On-chip flow cytometer using integrated photonics for the detection of human leukocytes.

Differentiation between leukocyte subtypes like monocytes and lymphocytes is essential for cell therapy and research applications. To guarantee the cost-effective delivery of functional cells in cell therapies, billions of cells must be processed in a limited time. Yet, the sorting rates of commercial cell sorters are not high enough to reach the required yield. Process parallelization by using multiple instruments increases variability and production cost. A compact solution with higher throughput can be provided by multichannel flow cytometers combining fluidics and optics on-chip. In this work, we present a micro-flow cytometer with monolithically integrated photonics and fluidics and demonstrate that both the illumination of cells, as well as the collection of scattered light, can be realized using photonic integrated circuits. Our device is the first with sufficient resolution for the discrimination of lymphocytes and monocytes. Innovations in microfabrication have enabled complete integration of miniaturized photonic components and fluidics in a CMOS-compatible wafer stack. In combination with external optics, the device is ready for the collection of fluorescence using the on-chip excitation.

An integrated multi-electrode-optrode array for in vitro optogenetics.

Modulation of a group of cells or tissue needs to be very precise in order to exercise effective control over the cell population under investigation. Optogenetic tools have already demonstrated to be of great value in the study of neuronal circuits and in neuromodulation. Ideally, they should permit very accurate resolution, preferably down to the single cell level. Further, to address a spatially distributed sample, independently addressable multiple optical outputs should be present. In current techniques, at least one of these requirements is not fulfilled. In addition to this, it is interesting to directly monitor feedback of the modulation by electrical registration of the activity of the stimulated cells. Here, we present the fabrication and characterization of a fully integrated silicon-based multi-electrode-optrode array (MEOA) for in vitro optogenetics. We demonstrate that this device allows for artifact-free electrical recording. Moreover, the MEOA was used to reliably elicit spiking activity from ChR2-transduced neurons. Thanks to the single cell resolution stimulation capability, we could determine spatial and temporal activation patterns and spike latencies of the neuronal network. This integrated approach to multi-site combined optical stimulation and electrical recording significantly advances today's tool set for neuroscientists in their search to unravel neuronal network dynamics.