Microelectromechanical systems (MEMS) biochips represent a transformative technology in lab-on-a-chip systems, enabling precise manipulation and analysis of biological samples at microscale dimensions. These devices integrate fluidic, mechanical, and electronic components to perform complex biochemical assays, including DNA analysis, cell sorting, and point-of-care diagnostics. Their miniaturization, automation, and high-throughput capabilities make them indispensable in modern biomedical research and clinical applications.

Fabrication of MEMS biochips relies on advanced micromachining techniques. Polydimethylsiloxane (PDMS) molding is a widely used method due to its flexibility, optical transparency, and biocompatibility. PDMS is cast onto silicon masters patterned with photolithography, creating microchannels with feature sizes as small as 10 micrometers. Glass-silicon bonding is another critical process, where anodic or fusion bonding ensures leak-free sealing of microfluidic channels. Silicon substrates provide mechanical stability and compatibility with integrated electronics, while glass allows optical access for detection.

Fluidic control in MEMS biochips is achieved through microscale actuators such as microvalves and micropumps. Pneumatically actuated PDMS valves, for example, can switch fluid flow at frequencies exceeding 100 Hz, enabling precise routing of samples and reagents. Electrokinetic pumps leverage applied electric fields to move fluids via electroosmosis or electrophoresis, achieving flow rates in the nanoliter to microliter per minute range. These components are essential for automating multi-step assays, such as polymerase chain reaction (PCR) for DNA amplification or immunoassays for protein detection.

DNA analysis on MEMS biochips often involves integrated PCR chambers and capillary electrophoresis (CE) channels. Silicon-based heaters and temperature sensors enable rapid thermal cycling, with heating rates exceeding 10°C per second due to the low thermal mass of microfabricated structures. CE separation in glass microchannels achieves high resolution, resolving DNA fragments differing by as little as 10 base pairs. Detection is typically performed via laser-induced fluorescence, where photodiodes or CCD arrays capture emitted signals with high sensitivity.

Cell sorting applications leverage MEMS-based dielectrophoresis (DEP) or acoustophoresis. DEP electrodes generate non-uniform electric fields to separate cells based on their dielectric properties, achieving purities exceeding 90% for rare cell populations such as circulating tumor cells. Acoustophoresis uses surface acoustic waves (SAWs) to deflect cells into different outlets at throughputs of several thousand cells per second. These techniques are critical for liquid biopsy and stem cell isolation.

Point-of-care diagnostics benefit from the portability and automation of MEMS biochips. Electrochemical detection is commonly integrated for biomarker quantification, where screen-printed electrodes measure redox reactions with detection limits in the picomolar range. For example, glucose biosensors employ immobilized enzymes to generate amperometric signals proportional to analyte concentration. Optical detection methods, such as waveguide-based interferometry, provide label-free measurement of binding events in real time.

Challenges in MEMS biochip development include minimizing nonspecific adsorption and improving long-term stability. Surface modifications with polyethylene glycol (PEG) or zwitterionic polymers reduce fouling in microchannels. Encapsulation techniques protect sensitive components from environmental degradation, extending shelf life for commercial applications.

Future advancements may focus on monolithic integration of sensors and fluidic controls, reducing reliance on external instrumentation. Emerging materials like graphene-enhanced electrodes could improve sensitivity, while AI-driven fluidic algorithms may optimize assay protocols dynamically. The continued convergence of MEMS with nanotechnology and biotechnology will further expand the capabilities of these systems in precision medicine and global health.

In summary, MEMS biochips are a cornerstone of modern lab-on-a-chip technologies, offering unparalleled precision in biological analysis. Their fabrication, fluidic control mechanisms, and detection methodologies enable diverse applications from genomics to diagnostics, driving innovation in both research and clinical settings.