Modular, Polymeric Development Platform for Microfluidic Applications

- Design, Fabrication, Testing and Examples

Proyag Datta

PhD Thesis Presentation

Microfluidics for Bio-MEMS Applications

�  MEMS sensors for analysis of biological elements

�  Applications ◦  Healthcare ◦  Defense ◦  Environment

�  Critical Aspects ◦  Low Cost – Disposable ◦  Polymers ◦  Multi-domain Technology

�  Bio-chemistry �  Microfluidics �  Electronics

�  Transition from prototype to Mass Production

I-Stat®

ICs, Diode, Transistors

TV, Radios Computers

Prototype PCBs,

Breadboard

Mixers, Splitter, Pump,

Agilent Bio-Analyzer,

I-Stat

Components

System

Development Platform

Micro-Electronics Microfluidics

Analogy between Micro-Electronics and Microfluidics

Missing Link : A development platform for Microfluidics

Outline of this Presentation

q  Concept q  Fabrication

q Mold Insert q Hot Embossing q Post Processing

q  Applications q Surface Chemistry q Optical Waveguide q Protein Crystal Formation

Thesis Goal: Design, build and test a general purpose microfluidic development platform

q  Flexible q  Compatibility q  User Friendly q  Modular q  Rapid Fabrication q  Low Cost

Development Platform

Platform Concept – Specifications

Input Sample

Preparation

Reaction/ Processing/ Separation

Detection/ Analysis

Output

Platform Concept §  Individual functional chips §  Vertically assembly = Minimal dead volume §  Passive Alignment of Chips §  Electronics integration §  Compatible w/ existing labware §  Macro-Micro interconnections standardized

Clamp

Alignment Pins

Electronic Connector

Fluid Distribution Backplane

Nozzles

Syringe Ports

Structural Block

Modular Microf luidic Chip (MMC)

Elements of Interconnect Block (ICB)

Electronic Interconnect Macro-Micro Fluidic Ports

Alignment Features

Alignment Verification Window

75.5 mm

25.5 mm

Region for Fluidic Layout

Hot Embossing

Jenoptik HEX02 Hot Embossing Machine at CAMD

Mold Molded Part

LiGA

Micromilling

50 µm dia.

Criteria • Cost • Turnaround Time • Surface Finish • Minimum feature • Geometry

Parameter Evaluation Curve

Brass mold insert and molded chips on the bottom platen of molding machine

T>>Tg

T<<Tg

T~Tg T>Tg

80 100 120 140 160 180 200 Temperature (°C)

D

ispl

acem

ent

(mm

) -0

.5

0

0.

5

1.

0

1.5

2

-­‐0.5

0

0.5

1

1.5

2

2.5

3

3.5

70 90 110 130 150 170 190

Displacemen

t  (mm)

Temperature  (°C)

T~151°C

T~162°C

T~175°C

Incomplete filling in corners

Completely filled structure

Process Bias of Hot Embossed Parts

Full factorial design of experiment (DOE) based study to evaluate dimensional variation as a function of process parameters. (32 molding runs, 4 data points per part = 128 Total data pts)

Newton Thickness in mm Distance from Center (mm)

Dim

ensi

onal

cha

nge

in m

m

Celsius Celsius Seconds

Dim

ensi

onal

cha

nge

in m

m

Post-Processing

Cut

Snap-off or dicing location

Flycutting Tool

Overall dimension of part independent of cutting operation

Through-holes opened

Thickness control to within 10µm

Snap-off Boundary Structure

Molded Chips before Processing Chips being flycut Chips after flycutting

500 µm dia through hole opened by flycutting

Passive Alignment - Concept

Clamp with dowel pins

Stack of chips

V-grooves

Acceptable Unacceptable

Vias from one fluidic chip to next

Alignment Fixture

Alignment Verification Window

75.5 mm

25.5 mm

Passive Alignment - Accuracy

0

0.02

0.04

0.06

0.08

0.1

0.12

0   5   10   15   20  

Mill

imet

ers

Assembly Attempt

Alignment of 4 Chip Sets

Overlaid Alignment Marks

Nominal 100 µm

Chip2

Chip1

35

40

45

50

55

60

65

70

1 2 3 4 5

Ave

rage

Alig

nmen

t Acc

urac

y (m

icro

ns)

Square root of the number of contacts

Chip Stack Alignment Marks

100µm gaps

Chip Sealing

Cross Section of Sealed PMMA Chip (110 °C , 60 to 70 psi pressure, 1 hr)

q  Temporary Gasket (Open Access) q  Permanent Seal

q Sealing Methods q  Adhesive q  Laser q Ultrasonic q Thermal Sealing

Standalone thermal sealing press

100 µm

Hardware

Fluidic chip with electrical lines and macro connector

Microfluidic chips with the fluidic macro connector block

Sealed fluidic chip

Multimeter connected to the flat ribbon cable

Flat ribbon cable to interconnect stack and measurement devices

 

Fluid In

Fluid Out

 

Nozzles to Interconnect Chip

Fluid route from Syringe inlets to chip stack

Bolt Holes

Hardware

Fluidic distribution manifold (backplane)

Modular Microfluidic Chip Stack

Biochemical Protocol on Silicon Chips

Chemilumenscent signal captured on X-ray film. Chips with 1:10 serial dilutions of protein conjugates, Strepavidin – Horse Radish Peroxidase(S-HRP) were placed in different chambers with the far right being the highest concentration of S-HRP.

Bio-chemistry experiments on silicon surface in a microfluidic environment Open access to chips for Microspotting

Application - Optical Waveguide q  Waveguides used to excite

fluorescent probes and detect the emitted light

q  Goal : deliver excitation light to an extended/wide region, such as a microfluidic channel, exciting all fluorescent probes therein

Microscope objective

Excitation Light

Fluorescent Probe

Filters

CCD Camera

Emitted Light

To Computer

Light in

Light out

Light leaking into the channel

Working of the waveguide

Light emitted from Fluorescent probe

Floor of Microfluidic channel contains light by total internal reflection

Microfluidic channel Light ‘leaking’ into microfluidic channel

Fluorescent probe attached to DNA

Air

Air

Application - Optical Waveguide

Waveguide

Fluidic Channel Top mold insert

Bottom mold insert

Micro fluidic channel

Polymer

Air

Fabrication of chip by double sided aligned molding

Image of Fluorescence Excitation using embedded waveguide

Cross- section of chip

0 4 8 12 16 201000

1250

1500

1750

2000

Fluo

resc

ence

Inte

nsity

Distance from the beginning (mm)

Fluidic Channel

Laser Diode

Microscopic objective

Filters

PMMA chip

XYZ Translation Stages

Optical fiber

CCD Tube

Coupling

Application – Protein Crystallography

Oil Precipitant

Protein Electronic Wiring for feedback

Interconnect Slide

Removable Storage Slide

Diff

eren

t pro

porti

ons o

f m

acro

mol

ecul

e an

d pr

ecip

itant

mix

Protein MoleculesPrecipitant

Separating fluid (oil)

Real time X-ray Spectroscopy of Nanoparticles Creation Chemistry

Controlled Cell Growth

Other Applications

X-rays from Synchrotron Beamline

Detector

Reagents

Product

Microscope

Alignment Optics

Summary �  Microfluidic Development Platform ◦  Vertically stacked ,Modular chips ◦  User friendly ◦  Compatible w/ Standard Labware

�  Fabrication Technologies ◦  Mold insert ◦  Hot embossing ◦  Post Processing

�  Applications ◦  Bio Protocol ◦  Waveguide ◦  Protein Crystallography

Outlook Integration of Discrete Components q  Electrodes q  Electromagnets q  Piezo electric actuation q Reactor beds q Heaters / Coolers q  CMOS & other silicon die

Integrated System Development using the

Microfluidic Development Platform

Modular Microfluidic Development

Platform

Increase Functionality

Specific Applications

Thank You !