The 3DEP system
uses a patented chip design which is low cost, simple to use and allows the analysis of thousands of cells simultaneously.
Low cost disposable chips suitable for a large range of cell types from large myocytes to bacteria.
Applications include cancer diagnostics, monitoring apoptosis, stem-cell differentiation, drug discovery, in-vitro toxicology and many more.
- Membrane conductance describes the ability of a membrane to conduct charge, either through it or around it. It can be affected by the charges on the membrane surface, ion channel activity, and membrane morphology; the latter reason can be identified where there is a similar change in effective membrane capacitance, which is generally considered to be affected by membrane morphology almost exclusively. Multiplied by cell surface area, this gives the common whole-cell conductance parameter often used in cell electrophysiology.
- Effective membrane capacitance describes the ability of the membrane to store charge. Although in general the membrane composition changes little (and therefore the amount of charge a small patch of membrane can store remains approximately constant), the model assumes the surface is billiard-ball smooth and spherical. Deviation from this – such as when the cell surface is covered in blebs, microvilli or invaginations – means that there is actually more membrane than expected, meaning more charge is stored. This appears in the model as an elevated value of effective membrane capacitance per unit area of cell. Naturally, this makes the parameter a very good indicator of cell surface morphology; if a cell actually were perfectly spherical we would anticipate a capacitance per unit area of 8mFm-2, and a proportional increase indicates a similar proportional increase in area. Recent work has suggested that certain cell mechanisms altering the composition of the membrane (such as glycosylation) can have an effect without a morphology change, but the most common explanation is morphological. This has been a very effecting method of discriminating between cells – including observing changes in differentiating stem cells, or differences in cancerous vs. healthy cells. It is also useful for identifying morphology changes when interpreting changes in membrane conductance. As with conductance, multiplying by area gives the whole-cell capacitance commonly used in cell electrophysiology
- Intracellular conductivity is a measure of the ionic charge in the cytoplasm that can move freely and hence contribute to conduction. It is related to membrane potential; the cytoplasm conductivity is related to the sum of the positive and negative charges in the cell, whereas the membrane potential derives from the difference in numbers of positive and negative charge. As such it is a useful marker for change in ion concentrations, or ion channel activity. It is also a very useful marker for cell permeabilisation; when a cell membrane becomes permeable, the pores that appear allow connection between cell interior and exterior, causing a rapid drop in intracellular conductivity. It is also a useful marker for apoptosis, as one of the first events in the apoptotic cascade is ion efflux and water efflux, both of which can change the conductivity significantly (down in the former case, up in the latter). The actual change depends on the cell type and apoptosis-inducing agent, but the change is usually significant. If you divide 1 by the intracellular conductivity it gives the cytoplasm resistivity parameters commonly used in cell electrophysiology.
- Multiple populations. Sometimes a sample will contain a mixture of two or more cell types with radically different electrical characteristics. Where two or three such populations exist it is possible to model the two of them. For example, a common even in the study of apoptosis is the formation of apoptotic bodies, which typically appear as a second population with a radius of 0.5-1µm and a lower-than-normal intracellular conductivity. The ratio of the two populations is indicative of their relative concentration, although this is not a direct comparative measure (as the populations have different sizes and absorbances). We have successfully modelled up to three populations in the same sample, though this requires very high quality spectra, which can be obtained by averaging together many different spectra using the software provided. Where populations are very heterogeneous, such as in clinical samples taken from oral swabs, it is not possible to determine the properties of all of the populations; however, the 3DEP software can be used to discriminate between different samples on the basis of different dispersion characteristics. This technique has been used to classify clinical samples as cancerous or non-cancerous, where determination of the actual electrophysiological parameters is not required.