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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