Cell culture samples consisting of multiple cells provide only an average response rate to manipulation. Whole cell populations thereby miss unique responses of cell subpopulations. Scientists could benefit from the ability to study each cell individually and observe real-time responses to a drug or an experimental condition. Analytical technology used in cell-based assays has progressed to the point where cell populations can be observed at single-cell resolution. Advanced high-content analysis (HCA) techniques enable individual and sequential cell measurements, but they require expensive instrumentation and can be used only with adherent cells.
To overcome these limitations, the first slide-based HCA tool to facilitate the study of individual, living, adhering, and nonadhering cells within a cell population was developed. In addition, real-time data collection may be conducted on individual cells throughout the process of interventions, such as exposure to drugs or altered experimental conditions.
The NUNC (www.nuncbrand.com) LiveCell Array microscope slide contains a compact array of picowells that are available in four sizes. The 15-micron and 20-micron diameter wells accommodate individual cells, such as cell lines, primary blood cells, primary bone marrow cells, and beta cells. The 100-micron and 250-micron diameter wells accommodate large cells or groups of smaller cells. Common cells for these larger picowells include plant cells, neuronal cells, cell clusters, including islets of langerhans and neurospheres, and tissue-like cell aggregates.
The array and its sliding cover slip (Figure 1) are made of glass and embedded in a plastic slide frame. Cells are applied to the array and covered with the sliding cover slip. Wash solutions, dyes, and treatments are applied to a raised area at the edge of the cover slip, and fluid is drawn by capillary action over the cells.
The LiveCell Array can be used with any standard upright or inverted microscope and allows scientists to easily perform HCA using a minimal number of cells and costly reagents. In addition, it offers the researchers the ability to:
• perform long-term, nonintrusive, and repeated measurements on intact, living, adherent, or nonadherent cells;
• study heterogeneous cell populations to observe individual responses to treatment and rare events;
• perform multiple functional assays on living cells followed by postfixation studies on the same cells, as well as correlate between data sets (e.g., intracellular immunoassaying);
• perform kinetic measurements of nonsynchronous activities in individual cells observing each cell;
• perform measurements on a cellular-to-molecular level, correlating whole cell measurements with molecular events; and
• analyze and compare actual measurements of subpopulations and individual cells, rather than use mean values of entire populations.