Lecture _2 Introduction to BioMEMS _ BioNanotechnology

8/2/2019 Lecture _2 Introduction to BioMEMS _ BioNanotechnology

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Luke P. LeeDepartment of Bioengineering

Biomedical Innovations by BioPOETS*

*BioPOETS

:Bio

logically-inspiredP

hotonics-Optofluidics-ElectronicsTechnology &Science

Lecture 2 Introduction to BioMEMS

& Bionanotechnology


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UC Berkeley

The BioPOETS

Physiologically

Relevant

Fluidic ICsfor Quantitative Cell Biology

and Quantitative Medicine on Chip


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The BioPOETS

Cellular BioASICs*BioASIC #1 Integrated Microfluidic Patch-clamp Array Chip

BioASIC #2 Single Cell Electroporation Chip

BioASIC #3 High-density Single Cell Analysis ChipBioASIC #4 Dynamic Cell Culture Chip for Systems Biology

BioASIC #5 Cell-cell Communication Chip

BioASIC #6 Cell Lysing Devices for Sample Preparation

BioASIC #7 Biomimetic Cell Sorting Microfluidic Devices

BioASIC #8 Micro PALM for Cell ManipulationsBioASIC #9 Integrated Cell Culture & Lysing & Harvesting

BioASIC #10 Biomimetic Artificial Livers on a Chip

BioASIC #11 Biofluidic Self-assembly of Spheroids on a Chip

http://biopoets.berkeley.edu

*BiologicalApplication Specific Integrated Circuits


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Integrated Microfluidic

Patch-clamp Array Chip(IMPAC)

Sigworth, Nature 423, 21-22 (2003)

BioASIC #1


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Mammalian Electrophysiology on

Microfluidic BioASICs* Platform

BioASICs:

Biological

Application

Specific

Integrated

Circuits

C. Ionescu-Zanetti, R. M. Shaw, J. Seo, Y. Jan,

L. Y. Jan, and L. P. Lee (PNAS, 2005)


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The BioPOETS

Simultaneous Electrophysiological

and Optical Measurements


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The BioPOETS

Ion Channel Gating (Kv2.1) Voltage gating Ligand gating


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The BioPOETS

High-densitySingle Cell

Analysis Chip

BioASIC #3


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The BioPOETS

High density Single Cell Array via

Hydrodynamic Single Cell Tweezers


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The BioPOETS


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The BioPOETS

Dynamic Single-Cell Microfluidics

for Long-term Cytotoxic Drug AssayMedia Input Drug Input

Waste Output

Single Cell Culture Chamber

log-gradient

generator

= 9:1Media : Drug


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Physiologically

Relevant DynamicCell Culture System:

Cultural Revolutions

BioASIC #4


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Biomimetic Physiological Microenvironment

Tissue

Size (D) 100-300 m

Circulatory Flow (c) 700 m/s

Interstitial Flow (i) 0.1 m/s

Extracellular Matrix Complex

D

c

i Cell Growth andInterstitial

Space

Cell

Loading

Blood

Flow

Microfluidic

50-1000 m

80-4,000 m/s

0.08-4 m/s

Surface Coating


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Cell Culture Biotechnology

Microtiter

Plate

CSTR

Bioreactor

Microfluidic

Bioreactor

Volume 50 l 2 L 3 nl

Cell Density(v/v) 5%


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The BioPOETS

Uniform Mass Transfer

a


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CHARM* Cell Culture Well

Fig. 1. (a) Brightfield image of a 64 unit microfluidic cell analysis array. Each well has a culture area 200 m in diameter. Amicrofluidic concentration gradient generator is depicted on the left, providing a separate reagent concentration to each row.

The 8 columns are individually addressable. (b) SEM image of a single CHARM culture well with channel height hc = 50 mand ring height hr= 2 m. (c) Finite element simulation of flow rate through the single culture unit. (d) Equivalent circuit model

of fluidic resistances of the single unit microfluidic design.

Concentration

Gradient

Addressable

Channels

b c

Cell

s

Ro

Ro

RoRo

Rr

d

ahrhc

*CHARM: C-shaped High

Aspect Ratio Microfluidic


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Cell Growth

(HeLa Cell, 30 min/frame, 38 hours)


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Quantitative Data

Cell Growth RateCell Attachment

Kinetics

Microfluidic

24 Well Plate


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Cell Types Cultured

HeLa HeLa tumor NIH3T3 Fibroblast

Primary BAECHepG2 Hepatocyte SY5Y Neuroblasts


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IntegratedMicrofluidic

Cell Culture& Lysis on

a ChipJ. Tanner Nevill, Ryan Cooper,

Megan Dueck, and Luke P. Lee

(LOC 2007)

BioASIC #9


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Cell Culture/lysis Platform


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RBCs, fast lysis event t= 60 ms

OH- as Lytic Agent


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Physiologically-inspired Artificial

Liver SinusoidsLee et al., Biotechnology and Bioengineering 97, 1340 (2007)

BioASIC #10


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Liver Micro-architecture

Sinusoid space transports blood to hepatocytes Lined with fenestrated endothelial barrier Hepatocytes form extensive cell-cell contact


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Artificial Liver Sinusoid

Microfluidic endothelial barrier High density hepatocyte culture Continuous flow mass transport

Precision Control ofHepatocyte Loading


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Effect of Hepatocyte Density

Microfluidic culturewithout ECM coating

Spheroid effectpreviously documented

High density = happy cells Low density = dead cells

Collagen coating requiredfor dish based hepatocyteculture

High density loading canrescue viability in absence

of ECM coating


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Multiplexed Primary Cell Culture with

Packing Density & Flow Controls for StemCell & Systems Biology


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OpticalMEMSfor Lab-on-a-Chip


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Microlens Scanner

S. Kwon & L. P. Lee, IEEE MEMS (2001)


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Lab-on-a-chip withCIAs

In-vivo SMM &

SMD Imaging

Microsystem

HTS Genomics & Proteomics

Nano- & Micro-factory

Lab-on-a-chip


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Images from CIA

1 m resolution


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High-content Integrated Quantitative

Molecular Diagnostics: High IQ-MD

Lab Automation: Sample Prep, SMM, & SMD

1mm

Microfluidic Pumps

Cell trapping

In-vivo IRSpectroscopy

Cell sorting by

adhesion

protein

Cell lysing nSERS

Microfluidic interface

Confocal

microscopy

Confocal

nSERS

In-vivo

detection

window

Nanogap

Junction

CIAs

Cellular

Analysis


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Innovative Personalized Medicine

Information Technology

Disposable

Diagnostic

Biochip

Mobile HealthcareiMDs*

BiotechnologyNanotechnology

*iMDs: Innovative Medical Diagnostic Systems


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Summary

Biologically-inspired photonics and optical systems arebeing developed for innovative healthcare systems.

Cellular BioASICs are being developed for quantitativebiology & medicine.

Quantum nanoplasmonic molecular probes, molecularruler, ONCOS (gene regulator & protein expressioncontroller) are developed for molecular/cellular imaging,and quantitative in vivo biology.

Using BioPOETIC 3D packaging, high-content IntegratedQuantitative Molecular Diagnostic (iQMD) system can becreated for future preventive, personalized medicine, andintegrated health & environmental monitoring systems.

Lecture _2 Introduction to BioMEMS _ BioNanotechnology

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