Integration of Cell Culture and Microfabrication Technology

Abstract

Recent progress in cell culture and microfabrication technologies has contributed to the development of cell-based biosensors for the functional characterization and detection of drugs, pathogens, toxicants, and odorants. The cell-based biosensors are composed of two transducers, where the primary transducer is cellular and the secondary transducer is typically electrical. Advances in gene manipulation and cell culture techniques have contributed to the development of the cell as a transducer, while microfabrication techniques have been applied to the development of integrating the cell with the second transducer. Cellular patterning using microfabrication techniques is essential for cell-based biosensors, cell culture analogues, tissue engineering, and fundamental studies of cell biology. The photolithographic technique is highly developed and has been widely used for patterning cells. Recently, a set of alternative techniques, largely based on soft lithoghraphy, has been developed for biological applications. Those techniques include microcontact printing, microfluidic patterning using microchannels, and laminar flow patterning. A classical metallic stencil patterning method has been improved by employing a rubber-like stencil. These cellular micropatterning techniques have been usefully employed to understand questions in fundamental cell biology, especially cellular interactions with various materials and other cells. Using these micropatterning tecchniques and insights into the interaction of cellular biology with surfaces, a wide array of biosensors have been developed. In this manuscript examples of cell-based biosensors are described. Neurons have a great potential for use in a cell-based biosensor because they are electrically excitable cells, from which electrical signals are generated with the binding of detecting molecules. Consequently, the electrical signals generated in the cell can be determined in a noninvasive manner. A microphysiometer is a device to detect functional responses from cells by measuring the change of extracellular pH. The main application of the microphysiometer is the analysis of functional responses of cells upon receptor stimulation. Development of a microscale cell culture analogue system, an in vitro animal or human surrogate, is another promising area using cell culture and microfabrication technologies. Such devices are potentially very useful in the fields of toxicology and drug testing because they may increase the accuracy of in vitro predictions, simplify testing procedures, and reduce the cost of such tests, allowing many more tests to be done with a limited set of resources.

A novel and simple cell-based detection system with a collagen-encapsulated B-lymphocyte cell line as a biosensor for rapid detection of pathogens and toxins

“…Cell-based sensors are often preferred to other kinds of recognition system as living cells best mimic a physiological situation. 9,55 Due to the inherent advantages of CBBs in screening of 'active' (eg, live pathogenic bacteria) vs 'nonactive' (eg, heat killed pathogenic bacteria) biological entities, the application of this types of biosensors are increasing rapidly, specially in clinical and environmental diagnostics, food safety, biosecurity and in advanced pathological applications. 4,5,9,10,16 In our study, we have shown that a B-cell hybridoma, which normally grows in suspension, can be immobilized in collagen matrices.…”

Continuous perfusion microfluidic cell culture array for high-throughput cell-based assays

“…Furthermore, an inexpensive integrated laboratory-scale cell culture and analysis system has yet to be realized. Recently, microfabrication and microfluidic technologies have attracted a lot of attention in this area, with promising applications in cell-based biosensors and drug screening (Park and Shuler, 2003). Microfabrication techniques offer the advantages of increased fluid control, ability to address the cellular length scale, approximating the physiologic culture environment, improved culture efficiency, and batch fabrication of high-throughput arrays.…”

A microfluidic culture platform for CNS axonal injury, regeneration and transport

“…Several biological studies use microfluidic systems fabricated with poly(dimethylsiloxane) (PDMS) as a platform for miniature immunoassays, separation of proteins and DNA, sorting and manipulation of cells, and microscale bioreactors [15][16][17][18][19] . Development of microfabricated devices for neurons has generally been engineering-oriented, to develop retinal protheses 20 and to use neurons for biosensor applications 17,21 .…”