Photothermal Detection of Individual Gold Nanoparticles: Perspectives for High‐Throughput Screening

We use photothermal microscopy to detect and image individual gold nanoparticles that are either embedded in a polymer film or immobilized in an aqueous environment. Reducing the numerical aperture of the detection optics allows us to achieve a 200-fold-enlarged detection volume while still retaining sufficient detectivity. We characterize the capabilities of this approach for the detection of gold colloids with a diameter of 20 nm, with emphasis on practical aspects that are important for high-throughput-screening applications. The extended detection volume in combination with the stability of the photothermal signal are major advantages compared to fluorescence-based approaches, which are limited by photoblinking and photobleaching. Careful consideration is given to the trade-off between the maximum increase in local temperature that can be tolerated by a biological specimen and the minimum integration time needed to reliably determine whether a given volume contains a target species. We find that our approach has the potential to increase the detection-limited flow rate (i.e. the limit given by the detection volume divided by the minimum detection time) by two to three orders of magnitude.