O. Frey

Multi-target electrochemical biosensing enabled by integrated CMOS electronics

An integrated electrochemical measurement system, based on CMOS technology, is presented, which allows the detection of several analytes in parallel (multi-analyte) and enables simultaneous monitoring at different locations (multi-site). The system comprises a 576-electrode CMOS sensor chip, an FPGA module for chip control and data processing, and the measurement laptop. The advantages of the highly versatile system are demonstrated by two applications. First, a label-free, hybridization-based DNA sensor is enabled by the possibility of large-scale integration in CMOS technology. Second, the detection of the neurotransmitter choline is presented by assembling the chip with biosensor microprobe arrays. The low noise level enables a limit of detection of, e.g., 0.3 µM choline. The fully integrated system is self-contained: it features cleaning, functionalization and measurement functions without the need for additional electrical equipment. With the power supplied by the laptop, the system is very suitable for on-site measurements.

Dynamic and static impedance spectroscopy for single particle characterization in microfluidic chips

A comparison of dynamic and static impedance spectroscopy (DIS and SIS) for single particle analysis is presented in this work. Individual particles are perfused into microchannels comprising microelectrodes, which are either used to perform dynamic measurements of impedance differences, or to make static measurement after a stable immobilization of single particles at narrow orifices. Experimental results with polystyrene (PS) beads demonstrate the important characteristics of the two methods: High throughput of DIS enabling measurements of large numbers of single particles in solution, and the multi-frequency capability of SIS enabling long-term recording of immobilized single particles. These distinct features of the two microfluidic methods offer high throughput and high sensitivity in a combined application for single-cell analysis in systems biology.

Real-time multi-analyte online monitoring of 3d cell cultures by integrated enzyme-based biosensors in hanging drop networks

We present the integration of enzyme-based lactate and glucose biosensors into hanging-drop networks. Hangingdrop networks are an ideal microfluidic platform for formation, cultivation, and continuous and long-term observation of 3D microtissues. The implementation of biosensors enables in-situ online monitoring of the effects of different culturing conditions and compound dosages on the microtissues. A hybrid approach including glass sensor modules embedded into a microfluidic polydimethylsiloxane (PDMS)-based chip facilitates system integration. The biosensors enable real-time recording of lactate production and glucose consumption of human colon carcinoma spheroids.

Multi-site monitoring of choline and glutamate using biosensor microprobe arrays in combination with CMOS circuitry

Biosensor microprobe arrays for the simultaneous in vivo detection of the neurotransmitters choline and L-glutamate are presented. Combined with a custom-developed CMOS chip, comprising 24 potentiostatic circuits, recordings can be performed at high signal-to-noise ratio in multiple areas of a rats brain in parallel. The functionalization to create selective enzyme electrodes is based on electrochemical deposition methods and can be obtained by using functions of a versatile CMOS circuitry chip. The result is a compact all-in-one system convenient for on-site measurement. Biosensors show good selectivity, sensitivities larger than 100 µA mM−1 cm−2, detection limits of less than 0.3 µM, and response times below 1 second.