A photoelectrochemical platform for the capture and release of rare single cells

Abstract

For many normal and aberrant cell behaviours, it is important to understand the origin of cellular heterogeneity. Although powerful methods for studying cell heterogeneity have emerged, they are more suitable for common rather than rare cells. Exploring the heterogeneity of rare single cells is challenging because these rare cells must be first pre-concentrated and undergo analysis prior to classification and expansion. Here, a versatile capture & release platform consisting of an antibody-modified and electrochemically cleavable semiconducting silicon surface for release of individual cells of interest is presented. The captured cells can be interrogated microscopically and tested for drug responsiveness prior to release and recovery. The capture & release strategy was applied to identify rare tumour cells from whole blood, monitor the uptake of, and response to, doxorubicin and subsequently select cells for single-cell gene expression based on their response to the doxorubicin.

High‐Aspect‐Ratio Nanostructured Surfaces as Biological Metamaterials

“…While cell‐capture systems based on high‐aspect‐ratio nanostructures are relatively unexplored, the recent reports of combined capture–delivery systems, plus the advent of interesting photo‐active capture chemistries, suggest this is a growing area of research.…”

Light‐Addressable Ion Sensing for Real‐Time Monitoring of Extracellular Potassium

“…The missing link has been to obtain electrochemical information from single cells rather than thousands. Semiconducting surfaces offer the possibility to achieve single cell electrochemistry . After absorbing light of appropriate wavelength, a semiconductor generates electron–hole pairs and hence becomes conducting in that region.…”

“…A recent demonstration shows the successful application of the concept to a photoelectrochemical platform for the release of rare single cells. The platform showed the compatibility with microscopy imaging and enabled localizing the release of any desired single after comparing cell morphology, surface expression or drug responses …”

“…Redox molecules covalently bound to the oxide‐free silicon electrode are expected to offer a direct and amplified signal compared with traditional LAPS and may in principle be extended to the detection of multiple ions . Moreover, this ion sensing system may be compatible with other electrochemical approaches, such as cell–substrate impedance analysis, or integrated with the established single cell release platform, and hence would offer vast opportunities to study complex biological events.…”

Light‐Responsive Inorganic Biomaterials for Biomedical Applications

“…Moreover, the optical cell modulation by the single-cell assay also can provide cellular or intercellular-scale measurements to understand the functional diversity of the cells and identify phenotypically rare cells, rather than the overall result of treatment. [23] There are two main types of signals that were used to control cell behavior: electrochemical and temperature. The photothermal effects of inorganic nanomaterials and the ability to apply thermal stimulation on a single cell have been well established to understand the effect of small change of temperature influenced cellular function.…”