Search

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has lasted for almost 2 years. Stemming its spread has posed severe challenges for clinical virus detection. A long turnaround time, complicated operation, and low accuracy have become bottlenecks in developing detection techniques. Adopting a direct antigen detection strategy, we developed a fast-responding and quantitative capacitive aptasensor for ultratrace nucleocapsid protein detection based on a low-cost microelectrode array (MEA) chip. Employing the solid–liquid interface capacitance with a sensitivity of picofarad level, the tiny change on the MEA surface can be definitively detected. As a result, the limit of detection reaches an ultralow level of femtogram per milliliter in different matrices. Integrated with efficient microfluidic enrichment, the response time of this sensor from the sample to the result is shortened to 15 s, completely meeting the real-time detection demand. Moreover, the wide linear range of the sensor is from 10–5 to 10–2 ng/mL, and a high selectivity of 6369:1 is achieved. After application and evaluation in different environmental and body fluid matrices, this sensor and the detection method have proved to be a label-free, real-time, easy-to-operate, and specific strategy for SARS-CoV-2 screening and diagnosis.

Cysticercosis, caused by Taenia solium infection, is a leading cause of acquired epilepsy in many developing countries. Several types of immunoassays have been developed for the detection of Taenia solium infection in both infected humans and livestock animals. However, these methods require central laboratory facilities and are both time- and labor-consuming with longer than desired turnaround time. In this work, we demonstrated that AC electrokinetics (ACEK) capacitive sensing can be used to realize point-of-care immunosensor in general, with the on-site screening of Taenia solium infection as an example here. The sensor employs interdigitated microelectrodes (IDME) functionalized with a recombinant Taenia solium antigen, rT24H, to detect anti-rT24H antibodies in clinical serum samples. ACEK capacitive sensing method interrogates the IDME sensors with a special AC signal, which serves the dual purposes of enriching target antibodies by ACEK effects and directly measuring the capacitance change induced by specific binding. First, to characterize the ACEK biosensor as an immunosensor in general, IgG in phosphate-buffered saline buffer was tested against IDME sensors functionalized with anti-IgG. The limit of detection of the sensor was 24.1 fg/mL, and the linear dynamic range was 0.1-100 pg/mL. To test the clinical usage of this sensor, ACEK capacitive sensors with rT24H probe were used to test clinical serum samples from patients with or without Taenia solium infection. The diagnostic sensitivity of the ACEK capacitive sensor for Taenia solium infection was found to be 88.24%. ACEK capacitive immunosensors have shown good potential for point-of-care diagnostics.

Although there exist tremendous needs for on-chip biofluid delivery, research in this field has yielded limited numbers of devices for real-world applications. One challenge is the difficulty for micropumps to meet the requirements of being low cost to fabricate, easy to integrate and effective for intended applications at the same time. This research focuses on AC electrothermal (ACET) micropumps based on planar interdigitated electrodes, due to their practicality in fabrication and operation, and compatibility with biochemical fluids. Our prior work has optimized the design of electrode dimensions for a fixed microchannel design. This work finds that microchannel dimensions can also affect ACET micropumps significantly, with respect to flow rate and electric impedance loading. This work first considers the constraints arising from impedance loading by ACET micropumps on power supplies, then the investigation describes several key parameters (threshold height, saturation thickness), to arrive at an appropriate microchannel geometry for the effective delivery of biofluids. The optimized microchannel is expected to incorporate well into a multifunctional lab-chip system to transport biofluids efficiently.

When the feature size of integrated circuits (ICs) reaches nanometer, nano contaminant particles (CPs) on the surface of semi-finished devices during processing may cause serious device defects, while effective real-time CP detection techniques are still unavailable, especially when the CPs are of low concentration. Using a gold interdigitated electrode fabricated on a ceramics substrate, a sensitive sensor for ultra-trace nano CP detection in cleaning fluids is developed, which employs an optimized detection signal integrating the nanofluidic enrichment of nanoparticles (NPs) into interfacial capacitance measurement. The detection can achieve a limit of detection of 102 particles/mL with a response time of 30 s. The logarithmic linear range of this sensor reaches (102 - 107) particles/mL for CPs of 10 nm in grain diameter, which can meet the test demand of practical concentration. This sensor has capability to detect CPs of different material and size, and the operation is real-time and nondestructive. In addition, it is demonstrated to work reliably in solutions with different conductivity. The detection protocol is simple, and the sensor as well as the impedance analyzer for test also has advantages in portability and cost efficiency for industrial-scale on line application. This work provides a feasible and promising approach for IC fabrication’s quality evaluation through ultra-trace nano CP detection in used cleaning liquid samples.

This work presents a sensitive and specific single-step RNA sensor for Zika virus (ZIKV) in serum. Using AC electrokinetics (ACEK)-enhanced capacitive sensing technology, ZIKV genomic RNA (gRNA) can be directly detected from serum. The sensors are interdigitated electrodes modified with oligonucleotide probes complementary to the conserved regions of ZIKV gRNA. The ACEK capacitive sensing applies an optimized AC excitation signal over the sensor, which induces ACEK microfluidic enrichment of analytes and also simultaneously performs real-time monitoring of hybridization of ZIKV gRNA on the sensor surface. Hence, the sensing procedures are simple with rapid turn-around time and good specificity and sensitivity. A series of experiments are conducted to optimize the sensor performance. The performance of the sensor is investigated for three different probes, two functionalization buffers, and different hybridization buffers. With the optimized sensing protocol, this method can detect spiked ZIKV gRNA from human serum within 30 s and reach a limit of detection of 78.8 copies/μL in analytical samples and as low as 287.5 copies/μL in neat serum. The sensors can successfully differentiate between the RNAs of the ZIKV and dengue virus, two viruses with similar transmission paths and symptoms. The sensor is simple to use and requires no labeling or sophisticated process typically involved in a polymerase chain reaction, hybridization chain reaction, or nucleic acid sequence-based amplification.

Disposable point-of-care biomedical applications demand low-cost biosensing systems that can provide rapid detection with accessible fabrication requirements and user-friendly operation. Here, we present an easy-to-operate and cleanroom-free desktop-fabricated biosensor that is capable of reliable detection for human D-dimer biomarkers on-site. Interdigitated electrodes are used as the biosensor, and they are fabricated using commercial compact discs and home-made gadgets. The compact disc-based electrode arrays are patterned by wet-etching and followed by electroplating of polypyrrole (PPy). The nano-porous structures of PPy enhance the immobilization of protein probe on the electrode surface. The sensor performance is further enhanced by the ac electrokinetics (ACEK) capacitive sensing method. ACEK capacitive sensing induces ACEK effects that direct analytes toward the electrode surfaces, significantly promoting probe-target binding. Our sensor can quantitatively detect D-dimer biomarkers in 1 min with a limit of detection of 1 pg/mL. In contrast, Nyquist or Bode plots can only qualitatively distinguish positive and negative samples. Furthermore, the total cost of each test, together with the lithography material and compact disk, is only around U.S. $1, and it is acceptable to be disposable. The sensitive device yields wide-ranging and significant advantages for biomedical and lab-on-a-chip applications for undeveloped areas.

Biosensors have shown great potential in realizing rapid, low cost and portable on-site detection for diseases. This work reports the development of a new bioelectronic sensor called AC electrokinetics-based capacitive (ABC) biosensor, for the detection of genomic DNA (gDNA) of methicillin-resistant Staphylococcus aureus (MRSA). The ABC sensor is based on interdigitated microelectrodes biofunctionalized with oligonucleotide probes. It uses a special AC signal for direct capacitive monitoring of topological change on nanostructured sensor surface, which simultaneously induce dieletrophoretic enrichment of target gDNAs. As a result, rapid and specific detection of gDNA/probe hybridization can be realized with high sensitivity. It requires no signal amplification such as labelling, hybridization chain reaction, or nucleic acid sequence-based amplification. This method involves only simple sample preparation. After optimization of nano-structured sensor surface and signal processing, the ABC sensor demonstrated fast turnaround of results (~10 s detection), excellent sensitivity (a detection limit of 4.7 DNA copies /µL MRSA gDNA) and high specificity, suitable for point of care diagnosis. As a bioelectronic sensor, the developed ABC sensors can be easily adapted for detection of other infectious agents.

A wirelessly powered and controlled biased-AC electroosmotic (biased-ACEO) lab-on-a-film (LOF) is presented here for particle and fluid manipulation. Amplitude modulation (AM) and inductive coupling are used for wireless transmission of low frequency signals required for excitation of biased-ACEO effects employed by the LOF for microfluidic functions. The LOF consists of a receiving coil (for receiving inductively transmitted high frequency signals), surface mounted devices (for recovering a low frequency AC signal) and an array of interdigitated electrodes (IDE, for excitation of biased-ACEO effects). Unlike existing wireless lab-on-a-chip devices that have cumbersome set-ups, require high voltages and perform only one microfluidic function, the presented LOF has a compact and flexible structure, works at very low voltage ranges, and can perform several microfluidic operations corresponding to a wirelessly-controlled voltage. When the level of the demodulated signal over the IDE is about 0.7 V, the IDE performs particle enrichment over designated electrodes. The IDE functions as an active mixer at about 2 V; and as a pump when the voltage reaches 3 V. The LOF is prototyped rapidly on a flexible substrate at low cost using inexpensive benchtop equipment with an overall dimension of 10 × 20 mm2. Though the electrode definition is limited to micro-scales, the LOF prototype has successfully demonstrated desired microfluidic functions. In addition to inductive transmission of low frequency signals, the printed circuit board-based LOF device offers a low cost and effective solution for using small, flexible microfluidic systems in nontraditional clinical diagnostic tools, disposable devices and heath care settings.

AC electrokinetics (ACEK) has been shown to deliver certain drugs into human teeth more effectively than diffusion. However, using electrical wires to power intraoral ACEK devices poses risks to patients. The study demonstrates a novel interdigitated electrode arrays (IDE) assembly powered by inductive coupling to induce ACEK effects at appropriate frequencies to motivate drugs wirelessly. A signal generator produces the modulating signal, which multiplies with the carrier signal to produce the amplitude modulated (AM) signal. The AM signal goes through the inductive link to appear on the secondary coil, then rectified and filtered to dispose of its carrier signal, and the positive half of the modulating signal appears on the load. After characterizing the device, the device is validated under light microscopy by motivating carboxylate-modified microspheres, tetracycline, acetaminophen, benzocaine, lidocaine and carbamide peroxide particles with induced ACEK effects. The assembly is finally tested in a common dental bleaching application. After applying 35 % carbamide peroxide to human teeth topically or with the IDE at 1200 Hz, 5 Vpp for 20 min, spectrophotometric analysis showed that compared to diffusion, the IDE enhanced whitening in specular optic and specular optic excluded modes by 215 % and 194 % respectively. Carbamide peroxide absorbance by the ACEK group was two times greater than diffusion as measured by colorimetric oxidation-reduction and UV-Vis spectroscopy at 550 nm. The device motivates drugs of variable molecular weight and structure wirelessly. Wireless transport of drugs to intraoral targets under ACEK effects may potentially improve the efficacy and safety of drug delivery in dentistry.

"Inductively Coupled Deep Brain Stimulator" describes a chip/system design to inductively couple arbitrary waveforms to electrodes embedded in the brain for deep brain stimulation or other neurostimulation. This approach moves the conventionally implanted signal generator outside the body and provides flexibility in adjusting waveforms to investigate optimum stimulation waveforms. An "inlaid electroplating" process with through-wafer plating is used to reduce microcoil resistance and integrate microstructures and electronics. Utilizing inductive link resonance specific to microcoils, waveforms are selectively transmitted to microcoils, which further produces biphasic waveforms that are suitable for deep brain stimulation.