We present the Medimate Multireader, the first point-of-care lab on a chip device that is based on capillary electrophoresis. It employs disposable pre-filled microfluidic chips with closed electrode reservoirs and a single sample opening. Several technological innovations allow operation with closed reservoirs, which is essential for reliable point-of-care operation. The chips are inserted into a hand-held analyzer. In the present application, the device is used to measure the lithium concentration in blood. Lithium is quantified by conductivity detection after separation from other blood ions. Measurements in patients show good accuracy and precision, and there is no difference between the results obtained by skilled and non-skilled operators. This point-of-care device shows great promise as a platform for the determination of ionic substances in diagnostics or environmental analysis.
We report current developments in biomimetic flow-sensors based on flow sensitive mechano-sensors of crickets. Crickets have one form of acoustic sensing evolved in the form of mechanoreceptive sensory hairs. These filiform hairs are highly perceptive to low-frequency sound with energy sensitivities close to thermal threshold. In this work we describe hair-sensors fabricated by a combination of sacrificial poly-silicon technology, to form silicon-nitride suspended membranes, and SU8 polymer processing for fabrication of hairs with diameters of about 50 µm and up to 1 mm length. The membranes have thin chromium electrodes on top forming variable capacitors with the substrate that allow for capacitive read-out. Previously these sensors have been shown to exhibit acoustic sensitivity. Like for the crickets, the MEMS hair-sensors are positioned on elongated structures, resembling the cercus of crickets. In this work we present optical measurements on acoustically and electrostatically excited hair-sensors. We present adaptive control of flowsensitivity and resonance frequency by electrostatic spring stiffness softening. Experimental data and simple analytical models derived from transduction theory are shown to exhibit good correspondence, both confirming theory and the applicability of the presented approach towards adaptation.
This paper reports on recent research creating a family of electrophoresis-based point of care devices for the determination of a wide range of ionic analytes in various sample matrices. These devices are based on a first version for the point-of-care measurement of Li(+), reported in 2010 by Floris et al. (Lab Chip 2010, 10, 1799-1806). With respect to this device, significant improvements in accuracy, precision, detection limit, and reliability have been obtained especially by the use of multiple injections of one sample on a single chip and integrated data analysis. Internal and external validation by clinical laboratories for the determination of analytes in real patients by a self-test is reported. For Li(+) in blood better precision than the standard clinical determination for Li(+) was achieved. For Na(+) in human urine the method was found to be within the clinical acceptability limits. In a veterinary application, Ca(2+) and Mg(2+) were determined in bovine blood by means of the same chip, but using a different platform. Finally, promising preliminary results are reported with the Medimate platform for the determination of creatinine in whole blood and quantification of both cations and anions through replicate measurements on the same sample with the same chip.
In this paper we report on the latest developments in biomimetic flow-sensors based on the flow sensitive mechanosensors of crickets. Crickets have one form of acoustic sensing evolved in the form of mechanoreceptive sensory hairs. These filiform hairs are highly perceptive to low-frequency sound with energy sensitivities close to thermal threshold. Arrays of artificial hair sensors have been fabricated using a surface micromachining technology to form suspended silicon nitride membranes and double-layer SU-8 processing to form 1 mm long hairs. Previously, we have shown that these hairs are sensitive to low-frequency sound, using a laser vibrometer setup to detect the movements of the nitride membranes. We have now realized readout electronics to detect the movements capacitively, using electrodes integrated on the membranes.
A point-of-care device for the determination of elevated creatinine levels in blood is reported. This device potentially offers a new and simple clinical regime for the determination of creatinine that will give huge time savings and removal of several steps of determination. The test employs a disposable prefilled microchip and the handheld Medimate Multireader®. By optimizing the analytical conditions it was found that the LOD of the proposed method was 87 μM creatinine, close to the normal human serum levels that are in the range of 60 to 100 μM. A statistical analysis of the residual shows a normal distribution, indicating the absence of systematic errors in the proposed method. The test can be used to distinguish patients with renal insufficiency (creatinine levels >100 μM) from healthy persons. Long-term monitoring could furthermore distinguish between acute renal failure and chronic kidney disease by the rate of creatinine concentration rise.
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