BIOMICROFLUIDICSBIOMICROFLUIDICS

May 12, 2003

Final Report

Susan Beatty Stacy Cabrera

Saba Choudhary Dan Janiak

www.mae.ufl.edu

OVERVIEWOVERVIEW

• 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

This illustration show the processing of a glass microfluidic device.

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

MICROFLUIDICSMICROFLUIDICS

• 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

MOTIVATIONMOTIVATION

• 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

•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

BIOMEDICAL APPLICATIONS: BIOMEDICAL APPLICATIONS: LAB-ON-A-CHIPLAB-ON-A-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

LAB-ON-A-CHIP: GENE CHIPLAB-ON-A-CHIP: GENE CHIP

GENE CHIPGENE CHIP

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

•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

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

BIOMEDICAL APPLICATIONS: DRUG BIOMEDICAL APPLICATIONS: DRUG DELIVERY AND MICRO-DOSING DELIVERY AND MICRO-DOSING

SYSTEMSSYSTEMS

http://www.yourmedicalsource.com/images/pancreas.jpg

•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 body

•Challenge can be faced with microfluidic technology

DRUG DELIVERY: NEURO-DRUG DELIVERY: NEURO-ACTIVE COMPOUNDSACTIVE COMPOUNDS

http://www.yourmedicalsource.com/images/central_nervous_system_400.jpg

•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

MICROFLUIDIC SYSTEMS: MICROFLUIDIC SYSTEMS: PRODUCT OF DEVICE PRODUCT OF DEVICE

INTEGRATIONINTEGRATION

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

PASSIVE VS. ACTIVE VALVESPASSIVE VS. ACTIVE VALVES

MATERIALS OVERVIEWMATERIALS OVERVIEW

MATERIAL SILICON PLASTICS

POSITIVES Well understood

Highly available

Inexpensive

Disposable

Easily machined

NEGATIVES Expensive

Not always bioinert

Swelling

Pairing

The type of material used depends on the structure or device (mircochannel, pump, valve, etc…) being fabricated

-cost -compatibility

COMMON MATERIALSCOMMON MATERIALSPDMS – 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,

micromoldingParylene-         Can be used as a structural material or coating-         Low permeability to moisture-         High resistance to corrosionPolyimide-      Used for microchannels- Easy to deposit metals (sputter)

MATERIALS FOR VALVESMATERIALS 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 VALVESMATERIALS FOR VALVES

PEG (Polyethylene Glycol)

•Volume change associated with phase transition

Paraffin

•Volume change

Bimetallic Strips

•Expansion

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

PROCESSESPROCESSES

• 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.PROCESSES CONT.

– micromachining• Bulk micromachining

– Removes from bulk of material-etching

• Surface micromaching– Adds to surface of material

» Deposistion

» Micro contact printing

VALVE PROCESSESVALVE PROCESSES

• Diaphragm check valve

• Begins with etching holes into silicon substrates from bottom

http://touch.caltech.edu http://gmwgroup.harvard.edu

VALVE PROCESSES CONT.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 BIOMICROFLUIDICSFUTURE 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.

QUESTIONSQUESTIONS