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BIOMICROFLUIDICS

May 12, 2003

Final Report

www.mae.ufl.edu

Susan Beatty Stacy Cabrera

Saba Choudhary Dan Janiak

OVERVIEW

This illustration show the processing of a glass microfluidic device.

http://www.mae.ufl.edu/~zhf/Resear chInterests-ZHFan.htm

• Microfluidics

Introduction

• Biomicrofluidics

– Lab-on-a-chip

– Drug delivery and

Micro-dosage systems

•Materials

–For Microfluidics

–For valves

•Processes

–For Microfluidics

–For valves

•Future of Microfluidics

MICROFLUIDICS

• The control of tiny amounts of gases or liquids in a miniaturized system of channels, pumps, valves, and sensors.

• The motivation stems from trying to be more efficient on a smaller scale (several tests on a single micro chip).

• Example in Nature: human body’s oxygen (blood) transport system

• mTAS: systems of channels, valves, pumps, detectors

MOTIVATION

• Macro scale = laminar, random, and turbulent flow

• Micro scale = laminar flow

• Laminar flow allows controlled mixing

• Low thermal mass

• Efficient mass transport

• Good (large) ratio of channel surface area: channel volume http://www.spie.org/web/oer/august/aug00/microfluidics.html

BIOMEDICAL APPLICATIONS:

LAB-ON-A-CHIP

•Used for analyzing thousands of samples at once

•Can perform clinical diagnoses, scan DNA, run electrophoretic separations

•System: substrate with integrated microchannels and devices

•Experiment: uses fluid sample in picoliter range

•Advantage: conserve sample and time

LAB-ON-A-CHIP: GENE CHIP

•Also known as DNA chips or DNA microarrays

•Used for analyzing thousands of Genes at once

•DNA probes and DNA sample

•Can analyze cancerous cells

•Can determine which genes or turned on or off by a drug

•Advantage: accelerate the pace of genetic research

GENE CHIP

http://www.popcouncil.org/images/gene_chip.gif

BIOMEDICAL APPLICATIONS: DRUG

DELIVERY AND MICRO-DOSING

SYSTEMS

•Needed in the medical field

•System: micropump and flowsensor

•High dosage approach used in the past

Insulin – wastage of insulin

Painkillers – possibility of addiction

•Insulin micropump: mimic action of pancreas http://www.yourmedicalsour

ce.com/images/pancreas.jpg

Microfluidics can make possible closed-loop system with glucose sensor

•Painkillers: deliver drug locally, not globally

Avoid addiction

Tested at Maternity Hospital in Dublin, Ireland

DRUG DELIVERY: NEURO-

ACTIVE COMPOUNDS

•Current research at Michigan

University on Neural Microfluidic

Devices for the intracerebral delivery of neuro-active compounds

•Challenge: Must get the drug to CNS, across blood-brain barrier and before drugs are degraded and metabolized

•High dosage approach can have detrimental effects on other parts of http://www.yourmedicalsource.com

/images/central_nervous_system_4

00.jpg

body

•Challenge can be faced with microfluidic technology

MICROFLUIDIC SYSTEMS:

PRODUCT OF DEVICE

INTEGRATION

•Many micro-devices: valves, pumps, fluidic mixers, and sensors

•Device focus: Valves – needed to control flow of fluid

•Two types of Valves: Passive and Active

PASSIVE VS. ACTIVE VALVES

Passive Valves

No actuation required

Designed to give higher flow in one direction

Main application in mechanical micropumps

Flap is controlled by pressure difference across it

Active Valves: Slightly more complex

Need a form of actuation (thermal, electrical)

Actuation controls the flap

MATERIALS OVERVIEW

The type of material used depends on the structure or device

(mircochannel, pump, valve, etc…) being fabricated

-cost -compatibility

MATERIAL

POSITIVES

NEGATIVES

SILICON

Well understood

Highly available

Expensive

Not always bioinert

PLASTICS

Inexpensive

Disposable

Easily machined

Swelling

Pairing

COMMON MATERIALS

-

-

-

PDMS – Polydimethylsiloxane

Used as a structural material for microchannels

Low interfacial free energy

Stable against humidity, temperature

Can be used as a stamp for processes such as microcontact printing, micromolding

Parylene

-

Can be used as a structural material or coating

Low permeability to moisture

High resistance to corrosion

Polyimide

Used for microchannels

Easy to deposit metals (sputter)

MATERIALS FOR VALVES

Conjugated polymers

•“Organic semiconductors”

•Doping level depends on the oxidation state of the polymer

•Volume change associated with oxidation state

•Volume change occurs as a result of ions moving into and out of the polymer

Large Immobile Anion: Small Mobile Cation:

P + (A ) + C + + e 

P

(AC) P + (A ) + C + + e 

P

+ A + C +

MATERIALS FOR VALVES

PEG (Polyethylene Glycol)

•Volume change associated with phase transition

Paraffin

•Volume change

Bimetallic Strips

•Expansion http://www.wam.umd.edu/~smela

PROCESSES

• Overview

– Soft lithography

• Silicon is patterned with a negative photoresist

• Polymer is cast onto silicon mold

• Polymer is cured and removed from mold http://nanotron.ecn.pudue.edu

PROCESSES CONT.

– micromachining

• Bulk micromachining

– Removes from bulk of material-etching

• Surface micromaching

– Adds to surface of material

» Deposistion

» Micro contact printing

VALVE PROCESSES

• Diaphragm check valve http://touch.caltech.edu

http://gmwgroup.harvard.edu

• Begins with etching holes into silicon substrates from bottom

VALVE PROCESSES CONT.

• Metal seals are deposited

• Photoresist and polymer are deposited

• Resist is removed with acetone and silicon membrane is etched http://touch.caltech.edu

FUTURE OF BIOMICROFLUIDICS

• Automation of complex experimental procedures

• Transformation of macroscale lab tests to a device the size of a postage stamp, available to the individual, with the skill of the technician

• More rapid DNA sequencing and general biological procedures

• Key Factor: future fabrication techniques are compatible with current batch processing techniques

Small ridges along the channel walls can force mixing by a kneading motion, http://depts.washington.edu/bioe/shrunklab.pdf.

QUESTIONS

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