Enhancing signals of microfluidic impedance cytometry through optimization of microelectrode array.

Microfluidic impedance cytometry shows a great value in biomedical diagnosis. However, the crosstalk between neighboring microelectrodes strongly weakens the impedance signal. Hereby, we demonstrate a novel microfluidic impedance cytometer consisted of sensing electrodes and ground electrodes (GNDs). The simulation reveals a signal enhancement by more than five times with GNDs compared to that without ones. We also found that the linear correlation between the impedance at a high frequency and that at a low frequency varies as microparticle size changes, which can be used for microparticle classification. The study can help with microelectrode optimization and signal processing for microfluidic impedance analysis.

IoT PCR for pandemic disease detection and its spread monitoring.

During infectious disease outbreaks, the centers for disease control need to monitor particular areas. Considerable effort has been invested in the development of portable, user-friendly, and cost-effective systems for point-of-care (POC) diagnostics, which could also create an Internet of Things (IoT) for healthcare via a global network. However, at present IoT based on a functional POC instrument is not available. Here we show a fast, user-friendly, and affordable IoT system based on a miniaturized polymerase chain reaction device. We demonstrated the system's capability by amplification of complementary deoxyribonucleic acid (cDNA) of the dengue fever virus. The resulting data were then automatically uploaded via a Bluetooth interface to an Android-based smartphone and then wirelessly sent to a global network, instantly making the test results available anywhere in the world. The IoT system presented here could become an essential tool for healthcare centers to tackle infectious disease outbreaks identified either by DNA or ribonucleic acid.

LAMP-on-a-chip: Revising microfluidic platforms for loop-mediated DNA amplification.

Nucleic acid amplification for the detection of infectious diseases, food pathogens, or assessment of genetic disorders require a laboratory setting with specialized equipment and technical expertise. Isothermal deoxyribonucleic acid amplification methods, such as loop-mediated isothermal amplification (LAMP), exhibit characteristics ideal for point-of-care (POC) applications, since their instrumentation is simpler in comparison with the standard method of polymerase chain reaction. Other key advantages of LAMP are robustness and the production of pyrophosphate in the presence of the target gene, enabling to detect the reaction products using the naked eye. Polymerase inhibitors, presented in clinical samples, do not affect the amplification process, making LAMP suitable for a simple sample-to-answer diagnostic systems with simplified sample preparation. In this review, we discuss the trends in miniaturized LAMP techniques, such as microfluidic, paper-based, and digital with their advantages and disadvantages, especially for POC applications alongside our opinion of the future development of miniaturized LAMP.

Dry-contact microelectrode membranes for wireless detection of electrical phenotypes in neonatal mouse hearts.

Continuous monitoring of aberrant electrical rhythms during heart injury and repair requires prolonged data acquisition. We hereby developed a wearable microelectrode membrane that could be adherent to the chest of neonatal mice for in situ wireless recording of electrocardiogram (ECG) signals. The novel dry-contact membrane with a meshed parylene-C pad adjacent to the microelectrodes and the expandable meandrous strips allowed for varying size of the neonates. The performance was evaluated at the system level; specifically, the ECG signals (µV) acquired from the microelectrodes underwent two-stage amplification, band-pass filtering, and optical data transmission by an infrared Light Emitting Diode (LED) to the data-receiving unit. The circuitry was prototyped on a printed circuit board (PCB), consuming less than 300 µW, and was completely powered by an inductive coupling link. Distinct P waves, QRS complexes, and T waves of ECG signals were demonstrated from the non-pharmacologically sedated neonates at ~600 beats per minutes. Thus, we demonstrate the feasibility of both real-time and wireless monitoring cardiac rhythms in a neonatal mouse (17-20 mm and <1 g) via dry-contact microelectrode membrane; thus, providing a basis for diagnosing aberrant electrical conduction in animal models of cardiac injury and repair.

Dynamic Performance Comparison of Two Kalman Filters for Rate Signal Direct Modeling and Differencing Modeling for Combining a MEMS Gyroscope Array to Improve Accuracy.

In this paper, the performance of two Kalman filter (KF) schemes based on the direct estimated model and differencing estimated model for input rate signal was thoroughly analyzed and compared for combining measurements of a sensor array to improve the accuracy of microelectromechanical system (MEMS) gyroscopes. The principles for noise reduction were presented and KF algorithms were designed to obtain the optimal rate signal estimates. The input rate signal in the direct estimated KF model was modeled with a random walk process and treated as the estimated system state. In the differencing estimated KF model, a differencing operation was established between outputs of the gyroscope array, and then the optimal estimation of input rate signal was achieved by compensating for the estimations of bias drifts for the component gyroscopes. Finally, dynamic simulations and experiments with a six-gyroscope array were implemented to compare the dynamic performance of the two KF models. The 1σ error of the gyroscopes was reduced from 1.4558°/s to 0.1203°/s by the direct estimated KF model in a constant rate test and to 0.5974°/s by the differencing estimated KF model. The estimated rate signal filtered by both models could reflect the amplitude variation of the input signal in the swing rate test and displayed a reduction factor of about three for the 1σ noise. Results illustrate that the performance of the direct estimated KF model is much higher than that of the differencing estimated KF model, with a constant input signal or lower dynamic variation. A similarity in the two KFs' performance is observed if the input signal has a high dynamic variation.

A Microgripper with a Post-Assembly Self-Locking Mechanism.

In this work, we report a new design for an electrostatically actuated microgripper with a post-assembly self-locking mechanism. The microgripper arms are driven by rotary comb actuators, enabling the microgripper to grip objects of any size from 0 to 100 µm. The post-assembly mechanism is driven by elastic deformation energy and static electricity to produce self-locking and releasing actions. The mechanism enables the microgripper arms to grip for long periods without continuously applying the external driving signal, which significantly reduces the effects and damage to the gripped objects caused by these external driving signals. The microgripper was fabricated using a Silicon-On-Insulator (SOI) wafer with a 30 µm structural layer. Test results show that this gripper achieves a displacement of 100 µm with a driving voltage of 33 V, and a metal wire with a diameter of about 1.6 mil is successfully gripped to demonstrate the feasibility of this post-assembly self-locking mechanism.

A toroidal SAW gyroscope with focused IDTs for sensitivity enhancement.

A surface acoustic wave (SAW) gyroscope measures the rate of rotational angular velocity by exploiting a phenomenon known as the SAW gyroscope effect. Such a gyroscope is a great candidate for application in harsh environments because of the simplification of the suspension vibration mechanism necessary for traditional microelectromechanical system (MEMS) gyroscopes. Here, for the first time, we propose a novel toroidal standing-wave-mode SAW gyroscope using focused interdigitated transducers (FIDTs). Unlike traditional SAW gyroscopes that use linear IDTs to generate surface acoustic waves, which cause beam deflection and result in energy dissipation, this study uses FIDTs to concentrate the SAW energy based on structural features, resulting in better focusing performance and increased SAW amplitude. The experimental results reveal that the sensitivity of the structure is 1.51 µV/(°/s), and the bias instability is 0.77°/s, which are improved by an order of magnitude compared to those of a traditional SAW gyroscope. Thus, the FIDT component can enhance the performance of the SAW gyroscope, demonstrating its superiority for angular velocity measurements. This work provides new insights into improving the sensitivity and performance of SAW gyroscopes.

A microchip based Z-cell absorbance detector integrating micro-lenses and slits for portable liquid chromatography.

A miniaturized microchip-based absorbance detector was developed for portable high-performance liquid chromatography (HPLC) to test glycated hemoglobin (HbA1c). The microchip integrating a Z-shaped cell, two collimating micro-lenses and two ink-filled optical slits is small in size (30 mm × 15 mm × 7 mm). The Z-shaped cell has a cross-sectional size of 500 µm × 500 µm and a physical optical path length of 2 mm. Two collimating micro-lenses were inserted in empty grooves on both sides of the cell, one micro-lens for collimating the initial light and the other for focusing the transmitted light. Optical slits on each end of the cell were used to block the stray light. Therefore, this detector indicated a low stray light level (0.011 %) and noise level (2.5 × 10-4 AU). This detector was applied for the commercial HPLC system to detect HbA1c level, and showed a low limit of detection (0.5 µg/mL) and excellent repeatability (≤ 2.03 %). The sensitivity was enhanced by 3.4 times when the optical path length was increased from 0.5 mm to 2 mm and the stray light was blocked by optical slits. The miniaturized microchip-based absorbance detector developed shows a great potential for application in portable and compact HPLC.

Characterization of Sensitivity of Time Domain MEMS Accelerometer.

This paper characterizes the sensitivity of a time domain MEMS accelerometer. The sensitivity is defined by the increment in the measured time interval per gravitational acceleration. Two sensitivities exist, and they can be enhanced by decreasing the amplitude and frequency. The sensitivity with minor nonlinearity is chosen to evaluate the time domain sensor. The experimental results of the developed accelerometer demonstrate that the sensitivities span from -68.91 µs/g to -124.96 µs/g and the 1σ noises span from 8.59 mg to 6.2 mg (amplitude of 626 nm: -68.91 µs/g and 10.21 mg; amplitude of 455 nm: -94.51 µs/g and 7.76 mg; amplitude of 342 nm: -124.96 µs/g and 6.23 mg), which indicates the bigger the amplitude, the smaller the sensitivity and the bigger the 1σ noise. The adjustable sensitivity provides a theoretical foundation for range self-adaption, and all the results can be extended to other time domain inertial sensors, e.g., a gyroscope or an inclinometer.

Rapid detection of glycosylated hemoglobin levels by a microchip liquid chromatography system in gradient elution mode.

BACKGROUND: The determination of glycosylated hemoglobin (HbA1c) is crucial for diabetes diagnosis and can provide more substantial results than the simple measurement of glycemia. While there is a lack of simple methods for the determination of HbA1c using a point-of-care test (POCT) compared to glycemia measurement. In particular, high-performance liquid chromatography (HPLC) is considered the current gold standard for determining HbA1c levels. However, commercial HPLC systems usually have some sort of disadvantages such as bulky size, high-cost and need for qualified operators. Therefore, there is an urgent demand to develop a portable, and fast HbA1c detection system consuming fewer reagents. RESULTS: We present a novel microchip that integrates a micromixer, passive injector, packed column and detection cell. The integrated microchip, in which all the microstructures were formed in the CNC machining center through micro-milling, is small in size (30 mm × 70 mm × 10 mm), and can withstand 1600 psi of liquid pressure. The integrated design is beneficial to reduce the band broadening caused by dead volume. Based on the microchip, a microchip liquid chromatography (LC) system was built and applied to the analysis of HbA1c. The separation conditions of HbA1c in blood calibrator samples were optimized using the microchip LC system. Samples containing four levels of HbA1c were completely separated within 2 min in optimal gradient conditions, with an inaccuracy (<3.2 %), a coefficient of variation (c.v. < 2.1 %) and a correlation coefficient (R2 = 0.993), indicating excellent separation efficiency and reproducibility. SIGNIFICANCE: The POCT of HbA1c is critical for diabetes diagnosis. The microchip chromatography system was developed for HbA1c determination, which contains an integrated microchip and works under a gradient elution. It surpasses existing chip technology in terms of separation performance and detection speed, providing a competitive advantage for POCT of HbA1c. It is considered one important step for realizing efficient portable systems for timely and accurate diabetes diagnosis.

MIMU Optimal Redundant Structure and Signal Fusion Algorithm Based on a Non-Orthogonal MEMS Inertial Sensor Array.

A micro-inertial measurement unit (MIMU) is usually used to sense the angular rate and acceleration of the flight carrier. In this study, multiple MEMS gyroscopes were used to form a spatial non-orthogonal array to construct a redundant MIMU system, and an optimal Kalman filter (KF) algorithm was established by a steady-state KF gain to combine array signals to improve the MIMU's accuracy. The noise correlation was used to optimize the geometric layout of the non-orthogonal array and reveal the mechanisms of influence of correlation and geometric layout on MIMU's performance improvement. Additionally, two different conical configuration structures of a non-orthogonal array for 4,5,6,8-gyro were designed and analyzed. Finally, a redundant 4-MIMU system was designed to verify the proposed structure and KF algorithm. The results demonstrate that the input signal rate can be accurately estimated and that the gyro's error can also be effectively reduced through fusion of non-orthogonal array. The results for the 4-MIMU system illustrate that the gyro's ARW and RRW noise can be decreased by factors of about 3.5 and 2.5, respectively. In particular, the estimated errors (1σ) on the axes of Xb, Yb and Zb were 4.9, 4.6 and 2.9 times lower than that of the single gyroscope.

Virtual Coriolis-Force-Based Mode-Matching Micromachine-Optimized Tuning Fork Gyroscope without a Quadrature-Nulling Loop.

A VCF-based mode-matching micromachine-optimized tuning fork gyroscope is proposed to not only maximize the scale factor of the device, but also avoid use of an additional quadrature-nulling loop to prevent structure complexity, pick-up electrode occupation, and coupling with a mode-matching loop. In detail, a mode-matching, closed-loop system without a quadrature-nulling loop is established, and the corresponding convergence and matching error are quantitatively analyzed. The optimal straight beam of the gyro structure is then modeled to significantly reduce the quadrature coupling. The test results show that the frequency split is narrowed from 20 Hz to 0.014 Hz. The scale factor is improved 20.6 times and the bias instability (BI) is suppressed 3.28 times. The observed matching accuracy demonstrates that a mode matching system without a quadrature suppression loop is feasible and that the proposed device represents a competitive design for a mode-matching gyroscope.

Digital polymerase chain reaction duplexing method in a single fluorescence channel.

The digital polymerase chain reaction (dPCR) technique can quantify specific sequences of deoxyribonucleic acid using either a droplet-based or chip-based system. dPCR duplexing methods in a single fluorescence channel are typically based on the difference in fluorescence amplitude (F) between two targets. The different targets are distinguished from each other by the F-value variation using non-equal probe concentrations or different target lengths. In the present study, we propose a single fluorescence channel-based dPCR duplexing method that combines a specific probe and intercalating dye to increase the difference in F values between the two targets. We selected two sequences, one from chromosome 18 (Chr18) detected only by the intercalating dye EvaGreen and the other from chromosome 21 (Chr21) detected by a combination of a 6-carboxyfluorescein (FAM) probe and EvaGreen. We performed the dPCR protocol and imaged the dPCR chip at room temperature to verify the proposed duplexing method. The result revealed that the difference in F values between Chr18 and Chr21 increased from ≈5% to 20% when using the FAM probe for Chr21 compared with the detection of both amplicons using EvaGreen only. The added FAM probe enabled two-target discrimination using a single-color fluorescent channel. We further determined the difference in F values at different temperatures using artificial dPCR images. This proposed method represents a simple option for single fluorescence channel dPCR duplexing, making it suitable for simplified dPCR systems used for point-of-care applications.

Deep-Learning Enabled Active Biomimetic Multifunctional Hydrogel Electronic Skin.

There is huge demand for recreating human skin with the functions of epidermis and dermis for interactions with the physical world. Herein, a biomimetic, ultrasensitive, and multifunctional hydrogel-based electronic skin (BHES) was proposed. Its epidermis function was mimicked using poly(ethylene terephthalate) with nanoscale wrinkles, enabling accurate identification of materials through the capabilities to gain/lose electrons during contact electrification. Internal mechanoreceptor was mimicked by interdigital silver electrodes with stick-slip sensing capabilities to identify textures/roughness. The dermis function was mimicked by patterned microcone hydrogel, achieving pressure sensors with high sensitivity (17.32 mV/Pa), large pressure range (20-5000 Pa), low detection limit, and fast response (10 ms)/recovery time (17 ms). Assisted by deep learning, this BHES achieved high accuracy and minimized interference in identifying materials (95.00% for 10 materials) and textures (97.20% for four roughness cases). By integrating signal acquisition/processing circuits, a wearable drone control system was demonstrated with three-degree-of-freedom movement and enormous potentials for soft robots, self-powered human-machine interaction interfaces of digital twins.

Brainmask: an ultrasoft and moist micro-electrocorticography electrode for accurate positioning and long-lasting recordings.

Bacterial cellulose (BC), a natural biomaterial synthesized by bacteria, has a unique structure of a cellulose nanofiber-weaved three-dimensional reticulated network. BC films can be ultrasoft with sufficient mechanical strength, strong water absorption and moisture retention and have been widely used in facial masks. These films have the potential to be applied to implantable neural interfaces due to their conformality and moisture, which are two critical issues for traditional polymer or silicone electrodes. In this work, we propose a micro-electrocorticography (micro-ECoG) electrode named "Brainmask", which comprises a BC film as the substrate and separated multichannel parylene-C microelectrodes bonded on the top surface. Brainmask can not only guarantee the precise position of microelectrode sites attached to any nonplanar epidural surface but also improve the long-lasting signal quality during acute implantation with an exposed cranial window for at least one hour, as well as the in vivo recording validated for one week. This novel ultrasoft and moist device stands as a next-generation neural interface regardless of complex surface or time of duration.

Signal processing of MEMS gyroscope arrays to improve accuracy using a 1st order Markov for rate signal modeling.

This paper presents a signal processing technique to improve angular rate accuracy of the gyroscope by combining the outputs of an array of MEMS gyroscope. A mathematical model for the accuracy improvement was described and a Kalman filter (KF) was designed to obtain optimal rate estimates. Especially, the rate signal was modeled by a first-order Markov process instead of a random walk to improve overall performance. The accuracy of the combined rate signal and affecting factors were analyzed using a steady-state covariance. A system comprising a six-gyroscope array was developed to test the presented KF. Experimental tests proved that the presented model was effective at improving the gyroscope accuracy. The experimental results indicated that six identical gyroscopes with an ARW noise of 6.2 °/√h and a bias drift of 54.14 °/h could be combined into a rate signal with an ARW noise of 1.8 °/√h and a bias drift of 16.3 °/h, while the estimated rate signal by the random walk model has an ARW noise of 2.4 °/√h and a bias drift of 20.6 °/h. It revealed that both models could improve the angular rate accuracy and have a similar performance in static condition. In dynamic condition, the test results showed that the first-order Markov process model could reduce the dynamic errors 20% more than the random walk model.

A novel progressive wave gyroscope based on acousto-optic effects.

We propose and numerically investigate a brand-new, high-sensitivity progressive wave gyroscope based on acousto-optic effects for the measurement of rotational angular velocity. Unlike the traditional surface acoustic wave (SAW) gyroscope, which uses shifts in the SAW frequency to characterize the rotational angular velocity, this study uses acousto-optic effects to detect changes in refractive index caused by mechanical strain, measuring the angular velocity by the output optical power intensity of the optical waveguide. The three-dimensional finite element analysis method is utilized to build an SAW excitation model and optical detection model. We show that the sensitivity of the SAW gyroscope is highly dependent upon geometric parameters of the structure and that the mechanical strain induced by the progressive wave of the SAW can be effectively measured by the optical power intensity under the action of external angular velocity. The superiority of the proposed structure is substantiated by its achievement of a theoretical sensitivity of 1.8647 (mW/m2)/(rad/s) and high impact resistance of 220,000 g. By means of normalization, the sensitivity of the proposed structure can be enhanced by four orders of magnitude compared to the traditional SAW gyroscope. The novel structure combines the advantages of both conventional microscale vibrating gyroscopes and optical gyroscopes, providing a powerful solution for performance enhancement of SAW gyroscopes and, thereby, enabling application in the field of inertial devices.

Micromechanical mode-localized electric current sensor.

This paper outlines the design of a novel mode-localized electric current sensor based on a mechanically sensitive element of weakly coupled resonator systems. With the advantage of a high voltage sensitivity of weakly coupled resonator systems, the current under test is converted to voltage via a silicon shunt resistor, which causes stiffness perturbation to one resonator. The mode-localization phenomenon alters the energy distribution in the weakly coupled resonator system. A theoretical model of current sensing is established, and the performance of the current sensor is determined: the sensitivity of the electric current sensor is 567/A, the noise floor is 69.3 nA/√Hz, the resolution is 183.6 nA, and the bias instability is 81.6 nA. The mode-localized electric current sensor provides a new approach for measuring sub-microampere currents for applications in nuclear physics, including for photocurrent signals and transistor leakage currents. It could also become a key component of a portable mode-localized multimeter when combined with a mode-localized voltmeter. In addition, it has the potential for use in studying sensor arrays to achieve higher resolution.

Design of a Capacitive MEMS Accelerometer with Softened Beams.

Lower stiffness can improve the performance of capacitive-based microelectromechanical systems sensors. In this paper, softened beams, achieved by the electrostatic assembly approach, are proposed to lower the stiffness of a capacitive MEMS accelerometer. The experiments show that the stiffness of the accelerometer is reduced by 43% with softened beams and the sensitivity is increased by 72.6%. As a result, the noise of the accelerometer is reduced to 26.2 µg/√Hz with an improvement of 44.5%, and bias instability is reduced to 5.05 µg with an enhancement of 38.7%. The electrostatic assembly-based stiffness softening technique is proven to be effective and can be used in many types of MEMS devices.

An image-to-answer algorithm for fully automated digital PCR image processing.

The digital polymerase chain reaction (dPCR) is an irreplaceable variant of PCR techniques due to its capacity for absolute quantification and detection of rare deoxyribonucleic acid (DNA) sequences in clinical samples. Image processing methods, including micro-chamber positioning and fluorescence analysis, determine the reliability of the dPCR results. However, typical methods demand high requirements for the chip structure, chip filling, and light intensity uniformity. This research developed an image-to-answer algorithm with single fluorescence image capture and known image-related error removal. We applied the Hough transform to identify partitions in the images of dPCR chips, the 2D Fourier transform to rotate the image, and the 3D projection transformation to locate and correct the positions of all partitions. We then calculated each partition's average fluorescence amplitudes and generated a 3D fluorescence intensity distribution map of the image. We subsequently corrected the fluorescence non-uniformity between partitions based on the map and achieved statistical results of partition fluorescence intensities. We validated the proposed algorithms using different contents of the target DNA. The proposed algorithm is independent of the dPCR chip structure damage and light intensity non-uniformity. It also provides a reliable alternative to analyze the results of chip-based dPCR systems.