Gold-induced photothermal background in on-chip surface enhanced stimulated Raman spectroscopy.

Surface enhanced Raman spectroscopy (SERS) and stimulated Raman spectroscopy (SRS) are well established techniques capable of boosting the strength of Raman scattering. The combination of both techniques (surface enhanced stimulated Raman spectroscopy, or SE-SRS) has been reported using plasmonic nanoparticles. In parallel, waveguide enhanced Raman spectroscopy has been developed using nanophotonic and nanoplasmonic waveguides. Here, we explore SE-SRS in nanoplasmonic waveguides. We demonstrate that a combined photothermal and thermo-optic effect in the gold material induces a strong background signal that limits the detection limit for the analyte. The experimental results are in line with theoretical estimates. We propose several methods to reduce or counteract this background.

Ultra-sensitive slot-waveguide-enhanced Raman spectroscopy for aqueous solutions of non-polar compounds using a functionalized silicon nitride photonic integrated circuit.

We demonstrate an ultra-sensitive waveguide-enhanced Raman sensor for low concentration organic compounds dissolved in water. The spectra are obtained using silicon nitride slot waveguides coated with a thin film of hexamethyldisilazane-modified mesoporous silica. Enriched locally by 600-fold within the coating, a micromolar level of cyclohexanone is probed. The sensor is also capable of simultaneous quantification of multiple analytes, and the adsorbed analytes can be completely released from the coating. These properties make this on-chip Raman sensor promising for diverse applications, especially for the monitoring of non-polar organics and biomolecules in aqueous environments.

Open-cell recording of action potentials using active electrode arrays.

The investigation of complex communication in cellular networks requires superior measurement tools than those available to date. Electrode arrays integrated onto silicon electronics are increasingly used to measure the electrical activity of cells in an automated and highly parallelized fashion, but they are restricted to recording extracellular potentials. Here, we report on an array of TiN electrodes built using standard silicon electronics for intracellular action potential recording. Intracellular access, possible at each of the 16 384 electrodes on the chip, was accomplished by local membrane electroporation using electrical stimulation with subcellular, micrometer-sized electrodes. Access to the cell interior was transient and could be tuned in duration by adapting the electroporation protocol. Intracellular sensing was found to be minimally invasive in the short and long-term, allowing consecutive intracellular recordings from the same cell over the course of days. Finally, we applied this method to investigate the effect of an ion channel blocker on cardiac electrical activity. This technique opens the door to massively parallel, long-term intracellular recording for fundamental electrophysiology and drug screening.

Single-cell recording and stimulation with a 16k micro-nail electrode array integrated on a 0.18 µm CMOS chip.

To cope with the growing needs in research towards the understanding of cellular function and network dynamics, advanced micro-electrode arrays (MEAs) based on integrated complementary metal oxide semiconductor (CMOS) circuits have been increasingly reported. Although such arrays contain a large number of sensors for recording and/or stimulation, the size of the electrodes on these chips are often larger than a typical mammalian cell. Therefore, true single-cell recording and stimulation remains challenging. Single-cell resolution can be obtained by decreasing the size of the electrodes, which inherently increases the characteristic impedance and noise. Here, we present an array of 16,384 active sensors monolithically integrated on chip, realized in 0.18 µm CMOS technology for recording and stimulation of individual cells. Successful recording of electrical activity of cardiac cells with the chip, validated with intracellular whole-cell patch clamp recordings are presented, illustrating single-cell readout capability. Further, by applying a single-electrode stimulation protocol, we could pace individual cardiac cells, demonstrating single-cell addressability. This novel electrode array could help pave the way towards solving complex interactions of mammalian cellular networks.

Micro-sized syringes for single-cell fluidic access integrated on a micro-electrode array CMOS chip.

Very-large scale integration and micro-machining have enabled the development of novel platforms for advanced and automated examination of cells and tissues in vitro. In this paper, we present a CMOS chip designed in a commercial 0.18 µm technology with integrated micro-syringes combined with micro-nail shaped electrodes and readout electronics. The micro-syringes could be individually addressed by a through-wafer micro-fluidic channel with an inner diameter of 1 µm. We demonstrated the functionality of the micro-fluidic access by diffusion of fluorescent species through the channels. Further, hippocampal neurons were cultured on top of an array of micro-syringes, and focused ion beam-scanning electron microscopy cross-sections revealed protrusion of the cells inside the channels, creating a strong interface between the membrane and the chip surface. This principle demonstrates a first step towards a novel type of automated in vitro platforms, allowing local delivery of substances to cells or advanced planar patch clamping.