High sensitivity saliva-based biosensor in detection of breast cancer biomarkers: HER2 and CA15-3.

The prevalence of breast cancer in women underscores the urgent need for innovative and efficient detection methods. This study addresses this imperative by harnessing salivary biomarkers, offering a noninvasive and accessible means of identifying breast cancer. In this study, commercially available disposable based strips similar to the commonly used glucose detection strips were utilized and functionalized to detect breast cancer with biomarkers of HER2 and CA15-3. The results demonstrated limits of detection for these two biomarkers reached as low as 1 fg/ml much lower than those of conventional enzyme-linked immunosorbent assay in the range of 1∼4 ng/ml. By employing a synchronized double-pulse method to apply 10 of 1.2 ms voltage pulses to the electrode of sensing strip and drain electrode of the transistor for amplifying the detected signal, and the detected signal was the average of 10 digital output readings corresponding to those 10 voltage pulses. The sensor sensitivities were achieved approximately 70/dec and 30/dec for HER2 and CA15-3, respectively. Moreover, the efficiency of this novel technique is underscored by its swift testing time of less than 15 ms and its minimal sample requirement of only 3 µl of saliva. The simplicity of operation and the potential for widespread public use in the future position this approach as a transformative tool in the early detection of breast cancer. This research not only provides a crucial advancement in diagnostic methodologies but also holds the promise of revolutionizing public health practices.

Detection of lactate in human sweat via surface-modified, screen-printed carbon electrodes.

Real-time and continuous monitoring of lactate levels in sweat has been used as an indicator of physiological information to evaluate exercise outcomes and sports performance. We developed an optimal enzyme-based biosensor to detect the concentrations of lactate in different fluids (i.e., a buffer solution and human sweat). The surface of the screen-printed carbon electrode (SPCE) was first treated with oxygen plasma and then surface-modified by lactate dehydrogenase (LDH). The optimal sensing surface of the LDH-modified SPCE was identified by Fourier transform infrared spectroscopy and electron spectroscopy for chemical analysis. After connecting the LDH-modified SPCE to a benchtop E4980A precision LCR meter, our results showed that the measured response was dependent on the lactate concentration. The recorded data exhibited a broad dynamic range of 0.1-100 mM (R2 = 0.95) and a limit of detection of 0.1 mM, which was unachievable without the incorporation of redox species. A state-of-the-art electrochemical impedance spectroscopy (EIS) chip was developed to integrate the LDH-modified SPCE for a portable bioelectronic platform in the detection of lactate in human sweat. We believe the optimal sensing surface can improve the sensitivity of lactate sensing in a portable bioelectronic EIS platform for early diagnosis or real-time monitoring during different physical activities.

A Multimodality Electrochemical and Impedance Spectroscopy System-on-a-Chip With Temperature Sensing and Impedance-Boosting Techniques.

This article presents a multimodal electrochemical sensing system-on-chip (SoC), including the functions of cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and temperature sensing. CV readout circuitry achieves an adaptive readout current range of 145.5 dB through an automatic range adjustment and resolution scaling technique. EIS has an impedance resolution of 9.2 m Ω/√ Hz at a sweep frequency of 10 kHz and an output current of up to 120 µA. With an impedance boost mechanism, the maximum detectable load impedance is extended to 22.95 k Ω, while the total harmonic distortion is less than 1%. A resistor-based temperature sensor using a swing-boosted relaxation oscillator can achieve a resolution of 31 mK in 0-85 °C. The design is implemented in a 0.18 µm CMOS process. The total power consumption is 1 mW.

High sensitivity CIP2A detection for oral cancer using a rapid transistor-based biosensor module.

Oral squamous cell carcinoma (OSCC) is one of the most common lip and oral cavity cancer types. It requires early detection via various medical technologies to improve the survival rate. While most detection techniques for OSCC require testing in a centralized lab to confirm cancer type, a point of care detection technique is preferred for on-site use and quick result readout. The modular biological sensor utilizing transistor-based technology has been leveraged for testing CIP2A, and optimal transistor gate voltage and load resistance for sensing setup was investigated. Sensitivities of 1 × 10-15 g/ml have been obtained for both detections of pure CIP2A protein and HeLa cell lysate using identical test conditions via serial dilution. The superior time-saving and high accuracy testing provides opportunities for rapid clinical diagnosis in the medical space.

A Wireless Soil pH and Conductance Monitoring Chip Powered by Soil Microbial and Photovoltaic Energy Cells.

This paper presents an energy-autonomous wireless soil pH and electrical conductance measurement IC powered by soil microbial and photovoltaic energy. The chip integrates highly efficient dual-input, dual-output power management units, sensor readout circuits, a wireless receiver, and a transmitter. The design scavenges ambient energy with a maximal power point tracking mechanism while achieving a peak efficiency of 81.3% and the efficiency is more than 50% over the 0.05-14 mW load range. The sensor readout IC achieves a sensitivity of -8.8 kHz/pH and 6 kHz·m/S, a noise floor of 0.92 x 10-3 pH value, and 1.4 mS/m conductance. To avoid interference, a 433 MHz transceiver incorporates chirp modulation and on-off keying (OOK) modulation for data uplink and downlink communication. The receiver sensitivity is -80 dBm, and the output transmission power is -4 dBm. The uplink data rate is 100 kb/s using burst chirp modulation and gated Class E PA, while the downlink data rate is 10 kb/s with a self-frequency tracking mixer-first receiver.

Digital biosensor for human cerebrospinal fluid detection with single-use sensing strips.

Leakage of human cerebrospinal fluid (CSF) caused by trauma or other reasons presents exceptional challenges in clinical analysis and can have severe medical repercussions. Conventional test methods, including enzyme-linked immunosorbent assay and immunofixation electrophoresis testing, typically are performed at a few clinical reference laboratories, which may potentially delay proper diagnosis and treatment. At the same time, medical imaging can serve as a secondary diagnosis tool. This work presented here reports the use of a point-of-care electrochemical sensor for detection of beta-2-transferrin (B2T), a unique isomer of transferrin that is present exclusively in human CSF but is absent in other bodily fluids. Limits of detection were examined via serial dilution of human samples with known B2T concentrations down to 7 × 10-12 g B2T/ml while maintaining excellent sensitivity. Nine human samples with varying levels of B2T were compared using up to 100 times dilution to confirm the validity of sensor output across different patient samples.

Rapid SARS-CoV-2 diagnosis using disposable strips and a metal-oxide-semiconductor field-effect transistor platform.

The SARS-CoV-2 pandemic has had a significant impact worldwide. Currently, the most common detection methods for the virus are polymerase chain reaction (PCR) and lateral flow tests. PCR takes more than an hour to obtain the results and lateral flow tests have difficulty with detecting the virus at low concentrations. In this study, 60 clinical human saliva samples, which included 30 positive and 30 negative samples confirmed with RT-PCR, were screened for COVID-19 using disposable glucose biosensor strips and a reusable printed circuit board. The disposable strips were gold plated and functionalized to immobilize antibodies on the gold film. After functionalization, the strips were connected to the gate electrode of a metal-oxide-semiconductor field-effect transistor on the printed circuit board to amplify the test signals. A synchronous double-pulsed bias voltage was applied to the drain of the transistor and strips. The resulting change in drain waveforms was converted to digital readings. The RT-PCR-confirmed saliva samples were tested again using quantitative PCR (RT-qPCR) to determine cycling threshold (Ct) values. Ct values up to 45 refer to the number of amplification cycles needed to detect the presence of the virus. These PCR results were compared with digital readings from the sensor to better evaluate the sensor technology. The results indicate that the samples with a range of Ct values from 17.8 to 35 can be differentiated, which highlights the increased sensitivity of this sensor technology. This research exhibits the potential of this biosensor technology to be further developed into a cost-effective, point-of-care, and portable rapid detection method for SARS-CoV-2.

Wireless Multimodality Sensing System-on-a-Chip With Time-Based Resolution Scaling Technique and Analog Waveform Generator in 0.18 µm CMOS for Chronic Wound Care.

Multimodal sensing can provide a comprehensive and accurate diagnosis of biological information. This paper presents a fully integrated wireless multimodal sensing chip with voltammetric electrochemical sensing at a scanning rate range of 0.08-400 V/s, temperature monitoring, and bi-phasic electrical stimulation for wound healing progress monitoring. The time-based readout circuitry can achieve a 1-20X scalable resolution through dynamic threshold voltage adjustment. A low-noise analog waveform generator is designed using current reducer techniques to eliminate the large passive components. The chip is fabricated via a 0.18 µm CMOS process. The design achieves R2 linearity of 0.995 over a wide current detection range (2 pA-12 µA) while consuming 49 µW at 1.2 V supply. The temperature sensing circuit achieves a 43 mK resolution from 20 to 80 degrees. The current stimulator provides an output current ranging from 8 µA to 1 mA in an impedance range of up to 3 kΩ. A wakeup receiver with data correlators is used to control the operation modes. The sensing data are wirelessly transmitted to the external readers. The proposed sensing IC is verified for measuring critical biomarkers, including C-reactive protein, uric acid, and temperature.

Dry Wearable Textile Electrodes for Portable Electrical Impedance Tomography.

Electrical impedance tomography (EIT), a noninvasive and radiation-free medical imaging technique, has been used for continuous real-time regional lung aeration. However, adhesive electrodes could cause discomfort and increase the risk of skin injury during prolonged measurement. Additionally, the conductive gel between the electrodes and skin could evaporate in long-term usage and deteriorate the signal quality. To address these issues, in this work, textile electrodes integrated with a clothing belt are proposed to achieve EIT lung imaging along with a custom portable EIT system. The simulation and experimental results have verified the validity of the proposed portable EIT system. Furthermore, the imaging results of using the proposed textile electrodes were compared with commercial electrocardiogram electrodes to evaluate their performance.

Bio-inspired fractal textile device for rapid sweat collection and monitoring.

In this study, a new design concept in sweat collection was developed to achieve rapid and intact sweat sampling for analytical purposes. Textiles with fast water wicking properties were first selected and laser engraved into tree-like bifurcating channels for sweat collection. The fractal framework of the bifurcating textile channels was theoretically derived to minimize the flow resistance for fast sweat absorption. The optimized collector with designed fractal geometry exhibited thorough coverage of emerging droplets without overflow. Great collection efficiency was achieved with a short induction time (<1 minute after perspiration begins) and a maximum sweat collection flux up to 4.0 µL cm-2 min-1 without leakage. After being combined with printed sensors and microchips, the assembled sweat collection/sensing device can simultaneously provide measurements of salt concentration and sweat rate for wireless hydration state monitoring. The collection/sensing system also exhibited fast response times to abrupt changes in sweat rates or concentrations and thus can be used to detect instant physical conditions in exercise. Finally, field tests were performed to demonstrate the reliability and practicality of the device in real-time sweat monitoring under vigorous activities.

Fast SARS-CoV-2 virus detection using disposable cartridge strips and a semiconductor-based biosensor platform.

Detection of the SARS-CoV-2 spike protein and inactivated virus was achieved using disposable and biofunctionalized functional strips, which can be connected externally to a reusable printed circuit board for signal amplification with an embedded metal-oxide-semiconductor field-effect transistor (MOSFET). A series of chemical reactions was performed to immobilize both a monoclonal antibody and a polyclonal antibody onto the Au-plated electrode used as the sensing surface. An important step in the biofunctionalization, namely, the formation of Au-plated clusters on the sensor strips, was verified by scanning electron microscopy, as well as electrical measurements, to confirm successful binding of thiol groups on this Au surface. The functionalized sensor was externally connected to the gate electrode of the MOSFET, and synchronous pulses were applied to both the sensing strip and the drain contact of the MOSFET. The resulting changes in the dynamics of drain waveforms were converted into analog voltages and digital readouts, which correlate with the concentration of proteins and virus present in the tested solution. A broad range of protein concentrations from 1 fg/ml to 10 µg/ml and virus concentrations from 100 to 2500 PFU/ml were detectable for the sensor functionalized with both antibodies. The results show the potential of this approach for the development of a portable, low-cost, and disposable cartridge sensor system for point-of-care detection of viral diseases.

A 19 µW, 50 kS/s, 0.008-400 V/s Cyclic Voltammetry Readout Interface With a Current Feedback Loop and On-Chip Pattern Generation.

A cyclic voltammetry electrochemical sensing chip was implemented with a time-based readout circuit and a current feedback control loop for wide-range and high-linearity current detection. The design utilizes a chopper-stabilized, low-noise potentiostat circuit and a delay chain time-to-digital converter to improve accuracy and the conversion rate. A current feedback loop is employed to mitigate nonlinearity of the current-to-frequency converter. Also, an on-chip pattern generator with a current reducer is used to create area-efficient, multi-rate ramp signals for cyclic voltammetry and fast-scan cyclic voltammetry measurements. The chip is fabricated using a 0.18-µm CMOS process. It achieves an 8-nA current resolution in the current range of -7 µA to 10 µA with an R2 linearity of 0.999 while consuming 19 µW. The Allan deviation floor is 4.83 Hz at the 7-second integration window, resulting in an 87-pArms input-referred current noise. The applicable limit of detection for K3[Fe(CN)6] concentration is 31 pM. To measure various reactions, the scan rate can be adjusted from 0.008 V/s to 400 V/s with a throughput data rate of up to 50 kS/s.

A Two-Electrode, Double-Pulsed Sensor Readout Circuit for Cardiac Troponin I Measurement.

This paper presents a pulse-stimulus sensor readout circuit for use in cardiovascular disease examinations. The sensor is based on a gold nanoparticle plate with an antibody post-modification. The proposed system utilizes gated pulses to detect the biomarker Cardiac Troponin I in an ionic solution. The characteristic of the electrostatic double-layer capacitor generated by the analyte is related to the concentration of Cardiac Troponin I in the solvent. After sensing by the transistor, a current-to-frequency converter (I-to-F) and delay-line-based time-to-digital converter (TDC) convert the information into a series of digital codes for further analysis. The design is fabricated in a 0.18-µm standard CMOS process. The chip occupies an area of 0.92 mm2 and consumes 125 µW. In the measurements, the proposed circuit achieved a 1.77 Hz/pg-mL sensitivity and 72.43 dB dynamic range.

A Microwatt Dual-Mode Electrochemical Sensing Current Readout With Current-Reducer Ramp Waveform Generation.

An electrochemical sensing chip with an integrated current-reducer pattern generator and a current-mirror based low-noise chopper-stabilization potentiostat circuit is presented. The pattern generator, utilizing the current reducer technique and pseudo resistors, creates a sub-Hz ramp signal for the cyclic voltammetric (CV) measurement without large-size passive components. The proposed design adopts the chopper-stabilization and low-noise biasing technique for the potentiostat and a counter-based time-to-digital converter to reduce the amplitude noise effects and to convert the sensing current signal to digital codes for further data processing. The design is fabricated using a 0.18-µm CMOS process and achieves a 41 pA current resolution in the current range of ±5 µA while maintaining the R2 linearity of 0.998. The system consumes 16 µW from a 1.2 V supply when a 5 µA sensing current is detected. The power efficiency of the readout interface is 0.31, and the sensing current dynamic range is 108 dB. The design is fully integrated into a single chip and is successfully tested in the dual-mode (CA/CV) measurements with commercial gold electrodes in a potassium ferricyanide solution in sub-millimolar concentrations.

Enhancing Efficiency and Stability of Photovoltaic Cells by Using Perovskite/Zr-MOF Heterojunction Including Bilayer and Hybrid Structures.

In this study, the effectiveness of using a perovskite/Zr-metal-organic frameworks (MOFs) heterojunction in realizing efficient and stable inverted p-i-n perovskite solar cells (PVSCs) is demonstrated. Two types of Zr-MOFs, UiO-66 and MOF-808, are investigated owing to their respectable moisture and chemical stabilities. The MOFs while serving as an interlayer in conjunction with the perovskite film are shown to possess the advantages of UV-filtering capability and enhancing perovskite crystallinity. Consequently, the UiO-66/MOF-808-modified PVSCs yield enhanced power conversion efficiencies (PCEs) of 17.01% and 16.55%, outperforming the control device (15.79%). While further utilizing a perovskite/Zr-MOF hybrid heterojunction to fabricate the devices, the hybrid MOFs are found to possibly distribute over the perovskite grain boundary providing a grain-locking effect to simultaneously passivate the defects and to reinforce the film's robustness against moisture invasion. As a result, the PCEs of the UiO-66/MOF-808-hybrid PVSCs are further enhanced to 18.01% and 17.81%, respectively. Besides, over 70% of the initial PCE is retained after being stored in air (25 °C and relative humidity of 60 ± 5%) for over 2 weeks, in contrast to the quick degradation observed for the control device. This study demonstrates the promising potential of using perovskite/MOF heterojunctions to fabricate efficient and stable PVSCs.

Design and Study of a Portable High-frequency Ventilator for Clinical Applications.

Treatment costs for ventilator-dependent patients are a substantial burden not only for their family but also for medical systems in general. Recently, using high-frequency ventilators have been shown to reduce the risk of lung injury through low-volume airflow. However, the machines used today remain bulky, costly, and only for use in hospital settings. To provide intermediate therapy for patients between hospitalization and complete discharge, a portable, light-weight high-frequency ventilator is an urgent need. This work presents the design of a portable high-frequency ventilator and a study of its practicality for further clinical medical applications. Through the integration of advanced electronics and mechanical instruments, we develop a portable high-frequency ventilator with reconfigurable oxygen flow rate, applied pressure, and air volume for the needs of individual patients. A miniaturized portable high-frequency ventilator with digital controller and feedback system for stabilization and precision control is implemented. The efficiency of CO2 washout using the proposed ventilator has been demonstrated in animal trials.

A Reconfigurable, Pulse-shaping Potentiometric Readout System for Bio-Sensing Transistors.

This paper presents a new multi-modality readout system for potentiometric electrochemical sensors. The design adopts a pulse modulation at the gate and drain of the Bio-FET sensors to reduce the effects of charge accumulation between the surface of the electrodes and the ion analytes. The adjustable duration and amplitude of stimuli signals provide flexibility for different biosensing applications and a wide range of detectable concentration. Also, an oscillator-based architecture is proposed for digitization and integration. The counting time can be adjusted to enhance the resolution of the readout system. The proposed potentiometric sensing system was tested with 0.1-10 mM Potassium Ferricyanide (K3[Fe(CN)6]), and the results are interpreted in the micro-LCD on the board. The design offers the opportunity for a handheld medical device with fast and real-time monitoring of biomarkers and ion analytes.

Enhanced Charge Collection in MOF-525-PEDOT Nanotube Composites Enable Highly Sensitive Biosensing.

With the aim of a reliable biosensing exhibiting enhanced sensitivity and selectivity, this study demonstrates a dopamine (DA) sensor composed of conductive poly(3,4-ethylenedioxythiophene) nanotubes (PEDOT NTs) conformally coated with porphyrin-based metal-organic framework nanocrystals (MOF-525). The MOF-525 serves as an electrocatalytic surface, while the PEDOT NTs act as a charge collector to rapidly transport the electron from MOF nanocrystals. Bundles of these particles form a conductive interpenetrating network film that together: (i) improves charge transport pathways between the MOF-525 regions and (ii) increases the electrochemical active sites of the film. The electrocatalytic response is measured by cyclic voltammetry and differential pulse voltammetry techniques, where the linear concentration range of DA detection is estimated to be 2 × 10-6-270 × 10-6 m and the detection limit is estimated to be 0.04 × 10-6 m with high selectivity toward DA. Additionally, a real-time determination of DA released from living rat pheochromocytoma cells is realized. The combination of MOF5-25 and PEDOT NTs creates a new generation of porous electrodes for highly efficient electrochemical biosensing.

Mesoporous TiO2 Embedded with a Uniform Distribution of CuO Exhibit Enhanced Charge Separation and Photocatalytic Efficiency.

Mixed metal oxide nanoparticles have interesting physical and chemical properties, but synthesizing them with colloidal methods is still challenging and often results in very heterogeneous structures. Here, we describe a simple method to synthesize mesoporous titania nanoparticles implanted with a uniform distribution of copper oxide nanocrystals (CuO@MTs). By calcining a titanium-based metal-organic framework (MIL-125) in the presence of Cu ions, we can trap the Cu in the TiO2 matrix. Removal of the organic ligand creates mesoporosity and limits phase separation so that tiny CuO nanocrystals form in the interstices of the TiO2. The CuO@MTs exhibits superior performance for photocatalytic hydrogen evolution (4760 µmol h-1) that is >90 times larger than pristine titania.

Trifunctional Fe3O4/CaP/Alginate Core-Shell-Corona Nanoparticles for Magnetically Guided, pH-Responsive, and Chemically Targeted Chemotherapy.

Chemotherapy of bladder cancer has limited efficacy because of the short retention time of drugs in the bladder during therapy. In this research, nanoparticles (NPs) with a new core/shell/corona nanostructure have been synthesized, consisting of iron oxide (Fe3O4) as the core to providing magnetic properties, drug (doxorubicin) loaded calcium phosphate (CaP) as the shell for pH-responsive release, and arginylglycylaspartic acid (RGD)-containing peptide functionalized alginate as the corona for cell targeting (with the composite denoted as RGD-Fe3O4/CaP/Alg NPs). We have optimized the reaction conditions to obtain RGD-Fe3O4/CaP/Alg NPs with high biocompatibility and suitable particle size, surface functionality, and drug loading/release behavior. The results indicate that the RGD-Fe3O4/CaP/Alg NPs exhibit enhanced chemotherapy efficacy toward T24 bladder cancer cells, owing to successful magnetic guidance, pH-responsive release, and improved cellular uptake, which give these NPs great potential as therapeutic agents for future in vivo drug delivery systems.