Microfluidics promises a bright future for cell-based assays

Traditionally, high throughput assays have been conducted by collecting the average response from large populations of cells. While robotic operation can reduce sample handling errors there is still considerable room for errors to creep into studies when using small volumes in microtiter studies. This has led to interest in the development of microtiter devices that include microfluidic systems to provide better liquid delivery precision and increased washing efficiency; however, very few studies have been conducted to evaluate such on-chip assays. A team of researchers from the University of Glasgow, University of Hull and GlaxoSmithKline (GSK) have now published results in an early view article in the journal Analytical Chemistry​​ that show that microfluidic devices can provide fast reliable screening data using smaller sample volumes. In addition, they note that these systems have the potential to control and reveal sub-cellular events. According to the authors, ligand-gated ion channels represent around 40 per cent of the targets for drug discovery and many of these are modulated by calcium ions (Ca²⁺​). Measuring changes in the Ca²⁺​ flux has therefore become on of the preferred ways to measure the activity of new drug candidates. In order to quantitatively compare new microfluidic formats with established microtiter plate procedures the researchers compared the ability of the G-coupled protein receptor agonist, uridine 5'-triphosphate (UTP), to release Ca²⁺​ in the different systems. The researchers compared the traditional microtiter well-plate assays with microfluidic chip assays using both suspended and adherent cells that were cultured on-chip. They found that it was possible to show a close correlation between the suspended CHO (Chinese hamster ovary) cell dose-response for the UTP agonist on-chip and that achieved in a traditional microtiter plate. In addition, the use of adherent cells in the microfluidic device reduced the effects of hydrodynamic flow rates and enabled faster and more reliable screening data compared to that gained using the microtiter plates. The microfluidic system also demonstrated its potential to reveal sub-cellular events when the fluorescence signals generated by cells on the addition of UTP were monitored using a Carl Zeiss confocal microscope (Zeiss LSM 510). Four distinct fluorescence peaks were observed when individual cells were exposed to UTP, indicating a succession of Ca²⁺​ waves within the cell. This observation suggests that such measurements may provide a tool for studying the mechanism of signal trafficking and cell pathology. Because microfluidics devices enable precise and multiple liquid deliveries over cells new assays that involve sequential or dynamic cellular microenvironment changes can potentially be developed. "In future, the integration of other microfluidic subunits (such as valves and diluters) or sensors (electrochemical or optical) on-chip may further improve sample handling and analysis leading to an integrated high-throughput and high-content cell screen,"​ conclude the authors.