Valley shift
SMF
Optical Circula
W toELED / 1550nm / 8uFWHM :150nm
Current Controller
SMF
Sensing Fiber
Electrochemcial sensor/electrodes for stimulation
Integrated needle/fiber
immunosensors/drug delivery system
Fiber bundle 1 m
Drug delivery system
m rInput
Ot
utpu
1 2 3 Output Bare Fiberconnecto
r
Input
Nanomedical Perspetive (nanotech 1)
BioMEMS or Nanomedical instrumentalities should not
significantly alter the classical medical treatment methodology, although the patient experiences and outcomes will be greatly improved.
Treatment will become faster and more accurate, efficient, and effective.
1. Nanomedicine and Molecular Nanotechnology
A mature nanomedicine will require the ability to build structures and devices to atomic precision, hence molecular nanotechnology and molecular
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NTHU ESS5845 Nano/micro Biomecidal and Fluidic System F. G. Tseng Spring/2004, lec 1, p16
manufacturing are key enabling technologies for nanomedicine.
Top-dow vs. bottom-up approach:
Top-down: 1960s-1970s, increasing precise machining and of materials, progressing from large
to smaller scales and ultimate to nanoscale tolerances.Richard Feynman.
ttom 0s-1990s, molecular manipulation and
ild o achines and molecular devices ecision.---K. E. D (settling the term of molecular
n approach
finishing
r
Bo -up: 198molecular engineering in the context of bu ing m
with atomic prlecular m
rexler.nanotechnology in 1991, molecular machine systems in 1992)
Note: this approach is differe from nanostructured bulk materials,
romachinery, polymeric self-assemblnology, nanolithography,
Langmuir-Blodgett thin films Definition of Molecular nanotechnology
nt
micp
y, ure biotech
by Drexler: The control of atomic and
molecular structure to create materials and devices with
three-dimensional positional
molecular precision. Vision of Molecular nanotechnology by Drexler: ---require molecular assembler (10-15 years from nonanomedicine may emerge by 2020.
w),
chines: ral immune system, cell herding
machines:stimulate rapid healing and tissue reconstruction, cell repair machines: genetic surgery.
. Paths to nanomedicine:
BioloUsin g tools to build
Possible applications: programmable immune masupplementing the natu
2
gical approach: the wet process g biological engineering/genetic engineerin up micro/nano biorobots: such as
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NTHU ESS5845 Nano/micro Biomecidal and Fluidic System F. G. Tseng Spring/2004, lec 1, p17
At m cui. Determining or designing the DNA sequence for the genome. ii. Syniii. Introducing the
host cell, then in
At Celiv. Design enzyme
ole lar level (Glen A. Evans, 1998):
thesizing and assembling the genome synthetic DNA into an enucleated pluri-potent
troducing the host cell into an organism.
l levels (by Nonaldson, 1976): s to produces specific repair functions: tured proteins, joining broken lipoprotein aling broken strands of DNA or RNA, rng or special types onto RNA and replica cell the ability to metabolize new substrates, rs, or construct ess
renaturing denacomplexes, anne eading proteins of existi ting them, and givinguse novel cofacto ential amino acids.
v. Spe ially constrc ucted bacteria or microphages able to ead through a specific target tissirs according to the programs designed intoOperate at unnatural temperatures o pathways not present found in na
replicate themselves, dspr ue, and carry out specific repa their DNA/RNA r to utilize metabolic ture.
vi. Re-introduce lost DNA or lost organelles, or introduce entire new
vii. Modi forms of organelles.
fy at will the development of a cell. ir bacteriaviii. Repa able to work together to apply optimal to every body cell. repairs
At whole o
i. Undrganism levels(by Nonaldson, 1976): erstanding the physiology of aging combined with the
ii. Conorg
iii. Nokeep a given tissue alive and healthy in vitro for an
mporary replacements for any body organ which may have been lost.
=> w
Mechanical approach: the dry process
ability to reverse it. trol over growth and development: grow of new ans/tissues npermanent substitute organs for (a) the ability to
indefinite time (b) te
hole body repair
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NTHU ESS5845 Nano/micro Biomecidal and Fluidic System F. G. Tseng Spring/2004, lec 1, p18
mic precision.
1959, Richard Feynman: It does not violate any physics
ne
sensors, programs,
nents of individual cells.
Nanotechnology
T ranches of nanotechnology for
Artificially fabricate nanodevice with ato
i. Is it possible? 1952, Erwin Schrodinger:we would never experiment with just one electron, atom, or molecule
laws. ii. Feynmans view on nanomedicine:
a. The principles of physics, as far as I can see, donot speak against the possible of maneuvering things atom by atom. It is not an attempt to violate any laws; it is something, in principle, that can be done; but practice, it has not been dobecause we are too big.
b. top-down processleading to todays Micro Systemtechnology, and nanotechnology
c. Swallowable surgeon
iii. Drexlers vision: a. bottom-up process b. cell-repair machines: combines
and molecular tools to examine and repair the ultimate compo
3. Comparison of Biotechnology and Molecular
hree contemporary bbiomedical application:
Nanoscale materials technology: biocompatible materials aalytical techniques, surgical and dental practice, nesearch using intracellular electrodes, biostructures search and biomolecular research
nd an rve cell rere using intracellular electrodes, biostructures research and biomolecular research
tical microscopy, scanning-probe microscopy and optical tweezers, and vaccine design, bulk
and classical
using near-field op
chemical and biochemical manufacturing,pharmacology.
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NTHU ESS5845 Nano/micro Biomecidal and Fluidic System F. G. Tseng Spring/2004, lec 1, p19
Biotechnology: an established medical capability, many applic Molec
ations and products in the market.
ular nanotechnology: The engineering of all complex mechanical systems constructed from the molecular level.
Advantages of molecular nanotechnology: i. speed of medical treatment
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NTHU ESS5845 Nano/micro Biomecidal and Fluidic System F. G. Tseng Spring/2004, lec 1, p20
e nical therapeutic
systems can be expected 103-105 faster.
sec, but mechanical nanomanipulators can operat4e at 1-10 cm/sec, a 4-5 higher orders of magnitude. Strongest biological fibers (e.g. intermediate filaments) have a failure strength 3 orders of magnitude below the strongest mechanical fibers (fullerene nanotubes)
systems may employ simple cable-pulling, winches(), or ratchets (), much faster and direct. Muscle contraction is irreversible and can not generate power, but electric motor can be power generator, loudspeakers can be used as microphones.
.
e strengths
Dermal wound repair via natural fibroblasts may requirweeks to run to completion, but mecha
Because of: Typical fibroblasts movements occur at 0.1-1 microns/
Biological cilia beat at ~30 Hz while mechanical nanocilia may cycle up to ~20 MHz, (but in pratical~10 kHz.)
In either biological or mechanical systems, large numbers of devices of comparable physical size (e.g. ~microns) may be employed to do the work, so numbers alone cannot offset the mechanical speed advantage.
ii. power density and transduction
Biological cell typically employ power densities of 103-104 W/m3, with maximum densities of ~106 W/m3 in honeybee flight muscle cells and bacterial flagellar motors. Nanomechanical power systems can produce power densities of 109-1012 W/m3.
Conducting polymer-based actuators generated 20-100 times the force for a given cross-sectional area as mammalian skeletal muscle.
Amoebic locomotion in motile cells requires diffusion-limited cytoskeletal disassembly and reassembly to achieve movement, mechanical motility
iii superior building materials Typical biological materials have tensile failur
in the 106-107 N/m2 range, compare to 109 of steel, 1011 for
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NTHU ESS5845 Nano/micro Biomecidal and Fluidic System F. G. Tseng Spring/2004, lec 1, p21
iv. Nondegradation of treatment agents v. C trvi. Nanovii. Avoviii.ix. Morx. Morexi. R uxii. Assu
4 Examples 1. DNA nanopore technology: Coll ies and Harvard University nanopor eqelectronic sigindividual, c eds and for a low
diamond.
on ol of nanomecial treatment device versatility
iding overspecialization Faster and More Precise diagnosis
e Sensitive Response threshold for high-speed action reliable operation
ed ced replicator danger red patentability
for bionanotechnology
aboration between Agilent Technologe s uencing converts nucleic-acid sequences directly into
natures and could make it possible to easily sequence hromosome-length molecules of DNA at very high spe cost
2. Quantum
dots:
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NTHU ESS5845 Nano/micro Biomecidal and Fluidic System F. G. Tseng Spring/2004, lec 1, p22
Latex beads filled with quantum dots, Scientific America, Sep. 2001
ons,
on with organic dye and bulk semiconductors:
excitation emission
Organic dye: single single Bulk semi. : multiple single (band gap) Quantum dot: multiple single (size)
=>a single type of semiconducting material can yield an entire family of distinctly colored labels
signal would not decay after multiple excitation
. color can be custom-built, almost no limitation on color types and numbers.
. Exited color is very uniform.
A. Paul Alivisatos, a. Developed since 1970, originally for optoelectronics applicati
but now with high potential for disease diagnosis and drug screening.
b. The comparis
c. d
e
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NTHU ESS5845 Nano/micro Biomecidal and Fluidic System F. G. Tseng Spring/2004, lec 1, p23
3. Nano drug delivery system
Mauro Ferrari, Mechanical Engineering, Dec. 2001
remarks
integrated circuits cessors are ubiquitous stics to environmental
chronic
olecular processors requires training of a new
generation work force
atures: Journals:
romechanical Systems, IEEE/ASME joint publication (ISSN 1057-7157), quarterly from March 1992. JMM: Journal of Micromechanics and Microengineering, American Institute of Physics (ISSN 0960-1317), quarterly from March 1991.
rs A and B, Elsevier Sequoia (ISSN
Conclusion
1. Integrated microfluidics has the potential to rival
2. Applications for biomolecular proranging from point-of-care diagnosensing, from acute (combat casualty care) to (early detection of cancer)
3. Design tools are necessary to predict complex behavior and allow biologists to become chip designers
4. The development of biomthe multidisciplinary (Bio:Info:Nano)
Related liter
JMEMS: Journal of Microelect
S&A: Sensors and Actuato
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NTHU ESS5845 Nano/micro Biomecidal and Fluidic System F. G. Tseng Spring/2004, lec 1, p24
0924-4274), 5 Vol. Per year, 3 issues per volume.
, Japan
,
ConferMEMS##: IEEE Micro Electro Mechanical Systems 1987 and annual form 1989, held in February (Abstract due in Sep.)
E winter annual meeting Annual (MEMS symposium from 1990), in Nov/Dec (Abstract due in Feb.) Trans e actuators (T ial from 1981, in June (Abstract due in Dec.) HH##: IEEin June (AbSPIE##: In ngineering, conference for MEM EURO senActua #Harmst'##Nanotech#IEEEnano##:
Referen 1. Robe , Landes
Bios2. Micr McGraw Hill,
19983. Greg 9.
LOC:Lab on a Chip, Royal Society of Chemistry S&M: Sensors and Materials, Scientific Publishing Division of MY(ISSN 0914-4935). 6 issues per volume. B&B: Biosensors and Bioelectronics, Elsevier Science (ISSN 0956-5663), 12 issues per year from 1986 BM: Biomedical Microdevices-BioMEMS and Biomedical NanotechnologyKluwer Academic Publishers (ISSN: 1387-2176), 2 issues per year from1999. MST: Micro system Technology, Germany. Nanotechnolgy, Institute of Physics IEEE Transactions On NanoBioscience, IEEE.
ences:
ASME IMECE: ASM
duc rs##: International Conference on Solid-State Sensors andransducers xx) bienn
E Solid-State Sensor and Actuator Workshop, biennial from 1984, stract due in Jan.) ternational Society for Optical E
S or Optical MEMS, annual sor
tor' #, Europe conference , follow transducer #:
ces:
rt A. Freitas Jr., Nanomedicine volume I: Basic Capabilitiescience, USA, 1999. omachined Transducers source book, Gregory T.A. Kovacs,. ory Timp edited, Nanotechnology, AIP press, 199
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NTHU ESS5845 Nano/micro Biomecidal and Fluidic System F. G. Tseng Spring/2004, lec 1, p25 4. Davi re, Wiley-Liss, 2004. 5. A. P.6. Fan-
d S. Godsell, Bionanotechnology, lessons from natu Lee, class notes of UCI BME295. Gang Tseng, research proposals.
Micro