Abstract:
Live cell assays are an important part of drug discovery pipelines and personalized point-of-care diagnostics. In this context, Lab-on-a-Chip (LOC) devices are being widely considered as emerging technologies that can support massively parallel analysis at a single cell level. Reportedly they provide unique capabilities to monitor single-cell signalling dynamics, especially in rare subpopulations such as cancer cells or haematopoietic stem cells. Despite a large body of evidence on the fluorescence imaging, impendence and optical spectroscopies for characterisation of single living cells on a chip, however, no attempts have been so far made to interface microfabricated chip-based technologies with environmental scanning electron microscopy (ESEM). Here we for the first time describe the development of a non-invasive and simplified DEP chip that can be interfaced with ESEM imaging to provide analysis of non-adherent cells immobilised in the positive DEP (pDEP) fields. DEP microelectrode arrays were fabricated using thin films of chrome/gold deposited to a thickness of 500 Å/1500 Å on the glass substrate using electron beam evaporation process. Chip-based arrays were applied for ESEM analysis of DEP-immobilised human leukaemic cells. Most importantly non-adherent cells remain viable during processing and are well retained during imaging. Our innovative approach avoids extensive preparative procedures, is easy to perform for non-specialised personnel and thus prospectively amenable for automation.
