BIOMICROFLUIDICS

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BIOMICROFLUIDICS MEMS
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OVERVIEW
This illustration show the processing of a glass
microfluidic device. http//www.mae.ufl.edu/zhf/R
esearchInterests-ZHFan.htm

• Materials
• For Microfluidics
• For valves
• Processes
• For Microfluidics
• For valves
• Future of Microfluidics

• Microfluidics Introduction
• Biomicrofluidics
• Lab-on-a-chip
• Drug delivery and Micro-dosage systems

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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 bodys oxygen (blood)
  transport system
• Integration systems of channels, valves, pumps,
  detectors

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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

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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

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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

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GENE CHIP
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DRUG DELIVERY
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PASSIVE VS. ACTIVE ACTUATION
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) Actuati
on controls the flap
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MATERIALS FOR VALVES

• PEG (Polyethylene Glycol)
• Volume change associated with phase transition
• Paraffin
• Volume change
• Bimetallic Strips
• Expansion

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VALVE PROCESSES

• Diaphragm check valve
• Begins with etching holes into silicon substrates
  from bottom

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TRANSDUCER

• Transducer
• A device that converts one form of energy into
  another
• Examples Sensors and actuators
• Sensors usually convert
• Actuators usually convert
• Micromachined transducers (MEMS)
• Fabricated using tools and techniques developed
  for the IC industry and /or some techniques
  developed specifically by and for the
  micromachining community

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Sensor classification

• By signal domain
• temperature, heat, heat flow, etc.
• Mechanical force, pressure, velocity,
  acceleration, position, etc.
• Chemical
  , etc.
• Magnetic magnetic field intensity, magnetic flux
  density, magnetization, etc.
• Radiant wave intensity, wavelength, polarization
  phase, etc.
• Electrical
  , etc.
• By an auxiliary energy source
• Passive
• Input energy is converted into the output energy
• Examples
• Active
• Requires external power (excitation signal)
• Examples

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MEMS Definition

• Earlier definition
• A complete unit that contains both electrical and
  mechanical microstructures
• Characteristic features (3 Ms)

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MEMS commercial applications

• Automotive sensors
• Accelerometers, force/torque sensors, pressure
  sensors
• Bio MEMS
• Micro total analysis system (?TAS), DNA
  sequencing chips, clinical diagnostics, drug
  delivery systems
• Chemistry
• Lab-on-a-chip, microreactor
• Optics
• Digital micromirror devices (TI), grating light
  valve (GLV)
• Optical interconnects, switching
• Data storage
• Precision servo, shock sensors for HDD, new data
  storage mechanisms
• RF, microwave for communication
• Micromachined filters, tunable banks
• Mass flow control
• Micromachined unmanned airborne vehicles (UAV)
• Power generation
• Micromachined turbine engines, MEMS power
  generators
• Recent researches
• Harsh environment MEMS, MEMS/nano hybrid system
  (NEMS)

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MEMS Markets
Janusz Bryzek (Sensors and Actuators, 1996)
Projected total semiconductor market 315 B in
2003
Albert Pisanos forecast (DARPA)
14 B in the year 2000
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Scanning Probe Microscope

• It feels a surface.

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The Bio-Cavity Laser concept

• Incorporates cells directly into the lasing
  process.
• A micropump pushed cells through tiny channels in
  the active region of the device.
• The active region is pumped by an external laser
  source
• Data is collected and processed by a
  mini-spectrometer and computer.

www.sandia.gov. News Releases. March 23, 2000
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The Bio-Cavity Laser concept

• Cancer cells contain more protein, and larger
  nucleuses.
• Their additional density changes (by refractive
  index) the speed of the laser light passing
  through them.
• This modulates the effective cavity length.
• Creates a small difference in lasing wavelength

www.sandia.gov. News Releases. March 23, 2000
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Dependence on cell shape

• Dielectric Sphere Case
• ?? is wavelength shift
• ? geometrical factor of the sphere, 1
• n is refractive index
• xln nth 0 of the lth Hankel function
• L is effective cavity length
• p is longitudinal mode index
• d is diameter of sphere

d6 µm (bottom), 10 µm (middle) and 22 µm (top)
From Meissner, et al.
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Microcavity laser including microfluidic channels
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Miniaturized Optics for Imaging Pre-cancer

• Miniaturized Optic Table (MOT)
• Image sensor
• Collector mirror
• Light source
• Scanning grating
• Folding-flat mirror
• Dichroic beam-splitter
• Lithographically printed refractive lenses
• Lean-to folding flat mirror
• Objective lens

C. P. Tigges, et. al., IEEE Journal of Quantum
Electronics 38, 2 (2002).
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Miniaturized Optical Table (MOT)

• Note the silicon spring
• V-shaped channel
• Spring displacement
• Stress in normal direction
• 150?m thick optical element

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Miniaturized Microscope Objective

• Schematic
• Microscope Objective
• MOT micromachined substrate
• Note lenses in slots

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Requirements

• Maintain a low cost for the system
• The complete system will be no more than a cubic
  foot
• Reduce analysis time to around 3min. max
• Low power consumption
• Build durable MEMS
• Distinguishable peaks on a graph (current vs.
  time)

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Electroosmotic Flow (EOF)

• Electroosmotic Flow (EOF)
• Fluid Pumping Technique
• Driving Force ? Electric Fields
• No Moving Parts

Compared with
MEMS Pump
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Capillary Electrophoresis

• Capillary Electrophoresis (CE)
• Ionic Separation Technique
• Driving Force ? Electric Fields

Electrochemical reaction occurs in the presence
of the ions which results in a current spike.
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MEMS Layout
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Fabrication
Fabrication of CE chips in Plastic and Elastomers
1)
5)
2)
4)
3)
Plastic/Elastomer
Silicon
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Control System
ECHEM Detector
Control Logic
Relays
MEMS
Power Supply
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Future Applications

• XYZ System on a chip
• Fluorescence Detection
• CE/EOF Pump
• Driver Electronics
• Applications
• Nanotechnology
• Chem/Bio. Detection
• Cancer Detection
• DNA Arrays
• Microdialysis
• Pharmaceuticals

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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

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My BIOI-MEMS onto Medical Application (I)

• Applications
• Selective Capture of Cells Overexpressing Certain
  Markers
• High Surface Area Class-Selective
  Preconcentration of Targets
• Electrochemical transduction
• Resistless photopattern electronics on Polymers
• Incorporating sub-micron structures in
  microfluidic networks
• Non-mechanical valves
• Antibody and synthetic molecular recognition
  materials

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My BIOI-MEMS onto Medical Application (II)

• Capabilities
• Rapid prototyping using Micromilling, Laser
  Ablation
• Metal Mold Fabrication (gt1000 replicates)
• Emboss/Injection mold in a variety of materials
  (ceramics, metal alloys, plastics)
• HARMS (Aspect ratios . 501)
• Pattern sub-micron features
• Fabricate 3D structures