Microsystems engineering at the interface of physics biology and...

© A.G. Andreou 1ISR, University of Maryland College Park, 12/04/2007

Andreas G. Andreou

Electrical and Computer Engineering andWhitaker Biomedical Engineering InstituteJohns Hopkins University

Microsystems engineering at the interface of physics biology and chemistry


• Introduction– hybrid microsystems (I): why?– emerging technologies– hybrid microsystems (II): how?

• Integrating Nano, Micro and Macro – u-incubator– and beyond

• Concluding Remarks

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Hybrid MicrosystemsComplex structures at the interface of physics, chemistry and biology

How: Multidomain and multiscale integration from nano to micro and macro using both top down and bottom up fabrication methods.

solid, liquid and gas or vapor stateelectromagnetic and electromechanical

organic and in-organicCMOS and other material systems

electronic and ionicliving and non-living

Why: Increased structural complexity to attain improved performance / higher system functionality and or lower cost.


biotechnology applications

• Stem cell research• Viral transfection• Gene therapy• Nanoparticle drug delivery• Monitoring intra/intercellular

signaling pathways• Biosensors for hazardous

substance monitoring





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Quantum ComputingDNA Computing

Quantum Cellular Automata

Self AssemblySoft Lithography

uFluidics

Single Quantum FluxElectron Interference

Spintronics

Carbon NanotubesMolecular Devices

Coulomb BlockadeInterband Tunneling

Resonance TunnelingGiant Magnetoresistance

Plastic ElectronicsPhotonic Crystals

Emerging

Technologies

nano-CMOS SOI-CMOS3D-CMOS

Microsystems


silicon CMOS

Human Hair

100μm

100000000 X1 nm

L

P-substrate(Bulk)

Gate

Gate Oxide

B

SourceDrainG

D

S

10 nm

MOS transistor500 nm

Blue

Human Cell

10 mμ


• Optically transparent

• Electrically insulating

• Stable to chemicals

• Bio-compatible

• 50 times cheaper than silicon

silicone: PDMS poly-(dimethylsiloxane)

CH3CH3

SiO

SiO

CH3CH3

n


PDMS Fabrication Replica Molding

Y. Xia and G. Whitesides, “Soft lithography,” Angewandte Chem. Inte. Ed., vol. 37, no. 5, pp. 550–575, Dec. 1998.S. Quake and A. Scherer, “From micro to nanofabrication with soft materials,” Science, vol. 290, no. 5496, pp. 1536–1539, Nov. 2000.


soft-lithography and replica molding





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micro-electronics scaling: Moore’s law

Electronics, Volume 38, Number 8, April 19, 1965

1. More transistors per unit silicon area2. Lower energy costs for computation

Intel Core 2 Duo “Extreme” CPU

200,000,000 components


micro-fluidics scaling: Moore’s law no more


MICROFLUIDICS

a new paradigm for integration

“Fabrication of a single 2 gram silicon DRAM microchip requires 32kg of water and 41MJ of energy and produces 1.7kg of waste”

E. Williams and R. Ayres and M. Heller, Environmental Science and Technology, 2002


system architecture

Highly FunctionalReusable Components

Reconfigurable

Low Cost

Environmentally Friendly

Simple, Low-CostDisposable Components

Actuation

Sensing

Feedback





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cell culture today

Incubator FlaskPhotography by Andreas Andreou


1882 – beating heart in salt solution, Sydney Ringer

1885 - embryonic chick cells maintained in vitro, Wilhelm Roux

1907 - in vitro tissue culture (nerve growth), Ross G. Harrison, Johns Hopkins University

history of cell-tissue culture and incubation

the growth of cells derived from

living tissue in an artificial medium

WasteIncubatorCulture Flask

Computer DAQ Chip-Scale Incubators

our goal


Kovac and DeBusschere, Proceedings of the IEEE, June 2003

2 hours in ambient environment

the state of the art


History Cell/Tissue Culture


• Microfluidic Geometry

• Diffusion

• Fluid Flow and Volume

• Thermal Characterization

• On-Chip Electronics Design

• Electrical Interface

Conditions for Cell Growth

Asepsis

Oxygen Supply

Culture Medium

Temperature


Hybrid Microsystem: Micro-Incubator (I)

© A.G. Andreou 25ISR, University of Maryland College Park, 12/04/20071. DPDMS= Diffusivity of Oxygen through PDMS

PDMS

Cellular Oxygen Supply: A Balancing Act

PDMS

culture well

atmosphere

Maximum Oxygen Consumption1.00 x 10 -16 mol

cell x sec

Atmospheric Oxygen

Rate of Oxygen Diffusion through PDMS

Flux = DPDMS

1 x Δ Cthickness


heating and temperature measurement (I)


heating and temperature measurement (II)

Thermistor

Heater

PTAT


Front Back

Finite Element Analysis

Empirical DataEmpirical Data

Finite Element Analysis


Empirical Thermal Testing Setup

1. USB-TEMP with cold junction compensation

2. Small (40) gauge thermocouple

3. Micro-Incubator

4. XYZ stage micromanipulator


packaging: what works! (I)

2.9x10-9 W/m2


why the obvious does not work!

1.8x10-5 W/m2


hybrid microsystem: micro-incubator (III)

J. Blain Christen and A.G. Andreou, “Design, fabrication and testing of a hybrid CMOS/PDMS microsystem for cell culture and incubation,” IEEE Transactions on Biomedical Circuits and Systems, Vol.1, No. 1, pp. 2-14, April 2007


hybrid microsystem: micro-incubator (II)


micro-incubator architecture


BHK: fibroblast morphologywhat healthy cells look like!


cell growth in micro-incubatorchip version 1

42 hours 60 hours


72 hours (3 days)

cell growth in micro-incubatorchip version 2





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Devices ArchitectureNetworks

molecules macromoleculescells

nano-CMOS nanowiresribbons

Self-assembly

Energy

Information (human insight)

Adaptation and Learning

beyond the u-incubator (I)


beyond the u-incubator (II)

• Temperature Dependent Assay– Heater array chip1 for

addressable temperature control

• Optical Assay– Imager array– Optical filtering needed for

many applications

1 “CMOS Heater Array for Incubation Environment Cellular Study”, J. Blain Christen and A. Andreou, Proceedings of the 48th Midwest Symposium on Circuits and Systems. 2005


wireless communication (I)

Signaling Platform – Control and Gather Data

USBRFID Tagged Array


wireless communication (II)

Signaling Platform – Control and Gather Data

USB

Microfluidic Device Array


3D CMOS

MIT Lincoln 3D 180 nm SOI CMOS technology

50nm

JHU multiproject site

Imager Integrated Interferometer


3D CMOS activestructures design

(top down)Self Assembly (bottom up)

complex 3D matter: bottom up and top down


Thermal Control Mechanical Stimulation

OpticalInput

Electrical Stimulation& Recording

Cell Culture

OpticalDetection

3D hybrid integration


self-assembly (II)


cell to cell (micro and nano)chip to chip (micro and nano)MOSFET to

MOSFET(nano)

hybrid matter

energy supply optical and radio frequency photons (macro and meso) chip to virus to cell to

chip (micro and nano)

macromolecule to macromolecule(nano)


2007

2027


year 2027Johns Hopkins Medicine, Hospital and associated Medical Institutions have been turned into a historical museum for visitors in Baltimore.

Visitors can get a glimpse of how top tier medical care and research was carried out in the premier research hospital of the Nation back in the 20th century.

• Health care is done at home using patient monitor services and chip level implantable instrumentation, uTAS, and uMRI. Electronically programmed chips control delivery of drugs in a timely and precise fashion.


Acknowledgements

Jennifer Blain Christen, Assistant Professor, ASU

MIT/LL and DARPA, 3D CMOS technologyProf. Sachs and Prof. Elisseeff, cell-culture share facilityNSF grant ECS-0225489, “Cell Clinics On a Chip”NSF graduate student fellowship to JBCIEEE EDS and CAS DLP program


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Microsystems engineering at the interface of physics biology and...

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