Microfluidics in cell-to-cell signalling measurements
Hormones are secreted molecules that carry biological information between cells. This type of cell-to-cell communication is vital to human life, and its dysregulation often underlies disease. In fact, the largest known class of cell surface receptors involved in hormone communication, G-protein coupled receptors, are also the largest class of known drug targets. Understanding these communication processes and their dysregulation requires an ability to ‘listen in’ on hormone communications with high fidelity.
To do this, highly sensitive and specific measurements of often challenging-to-detect chemical species – for example, peptides and proteins – must be made from within complex matrices such as biological fluids and tissues. This challenge has given rise to sophisticated analytical techniques for in vivo hormone measurements, including implanted microelectrodes for in situ detection of electrochemically active hormones from model organisms, and microdialysis for in situ sampling of electrically inactive molecules for ex vivo measurements.
Taking measurements from the tissues of living model organisms imparts broad biological and behavioural context to the measurements, but the inherent complexity and diversity of biological systems can obscure the underlying regulatory mechanisms of cellular communications. An alternative approach is the in vitro measurement of cellular secretions in a chemically and physically well-controlled environment. The emerging field of organ-on-a-chip research aims to develop organ-mimetic cell culture systems within microfluidic devices, where exquisite control of the solution environment and the delivery of nutrients and chemical stimuli is possible via precise laminar perfusion systems.
In addition to improved organ-mimetic cell culture conditions, microfluidic systems can offer analytical advantages over measurement platforms of larger volumes. Analysing cellular secretions within small volumes improves the mass limits of detection that can be achieved by conventional assays. For example, fluorescence assays may offer ca. 1nM concentration limits of detection, which corresponds to measuring 6 × 1010 molecules in a 100μL well of a microtiter plate, but only 6 × 105 molecules within a 1nL microfluidic volume. Improved mass limits of detection and reduced dilution of cellular secretions in microfluidic systems can be leveraged to improve the temporal resolution of secretion measurements, thereby capturing time course profiles of secretion dynamics. Rapid measurements in microfluidic devices are complemented by physical phenomena at the micro-scale, such as enhanced mass transfer effects and the availability of electroosmotic fluid manipulations, which offer additional analytical advantages and the potential for automation of complex analyses…