Microfluidic: Unraveling the Potential of Microfabricateds A Game-Changer in Science and Technology
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Microfluidic |
History and Early
Developments
The field of microfluidic emerged in the 1980s and 1990s driven by advances in
materials science technologies like photolithography. During this early period,
scientists experimented with using photolithographic techniques borrowed from
the semiconductor industry to etch micro-scale channels into materials like
silicon, glass and polymers. One of the first published demonstrations of a microfabricated
device was by Stephen Jacobsen and colleagues at Stanford University in 1986.
They created an array of liquid-filled channels photolithographically etched
into a silicon substrate.
While the initial applications were focused on developing new tools for
chemical analysis and synthesizing nanoscale materials, researchers soon
realized the potential for microfabricateds to enable new classes of biomedical
diagnostic devices. A key reason for this is that Microfluidic allows
manipulating extremely tiny volumes of fluids - in the range of microliters
down to nanoliters or even picoliters. This gives scientists unprecedented
control over fluids at the micro-scale and opens up exciting possibilities in
areas like miniaturized biomedical assays.
Fabrication Methods
Many different fabrication techniques have been used over the years to etch
micro-scale channels and structures into substrate materials for microfabricated
devices. Besides photolithography which was employed in early work, some
commonly used techniques today include:
- Soft lithography: A set of techniques initially developed in the 1990s based
on using elastomeric stamps or molds made from materials like
polydimethylsiloxane (PDMS). PDMS is poured onto a patterned silicon master and
cured to create a replica with microscale features.
- Hot embossing lithography: Involves using a patterned metal or silicon stamp
coated with a releasing agent to press patterns into a polymer substrate like
PMMA held at elevated temperature.
- Laser ablation: Employing laser cutting or drilling to precisely etch away
material from polymer substrates to form microstructures and channels.
- X-ray lithography: An advanced photolithography technique that uses X-ray
exposure through a mask to pattern substrates with sub-micron resolution.
- 3D printing: Rapidly emerging additive manufacturing methods that can
directly 3D print entire microfabricated devices layer-by-layer, removing the
need for multiple fabrication steps.
Basic Design Principles
While fabrication techniques enable creating the actual physical structures,
the underlying designs of microfabricated chips have also evolved
significantly. Some key aspects of microfabricated device design include:
- Channel geometries and dimensions: Channels can have different cross-sections
like rectangular, semi-circular or triangular shapes etched to specific
micrometer-scale depths and widths optimized for a given application.
- Fluid routing structures: Networks of branching microchannels are
incorporated along with fluid routing components like inlets, outlets,
micromixers, valves etc. to precisely control fluid transport.
- Surface modification:Channel surfaces can be chemically or physically
modified to alter fluid wettability, control surface interactions and enable
different assay protocols.
- Integration of sensors: Electrochemical, optical or other microfabricated
sensors are directly embedded on-chip to allow real-time fluid or biomolecular
detection within microfabricated channels and networks.
- Portability and user interface: Designs have advanced to develop
self-contained, portable and easy-to-use microfluidic chips compatible with
minimal user handling and sample/reagent volumes.
Applications in Biomedicine and Biology
Given its ability to precisely manipulate and analyze extremely small volumes
of fluids and samples, microfabricateds has found numerous biomedical and
biological applications. Some key areas where microfabricated technologies have
made significant impact include:
- Point-of-care diagnostics: Portable microfabricated chips have been developed
for rapid testing of diseases in resource-limited settings without needing
centralized large laboratories. Examples include chips for HIV, malaria,
tuberculosis etc.
- Pathogen detection: Highly sensitive biosensors integrated on microfabricated
platforms allow detecting viruses or bacteria like E. coli without culturing.
Useful for food/water safety testing and biothreat detection.
- Genetic analysis: Microfabricated chips enable miniaturized DNA/RNA analysis
and sequencing via polymerase chain reaction (PCR), DNA electrophoresis and
other molecular biology techniques with far smaller sample/reagent volumes than
traditional benchtop methods.
- Cell analysis: Microfabricated devices have enabled new high-resolution
studies of single cells, multicellular spheroids, cell-cell interactions etc.
by culturing and imaging cells within enclosed on-chip microenvironments that
mimic tissues/organs.
- Tissue engineering: Microfabricated ‘organs-on-chips' precisely emulate human
tissue structures and physiological microenvironments to better model
organ/disease responses and expedite drug testing/development compared to
animal testing.
- Pathogen culture systems: Chips have automated complex culture systems to
continuously monitor bacterial or viral cultures in isolation without risks of
contamination compared to manual microbiology techniques.
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