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A miniature device enabling parallel in vivo detection of the neurotransmitter choline in multiple brain regions of freely behaving rodents is presented. This is achieved by combining a biosensor microprobe array with a custom-developed CMOS chip. Each silicon microprobe comprises multiple platinum electrodes that are coated with an enzymatic membrane and a permselective layer for selective detection of choline. The biosensors, based on the principle of amperometric detection, exhibit a sensitivity of 157±35 µA mM(-1) cm(-2), a limit of detection of below 1 µM, and a response time in the range of 1 s. With on-chip digitalization and multiplexing, parallel recordings can be performed at a high signal-to-noise ratio with minimal space requirements and with substantial reduction of external signal interference. The layout of the integrated circuitry allows for versatile configuration of the current range and can, therefore, also be used for functionalization of the electrodes before use. The result is a compact, highly integrated system, very convenient for on-site measurements.

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Clinical point of care testing often needs plasma instead of whole blood. As centrifugation is labor intensive and not always accessible, filtration is a more appropriate separation technique. The complexity of whole blood is such that there is still no commercially available filtration system capable of separating small sample volumes (10-100 µl) at the point of care. The microfluidics research in blood filtration is very active but to date nobody has validated a low cost device that simultaneously filtrates small samples of whole blood and reproducibly recovers clinically relevant biomarkers, and all this in a limited amount of time with undiluted raw samples. In this paper, we show first that plasma filtration from undiluted whole blood is feasible and reproducible in a low-cost microfluidic device. This novel microfluidic blood filtration element (BFE) extracts 12 µl of plasma from 100 µl of whole blood in less than 10 min. Then, we demonstrate that our device is valid for clinical studies by measuring the adsorption of interleukins through our system. This adsorption is reproducible for interleukins IL6, IL8, and IL10 but not for TNFα. Hence, our BFE is valid for clinical diagnostics with simple calibration prior to performing any measurement.

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The present work investigates the utilisation of the widely used SU-8 photoresist as an immobilisation matrix for glucose oxidase (GOx) for the development of glucose micro-biosensors. The strong advantage of the proposed approach is the simultaneous enzyme entrapment during the microfabrication process within a single step, which is of high importance for the simplification of the BioMEMS procedures. Successful encapsulation of the enzyme GOx in "customised" SU-8 microfabricated structures was achieved through optimisation of the one-step microfabrication process. Although the process involved contact with organic solvents, UV-light exposure, heating for pre- and post-bake and enzyme entrapment in a hard and rigid epoxy resin matrix, the enzyme retained its activity after encapsulation in SU-8. Measurements of the immobilised enzyme's activity inside the SU-8 matrix were carried out using amperometric detection of hydrogen peroxide in a 3-electrode setup. Films without enzyme showed negligible variation in current upon the addition of glucose, as opposed to films with encapsulated enzyme which showed a very clear increase in current. Experiments using films of increased thickness or enzyme concentration, showed a higher response, thus proving that the enzyme remained active not only on the film's surface, but also inside the matrix as well. The proposed enzyme immobilisation in SU-8 films opens up new possibilities for combining BioMEMS with biosensors and organic electronics.

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This article presents the design and fabrication of a microfluidic biosensor cartridge for the continuous and simultaneous measurement of biologically relevant analytes in a sample solution. The biosensor principle is based on the amperometric detection of hydrogen peroxide using enzyme-modified electrodes. The low-integrated and disposable cartridge is fabricated in PDMS and SU-8 by rapid prototyping. The device is designed in such a way that it addresses two major challenges of biosensors using microfluidics approaches. Firstly, the enzymatic membrane is deposited on top of the platinum electrodes via a microfluidic deposition channel from outside the cartridge. This decouples the membrane deposition from the cartridge fabrication and enables the user to decide when and with what mixture he wants to modify the electrode. Secondly, by using laminar sheath-flow of the sample and a buffer solution, a dynamic diffusion layer is created. The analyte has to diffuse through the buffer solution layer before it can reach the immobilized enzyme membrane on the electrode. Controlling of the thickness of the diffusion layer by variation of the flow-rate of the two layers enables the user to adjust the sensitivity and the linear region of the sensor. The point where the buffer and sample stream join proved critical in creating the laminar sheath-flow. Results of computational simulations considering fluid dynamics and diffusion are presented. The consistency of the device was investigated through detection of glucose and lactate and are in accordance with the CFD simulations. A sensitivity of 157+/-28 nA/mM for the glucose sensor and 79+/-12 nA/mM for the lactate sensor was obtained. The linear response range of these biosensors could be increased from initially 2 mM up to 15 mM with a limit of detection of 0.2 mM.

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The dynamics of formation of solute peaks in microfluidic systems are investigated by computer simulation. A finite-element numerical procedure is applied to analyze the diffusion- and flow-controlled concentration dispersion in a 40 microm-high rectangular flow-through channel. Two-dimensional concentration profiles are shown for channels with cross sections of large aspect ratio. The final shapes of the peaks are formed during a very short time period, ranging from a few milliseconds to about 1s for low and high flow velocities, respectively. The observed standard half-width sigma of the peaks is found to strictly follow a linear function of t(1/2) over the whole time range. The extrapolated long-term peak characteristics are in perfect agreement with theoretical predictions. For comparison, theoretical results on the concentration dispersion for solute peaks in open-channel liquid-chromatography (HPLC) are re-examined and applied.