Bio-MEMS

A broad definition for bio-MEMS can be used to refer to the science and technology of operating at the microscale for biological and biomedical applications, which may or may not include any electronic or mechanical functions.

[3] Firstly, drug discovery in the last decades leading up to the 1990s had been limited due to the time and cost of running many chromatographic analyses in parallel on macroscopic equipment.

[3] Thirdly, DARPA of the US Department of Defense supported a series of microfluidic research programs in the 1990s after realizing there was a need to develop field-deployable microsystems for the detection of chemical and biological agents that were potential military and terrorist threats.

[10] Due to being single-use only, larger than their MEMS counterparts, and the requirement of clean room facilities, high material and processing costs make silicon-based bio-MEMS less economically attractive.

[3][15] Cell micropatterning can be done using microcontact patterning of extracellular matrix proteins, cellular electrophoresis, optical tweezer arrays, dielectrophoresis, and electrochemically active surfaces.

[18] Paper-based analytical devices are particularly attractive for point-of-care diagnostics in developing countries for both the low material cost and emphasis on colorimetric assays which allow medical professionals to easily interpret the results by eye.

[3] Paper-based replicas have demonstrated the same effectiveness in performing common microfluidic operations such as hydrodynamic focusing, size-based molecular extraction, micro-mixing, and dilution; the common 96- and 384-well microplates for automated liquid handling and analysis have been reproduced through photolithography on paper to achieve a slimmer profile and lower material cost while maintaining compatibility with conventional microplate readers.

[30] One common use for this technique is in detecting nucleotide mismatches in DNA because the variation in mass caused by the presence of an incorrect base is enough to change the resonant frequency of the cantilever and register a signal.

[33] The main methods for creating an oligonucleotide microarray are by gel pads (Motorola), microelectrodes (Nanogen), photolithography (Affymetrix), and inkjet technology (Agilent).

[3] Subsequently, cDNA molecules (each corresponding to one gene) are immobilized as ~100 μm diameter spots on a membrane, glass, or silicon chip by metallic pins.

[39] PCR chips serve to miniaturize the reaction environment to achieve rapid heat transfer and fast mixing due to the larger surface-to-volume ratio and short diffusion distances.

[3] The ability to perform medical diagnosis at the bedside or at the point-of-care is important in health care, especially in developing countries where access to centralized hospitals is limited and prohibitively expensive.

Other notable advancements include the creation of nano-Velcro surfaces by Hsian-Rong Tseng's team at UCLA, designed to enhance cell capture efficiency through nanostructured polymer fiber meshes (Tseng et al., 2012), and the development of sinusoidal channels by Steven A. Soper's group at UNC Chapel Hill, which improves cell capture via geometrical modifications (Soper et al., 2011).

Microfluidic cell cultures are potentially a vast improvement because they can be automated, as well as yield lower overall cost, higher throughput, and more quantitative descriptions of single-cell behaviour variability.

[3] In situ microscopy assays with microfluidic cell cultures may help in this regard, but have inherently lower throughput due to the microscope probe having only a small field of view.

[3] The Berkeley Lights Beacon platform has resolved the issue of collection and detection by performing microfluidic culture on an array of photoconductors which can be optoelectrically activated to manipulate cells across the chip.

[48] Similarly, integrating microfluidics with micropatterned co-cultures has enabled modelling of organs where multiple vascularized tissues interface, such as the blood–brain barrier and the lungs.

[3] Organ-level lung functions have been reconstituted on lung-on-a-chip devices where a porous membrane and the seeded epithelial cell layer are cyclically stretched by applied vacuum on adjacent microchannels to mimic inhalation.

[51] Developed solutions include the use of continuous axial oxygen gradients[53] and arrays of microfluidic cell culture chambers separated by thin PDMS membranes to gas-filled microchannels.

[54] Fluid shear stress is relevant in the stem cell differentiation of cardiovascular lineages as well as late embryogenesis and organogenesis such as left-right asymmetry during development.

[51] Macro-scale studies do not allow quantitative analysis of shear stress to differentiation because they are performed using parallel-plate flow chambers or rotating cone apparatuses in on-off scenarios only.

[57] Using ECM microarrays to optimize combinatorial effects of collagen, laminin, and fibronectin on stem cells is more advantageous than conventional well plates due to its higher throughput and lower requirement of expensive reagents.

[51] Embryoid bodies are a common in vitro pluripotency test for stem cells and their size needs to be controlled to induce directed differentiation to specific lineages.

[51] High throughput formation of uniform sized embryoid bodies with microwells and microfluidics allows easy retrieval and more importantly, scale up for clinical contexts.

[3] Microfluidics have been applied in these technologies to better mimic the in vivo microenvironment with patterned topographic and biochemical surfaces for controlled spatiotemporal cell adhesion, as well as minimization of dead volumes.

The goal of implantable microelectrodes is to interface with the body's nervous system for recording and sending bioelectrical signals to study disease, improve prostheses, and monitor clinical parameters.

[67] Extracellular microelectrodes have been patterned onto an inflatable helix-shaped plastic in cochlear implants to improve deeper insertion and better electrode-tissue contact for transduction of high-fidelity sounds.

[3][72] Incorporation of sensors onto surgical tools also allows tactile feedback for the surgeon, identification of tissue type via strain and density during cutting operations, and diagnostic catheterization to measure blood flows, pressures, temperatures, oxygen content, and chemical concentrations.

[73] Bio-MEMS technology using piezoelectric transducers to liquid reservoirs can be used in these circumstances to generate narrow size distribution of aerosols for better drug delivery.

[73] Implantable drug delivery systems have also been developed to administer therapeutic agents that have poor bioavailability or require localized release and exposure at a target site.