文摘
Current strategies for cell-based screening generally focuson the development of highly specific assays, whichrequire an understanding of the nature of the signalingmolecules and cellular pathways involved. In contrast,changes in temperature of cells provides a measure ofaltered cellular metabolism that is not stimulus specificand hence could have widespread applications in cell-based screening of receptor agonists and antagonists, aswell as in the assessment of toxicity of new lead compounds. Consequently, we have developed a micromachined nanocalorimetric biological sensor using a smallnumber of isolated living cells integrated within a subnanoliter format, which is capable of detecting 13 nW ofgenerated power from the cells, upon exposure to achemical or pharmaceutical stimulus. The sensor comprises a 10-junction gold and nickel thermopile, integrated on a silicon chip which was back-etched to span a800-nm-thick membrane of silicon nitride. The thin-filmmembrane, which supported the sensing junctions of thethermoelectric transducer, gave the system a temperatureresolution of 0.125 mK, a low heat capacity of 1.2 nJmK-1, and a rapid (unfiltered) response time of 12 ms.The application of the system in ultra-low-volume cell-based assays could provide a rapid endogenous screen.It offers important additional advantages over existingmethods in that it is generic in nature, it does not requirethe use of recombinant cell lines or of detailed assaydevelopment, and finally, it can enable the use of primarycell lines or tissue biopsies.
