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Towards CMOS integrated microfluidics using dielectrophoretic immobilization
Dielectrophoresis (DEP) is a nondestructive and noninvasive method which is favorable for point-of-care medical diagnostic tests. This technique exhibits prominent relevance in a wide range of medical applications wherein the miniaturized platform for manipulation (immobilization, separation or rotation), and detection of biological particles (cells or molecules) can be conducted. DEP can be performed using advanced planar technologies, such as complementary metal-oxide-semiconductor (CMOS) through interdigitated capacitive biosensors. The dielectrophoretically immobilization of micron and submicron size particles using interdigitated electrode (IDE) arrays is studied by finite element simulations. The CMOS compatible IDEs have been placed into the silicon microfluidic channel. A rigorous study of the DEP force actuation, the IDE’s geometrical structure, and the fluid dynamics are crucial for enabling the complete platform for CMOS integrated microfluidics and detection of micron and submicron-sized particle ranges. The design of the IDEs is performed by robust finite element analyses to avoid time-consuming and costly fabrication processes. To analyze the preliminary microfluidic test vehicle, simulations were first performed with non-biological particles. To produce DEP force, an AC field in the range of 1 to 5 V (peak-to-peak) is applied to the IDE. The impact of the effective external and internal properties, such as actuating DEP frequency and voltage, fluid flow velocity, and IDE’s geometrical parameters are investigated. The IDE based system will be used to immobilize and sense particles simultaneously while flowing through the microfluidic channel. The sensed particles will be detected using the capacitive sensing feature of the biosensor. The sensing and detecting of the particles are not in the scope of this paper and will be described in details elsewhere. However, to provide a complete overview of this system, the working principles of the sensor, the readout detection circuit, and the integration process of the silicon microfluidic channel are briefly discussed. © 2019 by the authors.
Micro-Electromechanical Affinity Sensor for the Monitoring of Glucose in Bioprocess Media
An affinity-viscometry-based micro-sensor probe for continuous glucose monitoring was investigated with respect to its suitability for bioprocesses. The sensor operates with glucose and dextran competing as binding partner for concanavalin A, while the viscosity of the assay scales with glucose concentration. Changes in viscosity are determined with a micro-electromechanical system (MEMS) in the measurement cavity of the sensor probe. The study aimed to elucidate the interactions between the assay and a typical phosphate buffered bacterial cultivation medium. It turned out that contact with the medium resulted in a significant long-lasting drift of the assay’s viscosity at zero glucose concentration. Adding glucose to the medium lowers the drift by a factor of eight. The cglc values measured off-line with the glucose sensor for monitoring of a bacterial cultivation were similar to the measurements with an enzymatic assay with a difference of less than ±0.15 g·L−1. We propose that lectin agglomeration, the electro-viscous effect, and constitutional changes of concanavalin A due to exchanges of the incorporated metal ions may account for the observed viscosity increase. The study has demonstrated the potential of the MEMS sensor to determine sensitive viscosity changes within very small sample volumes, which could be of interest for various biotechnological applications.
A Review on Passive and Integrated Near-Field Microwave Biosensors
In this paper we review the advancement of passive and integrated microwave biosensors. The interaction of microwave with biological material is discussed in this paper. Passive microwave biosensors are microwave structures, which are fabricated on a substrate and are used for sensing biological materials. On the other hand, integrated biosensors are microwave structures fabricated in standard semiconductor technology platform (CMOS or BiCMOS). The CMOS or BiCMOS sensor technology offers a more compact sensing approach which has the potential in the future for point of care testing systems. Various applications of the passive and the integrated sensors have been discussed in this review paper.
Graphene Schottky Junction on Pillar Patterned Silicon Substrate
A graphene/silicon junction with rectifying behaviour and remarkable photo-response was fabricated by transferring a graphene monolayer on a pillar-patterned Si substrate. The device forms a 0.11 eV Schottky barrier with 2.6 ideality factor at room temperature and exhibits strongly biasand temperature-dependent reverse current. Below room temperature, the reverse current grows exponentially with the applied voltage because the pillar-enhanced electric field lowers the Schottky barrier. Conversely, at higher temperatures, the charge carrier thermal generation is dominant and the reverse current becomes weakly bias-dependent. A quasi-saturated reverse current is similarly observed at room temperature when the charge carriers are photogenerated under light exposure. The device shows photovoltaic effect with 0.7% power conversion efficiency and achieves 88 A/W photoresponsivity when used as photodetector. © 2019 by the authors.
Design and Fabrication of a BiCMOS Dielectric Sensor for Viscosity Measurements: A Possible Solution for Early Detection of COPD
The viscosity variation of sputum is a common symptom of the progression of Chronic Obstructive Pulmonary Disease (COPD). Since the hydration of the sputum defines its viscosity level, dielectric sensors could be used for the characterization of sputum samples collected from patients for early diagnosis of COPD. In this work, a CMOS-based dielectric sensor for the real-time monitoring of sputum viscosity was designed and fabricated. A proper packaging for the ESD-protection and short-circuit prevention of the sensor was developed. The performance evaluation results show that the radio frequency sensor is capable of measuring dielectric constant of biofluids with an accuracy of 4.17%. Integration of this sensor into a portable system will result in a hand-held device capable of measuring viscosity of sputum samples of COPD-patients for diagnostic purposes.
Prolonged Corrosion Stability of a Microchip Sensor Implant during In Vivo Exposure
A microelectronic biosensor was subjected to in vivo exposure by implanting it in the vicinity of m. trapezii (Trapezius muscle) from cattle. The implant is intended for the continuous monitoring of glucose levels, and the study aimed at evaluating the biostability of exposed semiconductor surfaces. The sensor chip was a microelectromechanical system (MEMS) prepared using 0.25 µm complementary metal–oxide–semiconductor CMOS/BiCMOS technology. Sensing is based on the principle of affinity viscometry with a sensoric assay, which is separated by a semipermeable membrane from the tissue. Outer dimensions of the otherwise hermetically sealed biosensor system were 39 × 49 × 16 mm. The test system was implanted into cattle in a subcutaneous position without running it. After 17 months, the device was explanted and analyzed by comparing it with unexposed chips and systems. Investigations focused on the MEMS chip using SEM, TEM, and elemental analysis by EDX mapping. The sensor chip turned out to be uncorroded and no diminishing of the topmost passivation layer could be determined, which contrasts remarkably with previous results on CMOS biosensors. The negligible corrosive attack is understood to be a side effect of the semipermeable membrane separating the assay from the tissue. It is concluded that the separation has enabled a prolonged biostability of the chip, which will be of relevance for biosensor implants in general.