Regulation of cell volume was one of the earliest evolutionary demands for life and remains a universal measure of cell metabolism. Since conventional methods to measure cell volume, such as microscopy, are complex and time-consuming, cell volume has not been used as the basis for cell-based screening. We have developed a microfabricated chip that can measure the volume of small numbers of cells in real time with unprecedented resolution. The method is applicable to adherent or suspended populations of cells and membrane-bound organelles. Our prototype device can detect volume changes in a monolayer of tissue-cultured astrocytes responding to anisotonic stimuli of <1mOsm. We determined the sensitivity to antibiotics of different E. coli strains in <10 min at 24 degrees C. This time can be reduced at higher temperatures enabling on-site clinical testing of infectious agents. Using the chip to screen natural products, we found a peptide in spider venom that inhibits eukaryotic volume regulation at approximately 100pM. The prototype chip made in silicon is inexpensive, reusable, and runs on low-voltage electrical power. The technology can be readily transferred to large arrays in plastic.

In this paper, we present a microfluidic chip that is capable of measuring electrical conductance through gap junction channels in a 2-dimensional cell sheet. The chip utilizes a tri-stream laminar flow to create a non-conductive sucrose gap between the two conducting solutions so that electrical current can pass across the sucrose gap only through the cells. Using the chip, we tested the effect of a gap junction inhibitor, 2-APB, on the electrical coupling of connexin 43 (Cx43) gap junction channels in NRK-49F cells. We found that 2-APB reversibly blocks the conductivity in a dose-dependent manner. The tri-stream chip further allows us to simultaneously follow the conductance changes and dye diffusion in real time. We show that 2-APB affects both conductance and diffusion, supporting the interpretation that both sets of data reflect the same gap junction activity. The chip provides a generic platform to investigate gap junction properties and to screen drugs that may inhibit or potentiate gap junction transmission.