Integrated Electrochemical and Optical Biosensing in Organs-on-Chip.

Demand for biocompatible, non-invasive, and continuous real-time monitoring of organs-on-chip has driven the development of a variety of novel sensors. However, highest accuracy and sensitivity can arguably be achieved by integrated biosensing, which enables in situ monitoring of the in vitro microenvironment and dynamic responses of tissues and miniature organs recapitulated in organs-on-chip. This paper reviews integrated electrical, electrochemical, and optical sensing methods within organ-on-chip devices and platforms. By affording precise detection of analytes and biochemical reactions, these methods expand and advance the monitoring capabilities and reproducibility of organ-on-chip technology. The integration of these sensing techniques allows a deeper understanding of organ functions, and paves the way for important applications such as drug testing, disease modeling, and personalized medicine. By consolidating recent advancements and highlighting challenges in the field, this review aims to foster further research and innovation in the integration of biosensing in organs-on-chip.

Scalable large-area mesh-structured microfluidic gradient generator for drug testing applications.

Microfluidic concentration gradient generators are useful in drug testing, drug screening, and other cellular applications to avoid manual errors, save time, and labor. However, expensive fabrication techniques make such devices prohibitively costly. Here, in the present work, we developed a microfluidic concentration gradient generator (µCGG) using a recently proposed non-conventional photolithography-less method. In this method, ceramic suspension fluid was shaped into a square mesh by controlling Saffman Taylor instability in a multiport lifted Hele-Shaw cell (MLHSC). Using the shaped ceramic structure as the template, µCGG was prepared by soft lithography. The concentration gradient was characterized and effect of the flow rates was studied using COMSOL simulations. The simulation result was further validated by creating a fluorescein dye (fluorescein isothiocanate) gradient in the fabricated µCGG. To demonstrate the use of this device for drug testing, we created various concentrations of an anticancer drug-curcumin-using the device and determined its inhibitory concentration on cervical cancer cell-line HeLa. We found that the IC50 of curcumin for HeLa matched well with the conventional multi-well drug testing method. This method of µCGG fabrication has multiple advantages over conventional photolithography such as: (i) the channel layout and inlet-outlet arrangements can be changed by simply wiping the ceramic fluid before it solidifies, (ii) it is cost effective, (iii) large area patterning is easily achievable, and (iv) the method is scalable. This technique can be utilized to achieve a broad range of concentration gradient to be used for various biological and non-biological applications.