A Transparent Semiconducting Surface for Capturing and Releasing Single Cells from a Complex Cell Mixture

Abstract

Selective isolation of individual target cells from a heterogeneous population is technically challenging; however, the ability to retrieve single cells can have high significance in various aspects of biological research. Here, we present a new photoelectrochemical surface based on a transparent electrode that is compatible with high-resolution fluorescence microscopy for isolating individual rare cells from complex biological samples. This is underpinned by two important factors: (i) careful design of the electrode by patterning discrete Au disks of micron dimension on amorphous silicon–indium tin oxide films and (ii) orthogonal surface chemistry, which modifies the patterned electrode with self-assembly layers of different functionalities, to selectively capture target cells on the Au disks and resist cell binding to the amorphous silicon surface. The co-stimulation of the surface using light from a microscope and an electric potential triggers the reductive desorption of the alkanethiol monolayer from the Au disks to release the single cells of interest from the illuminated regions only. Using circulating tumor cells as a model, we demonstrate the capture of cancer cells on an antibody-coated surface and selective release of single cancer cells with low expression of epithelial cell adhesion molecules.

Near-IR Photoinduced Electrochemiluminescence Imaging with Structured Silicon Photoanodes

“…As such, these results present the first example of near-IR PECL imaging. In addition, our approach provides a general solution for light-addressable electrochemistry on Si, which is complementary to the use of an a-Si overlayer, − (note that a-Si has been reported inefficient in the specific case of PECL) . In these proof-of-principle experiments, we measured a resolution of 60 μm, a factor of 3 above the value expected from transport simulations, indicating room for improvements, most likely in the optimization of the carrier transfer rates to the electrolyte.…”

“…In this frame, a-Si has been employed as a substrate for the lightaddressable electrodeposition of Pt, 9 NiMo, 9 and Cu 2 O nanoparticles 10 and, more recently, for the light-addressable release of single cells. 11 Electrochemiluminescence (ECL) is the generation of light induced by an electrochemical reaction. It generally produces the excited state of a luminophore at an electrode surface, leading to the emission of visible photons.…”

“…In a recent work, amorphous Si (a-Si) has been proven an efficient material for light-addressable electrochemistry because of its reduced carrier diffusion length ( L D ) compared to crystalline Si. In this frame, a-Si has been employed as a substrate for the light-addressable electrodeposition of Pt, NiMo, and Cu 2 O nanoparticles and, more recently, for the light-addressable release of single cells …”

Label-Free Imaging of Cell Apoptosis by a Light-Addressable Electrochemical Sensor

“…Due to the unique light addressability, the LAES has been extensively developed for multiplexed detection and bio­(chemical) imaging. For instance, LAES has been applied successfully to single-cell measurement and manipulation by focusing a laser beam to the size of a single cell. − We have previously reported an AC photocurrent measurement at electrolyte–semiconductor (ES) interfaces showing a high signal-to-noise ratio (SNR), which enables in situ photoelectrochemical imaging of surface charge of isolated living cells by addressing a two-dimensional (2D) array of measurement sites. , …”