Time-of-flight thermal flowrate sensor for lab-on-chip applications.

We describe a thermal microflowrate sensor for measuring liquid flow velocity in microfluidic channels, which is capable of providing a highly accurate response independent of the thermal and physical properties of the working liquid. The sensor consists of a rectangular channel containing a heater and several temperature detectors microfabricated on suspended silicon bridges. Heat pulses created by the heater are advected downstream by the flow and are detected using the temperature detector bridges. By injecting a pseudo-stochastic thermal signal at the heater and performing a cross correlation between the detected and the injected signals, we can measure the single-pulse response of the system with excellent signal-to-noise ratio and hence deduce the thermal signal time-of-flight from heater to detector. Combining results from several detector bridges allows us to eliminate diffusion effects, and thus calculate the flow velocity with excellent accuracy and linearity over more than two orders of magnitude. The experimental results obtained with several test fluids closely agree with data from finite element analysis. We developed a phenomenological model which supports and explains the observed sensor response. Several fully functional sensor prototypes were built and characterized, proving the feasibility and providing a critical component to microfluidic lab-on-chip applications where accurate flow measurements are of importance.

BioMEA: a versatile high-density 3D microelectrode array system using integrated electronics.

Microelectrode arrays (MEAs) offer a powerful tool to both record activity and deliver electrical microstimulations to neural networks either in vitro or in vivo. Microelectronics microfabrication technologies now allow building high-density MEAs containing several hundreds of microelectrodes. However, dense arrays of 3D micro-needle electrodes, providing closer contact with the neural tissue than planar electrodes, are not achievable using conventional isotropic etching processes. Moreover, increasing the number of electrodes using conventional electronics is difficult to achieve into compact devices addressing all channels independently for simultaneous recording and stimulation. Here, we present a full modular and versatile 256-channel MEA system based on integrated electronics. First, transparent high-density arrays of 3D-shaped microelectrodes were realized by deep reactive ion etching techniques of a silicon substrate reported on glass. This approach allowed achieving high electrode aspect ratios, and different shapes of tip electrodes. Next, we developed a dedicated analog 64-channel Application Specific Integrated Circuit (ASIC) including one amplification stage and one current generator per channel, and analog output multiplexing. A full modular system, called BIOMEA, has been designed, allowing connecting different types of MEAs (64, 128, or 256 electrodes) to different numbers of ASICs for simultaneous recording and/or stimulation on all channels. Finally, this system has been validated experimentally by recording and electrically eliciting low-amplitude spontaneous rhythmic activity (both LFPs and spikes) in the developing mouse CNS. The availability of high-density MEA systems with integrated electronics will offer new possibilities for both in vitro and in vivo studies of large neural networks.