Readout Device Research Articles

CRISPR/Cas-mediated “one to more” lighting-up nucleic acid detection using aggregation-induced emission luminogens

CRISPR diagnostics are effective but suffer from low signal transduction efficiency, limited sensitivity, and poor stability due to their reliance on the trans-cleavage of single-stranded nucleic acid fluorescent reporters. Here, we present CrisprAIE, which integrates CRISPR/Cas reactions with “one to more” aggregation-induced emission luminogen (AIEgen) lighting-up fluorescence generated by the trans-cleavage of Cas proteins to AIEgen-incorporated double-stranded DNA labeled with single-stranded nucleic acid linkers and Black Hole Quencher groups at both ends (Q-dsDNA/AIEgens-Q). CrisprAIE demonstrates superior performance in the clinical nucleic acid detection of norovirus and SARS-CoV-2 regardless of amplification. Moreover, the diagnostic potential of CrisprAIE is further enhanced by integrating it with spherical nucleic acid-modified AIEgens (SNA/AIEgens) and a portable cellphone-based readout device. The improved CrisprAIE system, utilizing Q-dsDNA/AIEgen-Q and SNA/AIEgen reporters, exhibits approximately 80- and 270-fold improvements in sensitivity, respectively, compared to conventional CRISPR-based diagnostics. We believe CrisprAIE can be readily extended as a universal signal generation strategy to significantly enhance the detection efficiency of almost all existing CRISPR-based diagnostics.

OptoAssay-Light-controlled dynamic bioassay using optogenetic switches.

Circumventing the limitations of current bioassays, we introduce a light-controlled assay, OptoAssay, toward wash- and pump-free point-of-care diagnostics. Extending the capabilities of standard bioassays with light-dependent and reversible interaction of optogenetic switches, OptoAssays enable a bidirectional movement of assay components, only by changing the wavelength of light. Demonstrating exceptional versatility, the OptoAssay showcases its efficacy on various substrates, delivering a dynamic bioassay format. The applicability of the OptoAssay is successfully demonstrated by the calibration of a competitive model assay, resulting in a superior limit of detection of 8 pg ml-1, which is beyond those of conventional ELISA tests. In the future, combined with smartphones, OptoAssays could obviate the need for external flow control systems such as pumps or valves and signal readout devices, enabling on-site analysis in resource-limited settings.

Effects and optimizations of image charge technology on the imaging performance of capacitive division image readout MCP detectors

A finite element model is proposed to investigate the impact of image charge technology on the imaging performance of capacitive division image readout (C-DIR) devices. Through detailed simulation analysis, we explore the charge density of the induction layer and each electrode layer in the multilayer capacitive anode. The position nonlinearity is calculated for various resistances per square of the induction layer and substrate thicknesses. The simulation results indicate a strong linear correlation between the position nonlinearity and substrate thickness, and an exponential decay relationship with the logarithmic resistance per square of the induction layer. The C-DIR detector is experimentally tested for imaging nonlinearity and counting rate, with the resistance per square of the induction layer ranging from 0.005 to 1000 MΩ, and the substrate thickness ranging from 1 to 5 mm. The experimental results validate the simulation conclusions and reveal the impact of the “charge accumulation effect” and “shielding effect” on the imaging performance of the detector, as well as the “imaging compression” phenomenon. Optimized image charge readout technology enables the C-DIR detector to achieve an imaging nonlinearity of 1.53% in the experiment.

Integration of LSPR-based colorimetric sensing and smartphone-assisted dual read-out microfluidic paper-based analytical devices for rapid detection of Pb2+ in environmental samples

This work presents the development of metronidazole-functionalized silver nanoparticles (MTZ-AgNPs) based LSPR sensing for rapidly detecting Pb2+ions. Advanced characterization techniques provided insights into the morphological, structural, and surface properties of the MTZ-AgNPs. The sensing mechanism and selective interaction of MTZ-AgNPs with Pb2+ions were explored, elucidating the binding process. The MTZ-AgNPs-based LSPR sensor showed a very low detection limit of 0.018 μM (3.73 ppb). MTZ-AgNPs-based sensing material was also integrated with smartphone-assisted dual read-out microfluidic paper-based analytical devices (µPADs) for rapid detection of Pb2+ions. The fabricated devices were associated with color and height changes. The detection limits of developed sensors were 0.05 μM (10.36 ppb) for color change and 0.1 μM (20.72 ppb) height changes associated with dual read-out microfluidic paper-based analytical devices. The practicality of the MTZ-AgNPs-based sensing strategy was demonstrated by detecting Pb2+in various samples, including soil, rock, air particulates, and water.

Performance evaluation of a smartphone-based home test for fecal calprotection.

Fecal calprotectin (FC) serves as a non-invasive marker for the assessment of gut inflammation in patients with inflammatory bowel disease (IBD). Laboratory measurements are usually performed with immunologic methods like enzyme-linked immunosorbent assay. Recently, quantitative home tests based on the lateral flow technology with smartphones as read-out devices have been developed. We compared the quantitative and qualitative performance of the quantitative lateral flow home test Preventis SmarTest® Calprotectin Home and the immunological test used in our laboratory (Eurospital Calprest® Turbo). Fourty-five routine samples were analyzed in parallel with both tests according to the manufacturer's instructions. The read-out of the home test was performed with two smartphones (Apple iPhone 14 Pro and Samsung Galaxy XCover 5). The qualitative interpretation (positive, negative, borderline) was conducted using the cut-offs provided by the manufacturers. Statistically significant correlations with the laboratory standard method were observed for both smartphones (Spearman's rho 0.703 and 0.715, all p<0.005). The home test showed systematically higher concentrations compared to the routine assay. We found minimal qualitative agreement between the two tests (Cohen's kappas (κ)=0.323 and 0.300; p=0.003 and 0.005) showing a lower rate of positives with the home test. Both used smartphones showed good quantitative and qualitative agreement. The tests are quantitatively not interchangeable. However, the home test may be applicable for the serial follow-up management of patients with IBD. The higher rate of samples classified as negative with the home test may lead to an underestimation of affected patients.

A 4–8 GHz kinetic inductance traveling-wave parametric amplifier using four-wave mixing with near quantum-limited noise performance

Kinetic inductance traveling-wave parametric amplifiers (KI-TWPAs) have a wide instantaneous bandwidth with a near quantum-limited noise performance and a relatively high dynamic range. Because of this, they are suitable readout devices for cryogenic detectors and superconducting qubits and have a variety of applications in quantum sensing. This work discusses the design, fabrication, and performance of a KI-TWPA based on four-wave mixing in a NbTiN microstrip transmission line. This device amplifies a signal band from 4 to 8 GHz without contamination from image tones, which are produced in a separate higher frequency band. The 4–8 GHz band is commonly used to read out cryogenic detectors, such as microwave kinetic inductance detectors and Josephson junction-based qubits. We report a measured maximum gain of over 20 dB using four-wave mixing with a 1 dB gain compression point of −58 dBm at 15 dB of gain over that band. The bandwidth and peak gain are tunable by adjusting the pump-tone frequency and power. Using a Y-factor method, we measure an amplifier-added noise of 0.5 ≤ Nadded ≤ 1.5 photons from 4.5 to 8 GHz.

Wireless and Battery-Free Sensor for Interstitial Fluid Pressure Monitoring.

Congestive heart failure (CHF) is a fatal disease with progressive severity and no cure; the heart's inability to adequately pump blood leads to fluid accumulation and frequent hospital readmissions after initial treatments. Therefore, it is imperative to continuously monitor CHF patients during its early stages to slow its progression and enable timely medical interventions for optimal treatment. An increase in interstitial fluid pressure (IFP) is indicative of acute CHF exacerbation, making IFP a viable biomarker for predicting upcoming CHF if continuously monitored. In this paper, we present an inductor-capacitor (LC) sensor for subcutaneous wireless and continuous IFP monitoring. The sensor is composed of inexpensive planar copper coils defined by a simple craft cutter, which serves as both the inductor and capacitor. Because of its sensing mechanism, the sensor does not require batteries and can wirelessly transmit pressure information. The sensor has a low-profile form factor for subcutaneous implantation and can communicate with a readout device through 4 layers of skin (12.7 mm thick in total). With a soft silicone rubber as the dielectric material between the copper coils, the sensor demonstrates an average sensitivity as high as -8.03 MHz/mmHg during in vitro simulations.

A Portable Readout System for Biomarker Detection with Aptamer-Modified CMOS ISFET Array.

Biosensors based on ion-sensitive field effect transistors (ISFETs) combined with aptamers offer a promising and convenient solution for point-of-care testing applications due to the ability for fast and label-free detection of a wide range of biomarkers. Mobile and easy-to-use readout devices for the ISFET aptasensors would contribute to further development of the field. In this paper, the development of a portable PC-controlled device for detecting aptamer-target interactions using ISFETs is described. The device assembly allows selective modification of individual ISFETs with different oligonucleotides. Ta2O5-gated ISFET structures were optimized to minimize trapped charge and capacitive attenuation. Integrated CMOS readout circuits with linear transfer function were used to minimize the distortion of the original ISFET signal. An external analog signal digitizer with constant voltage and superimposed high-frequency sine wave reference voltage capabilities was designed to increase sensitivity when reading ISFET signals. The device performance was demonstrated with the aptamer-driven detection of troponin I in both reference voltage setting modes. The sine wave reference voltage measurement method reduced the level of drift over time and enabled a lowering of the minimum detectable analyte concentration. In this mode (constant voltage 2.4 V and 10 kHz 0.1Vp-p), the device allowed the detection of troponin I with a limit of detection of 3.27 ng/mL. Discrimination of acute myocardial infarction was demonstrated with the developed device. The ISFET device provides a platform for the multiplexed detection of different biomarkers in point-of-care testing.

Portable T-2 toxin biosensor based on target-responsive DNA hydrogel using water column height as readout

T-2 toxin, a hazardous mycotoxin often present in cereals and products based on cereals, poses a substantial risk to humans and animals due to its high toxicity. The development of uncomplicated, quick and highly sensitive methods for detecting T-2 toxin is imperative. In this work, a portable sensing system was constructed using water column height as a readout device in combination with a controlled release system, which allows for an accurate quantitative analysis of T-2 toxin without the need for expensive instrumentation or skilled technicians. Hyaluronic acid (HA) hydrogel was constructed by double cross-linked DNA/aptamer hybrids with polyethyleneimine (PEI) and embedded with platinum nanoparticles (Pt NPs). The aptamer specifically bound to T-2 toxin in its presence, resulting in the disruption of the hydrogel and subsequent release of the Pt NPs. These Pt NPs were later mixed with a solution of H2O2 in a confined reaction flask, leading to the decomposition of H2O2 into O2. A glass capillary tube containing a column of red water had been inserted into the cap of the reaction flask, and the low solubility of O2 led to an increase in pressure within the reaction unit, causing the red water column to rise. There is a good linear correlation between the height of the capillary liquid level and the T-2 toxin concentration in the range of 20 ng/mL to 6 μg/mL. The system has been successfully used to detect T-2 toxin in samples of barley tea and corn.

Advancing 2D reaction rate measurements in BNCT: Validation of the indirect neutron radiography method

The precise characterization of neutron beams is a cornerstone of Boron Neutron Capture Therapy (BNCT). While Instrumental Neutron Activation Analysis (INAA) is the standard technique for neutron flux measurement, it is limited in its ability to capture two-dimensional (2D) reaction rate distributions. This study aims to validate the Indirect Neutron Radiography (INR) method for 2D reaction rate quantification, addressing critical variables such as temperature sensitivity and signal fading. We designed and constructed an optimized INR platform comprising an Imaging Plate (IP), readout device, activation detectors (copper foils), and real-time temperature monitoring. Comprehensive experiments were conducted to investigate the impact of ambient temperature and fading time on IP signal reliability. A robust calibration curve was formulated, linking IP signals to dose deposition metrics, thereby enabling precise reaction rate assessments. The study found that IP signals are minimally sensitive to temperature variations (less than 0.1% change per 1 °C), but are subjected to linear fading over time, necessitating stringent temperature control and time-dependent signal corrections. A mathematical relationship between IP signals and dose deposition was established, represented by Y = 20,500 × x0.01803-21103. Application of the INR method revealed that the depth-dependent reaction rates in copper strips closely aligned with those acquired through INAA, exhibiting a relative deviation of less than 5% within a 4cm depth range inside the phantom. Our findings demonstrate that the INR method offers a robust alternative to traditional INAA for capturing 2D reaction rates, effectively addressing complexities like temperature sensitivity and signal fading. While challenges persist, particularly in the realm of measurement errors, this study lays the groundwork for further methodological refinements and broadens the scope for future research in BNCT neutron beam characterization.

Rapid analysis and classification of blue ballpoint pen inks using high-performance thin-layer chromatography and digital color analysis

Despite the rise of digitalization, the scrutiny of paper documents with stamps and signatures remains crucial, constituting 55–60 % of document examination court cases. Developing accessible and robust ink analysis techniques is an ongoing challenge for forensic scientists. To tackle issues related to the identification and classification of dye components in blue ballpoint pens, we have proposed an advanced approach that integrates high-performance thin-layer chromatography (HPTLC), digital color analysis (DCA), and hierarchical cluster analysis (HCA) for a simplified yet effective procedure.The method encompasses multiple development of TLC plates. Initial separation employs methanol:ethanol (4:1, v/v), followed by a second separation using methanol:propan-2-ol:formic acid (1:1:0.1, v/v/v) to achieve cationic dye separation. This TLC development enhances separation selectivity, contributing to a more precise clustering of pen inks. Employing advanced DCA as a processing method for HPTLC, the optimal descriptor for ink classification is identified as the difference between red (R) and green (G) color components. The proposed clustering algorithm achieved 8 distinct ink clusters, showing improved discriminative capability and a reduced variable space compared to well-established or state-of-the-art methods.The approach's robustness was demonstrated across different readout devices, including smartphones and scanners. Reproducibility tests yielded consistent clustering results, confirming the method's reliability. Moreover, the method proved effective in clustering pen ink extracts from paper substrates, showcasing its potential for real sample analysis.This HPTLC-DCA approach presents a simple, cost-effective, and high-precision solution for clustering blue pen inks, significantly enhancing accessibility in high-throughput forensic applications.

Kinetic Inductance Traveling Wave Amplifier Designs for Practical Microwave Readout Applications

A Kinetic Inductance Traveling Wave Amplifier (KIT) utilizes the nonlinear kinetic inductance of superconducting films, particularly niobium titanium nitride (NbTiN), for parametric amplification. These amplifiers achieve remarkable performance in terms of gain, bandwidth, and compression power and frequently approach the quantum limit for noise. However, most KIT demonstrations have been isolated from practical device readout systems. Using a KIT as the first amplifier in the readout chain of an unoptimized microwave SQUID multiplexer coupled to a transition-edge sensor microcalorimeter, we see an initial improvement in the flux noise [1]. One challenge in KIT integration is the considerable microwave pump power required to drive the non-linearity. To address this, we have initiated efforts to reduce the pump power by using thinner NbTiN films and an inverted microstrip transmission line design. In this article, we present the new transmission line design, fabrication procedure, and initial device characterization—including gain and added noise. These devices exhibit over 10 dB of gain with a 3 dB bandwidth of approximately 5.5–7.25 GHz, a maximum practical gain of 12 dB, and typical gain ripple under 4 dB peak to peak. We observe an appreciable impedance mismatch in the NbTiN transmission line, which is likely the source of the majority of the gain ripple. Finally, we perform an initial noise characterization and demonstrate system-added noise of three quanta or less over nearly the entire 3 dB bandwidth.

Integrating PEGylated peptide-oriented bacteria-imprinted matrix and PdPt bimetallic-doped imidazolium zeolite framework-8 for sensitive detection of Escherichia coli with smartphone readout system

Escherichia coli (E. coli) is one of the major foodborne pathogens, and its efficient isolation and detection from complex samples are crucial. Herein, we fabricated a novel hydrophilic-PEGylated peptide-oriented bacteria-imprinted PDMS matrix (HPBIM) for highly efficient capture of E. coli from complex samples. The antibody-free HPBIM possessed a hierarchical structure of imprinted cavities, which were inlaid with peptide-functionalized SiO2 (SiO2@peptide). Meanwhile, PEGylation was performed on the non-imprinted region of HPBIM to limit the non-specific absorption. So HPBIM could specifically capture target E. coli due to the synergistic effect of peptide affinity, bacteria-imprinting and PEGylation of non-imprinted region. Additionally, a new polyethylene glycol-covered / boronic acid-modified PdPt bimetallic-doped ZIF-8 (PBPPZ) was prepared for electively labeling E. coli captured by HPBIM. PBPPZ exhibited excellent peroxidase-like activity and could generate sensitive output signals, which could be further quantitatively determined by smartphone readout device. To prove the practicability, we proposed an innovative HPBIM-PBPPZ strategy, in which the HPBIM first selectively captured E. coli, then the PBPPZ specific labeled E. coli and oxidized colorless substrate into colored product, and finally the change in color was quantitatively determined by a smartphone readout device equipped with a Color Grab APP. The biomacromolecule-free HPBIM-PBPPZ strategy exhibited excellent sensitivity with limit of detection of 69 CFU mL−1 for grapefruit juice and 257 CFU mL−1 for milk, and was successfully applied in the determination of E. coli in spiked sample with recovery and relative standard deviation in the range of 88.1–106.7% and 4.0–7.8%, respectively. Therefore, we believe that the HPBIM-PBPPZ strategy has great potential to become a powerful tool for the ultrasensitive detection of pathogens in complex biological samples.

Recent Trends in Nanomaterial Based Electrochemical Sensors for Drug Detection: Considering Green Assessment.

An individual's therapeutic drug exposure level is directly linked to corresponding clinical effects. Rapid, sensitive, inexpensive, portable and reliable devices are needed for diagnosis related to drug exposure, treatment, and prognosis of diseases. Electrochemical sensors are useful for drug monitoring due to their high sensitivity and fast response time. Also, they can be combined with portable signal read-out devices for point-of-care applications. In recent years, nanomaterials such as carbon-based, carbon-metal nanocomposites, noble nanomaterials have been widely used to modify electrode surfaces due to their outstanding features including catalytic abilities, conductivity, chemical stability, biocompatibility for development of electrochemical sensors. This review paper presents the most recent advances about nanomaterials-based electrochemical sensors including the use of green assessment approach for detection of drugs including anticancer, antiviral, anti-inflammatory, and antibiotics covering the period from 2019 to 2023. The sensor characteristics such as analyte interactions, fabrication, sensitivity, and selectivity are also discussed. In addition, the current challenges and potential future directions of the field are highlighted.

Cutting‐Edge Technology for Early Intervention in Myocardial Infarction: Portable Fingertips‐Based Immunobiosensor

AbstractEarly intervention in acute myocardial infarction can minimize myocardial damage and improve patient survival. Herein, a low‐cost device‐free portable immunobiosensing platform for flexible monitoring of immediate myocardial infarction is reported. CuS‐Pt nanofragments (CuS‐Pt NFs) with high photothermal conversion efficiency (≈26.41%) are synthesized by liquid‐phase polarity‐mediated synthesis. The CuS NFs are loaded in situ with platinum (Pt) nanoreactors using a solvothermal reduction strategy, which is employed to enhance the efficiency of gas production. The resulting CuS‐Pt nanocatalysts are encapsulated within liposomes for signal cascade amplification. Specifically, cardiac troponin I (cTn I), a target biomarker in serum, is captured on pre‐modified microtiter plates and formed into a classical sandwich model. The thermo‐chemically kinetically enhanced CuS‐Pt reactor is released through a one‐step chemical treatment and transferred to a closed gas generator. Under the excitation of a near‐infrared laser emitter, the internal pressure in the gas generator device increases with time and drives the carbon quantum dot solution in the connected hose. The moving distance shows a correlation with the target concentration. This work provides a new implementation for the development of low‐cost, efficient pressure immunosensors without the requirement of a readout device.

A personal glucose meter-utilized strategy for portable and label-free detection of hydrogen peroxide

Rapid and precise detection of hydrogen peroxide (H2O2) holds great significance since it is linked to numerous physiological and inorganic catalytic processes. We herein developed a label-free and washing-free strategy to detect H2O2 by employing a hand-held personal glucose meter (PGM) as a signal readout device. By focusing on the fact that the reduced redox mediator ([Fe(CN)6]4-) itself is responsible for the final PGM signal, we developed a new PGM-based strategy to detect H2O2 by utilizing the target H2O2-mediated oxidation of [Fe(CN)6]4- to [Fe(CN)6]3- in the presence of horseradish peroxidase (HRP) and monitoring the reduced PGM signal in response to the target amount. Based on this straightforward and facile design principle, H2O2 was successfully determined down to 3.63 μM with high specificity against various non-target molecules. We further demonstrated that this strategy could be expanded to identify another model target choline by detecting H2O2 produced through its oxidation promoted by choline oxidase. Moreover, we verified its practical applicability by reliably determining extracellular H2O2 released from the breast cancer cell line, MDA-MB-231. This work could evolve into versatile PGM-based platform technology to identify various non-glucose target molecules by employing their corresponding oxidase enzymes, greatly advancing the portable biosensing technologies.

QEchemMEMS – A working electrode with high-resolution temperature sensing for studying electrochemical heat management systems

Electrochemical heat pumps are a new and interesting concept for efficient thermal energy management at the micro- and macro-scale. The development of new solutions for electrochemical heat pumps requires reliable and high-resolution measurements of the temperature changes resulting from redox reactions. A device for measuring such temperature variations, manufactured using microelectromechanical system technology, is presented and characterized in this study. The device contains a platinum working electrode suspended on a thin SixNy membrane for the electrochemical cell; this electrode also serves as a resistive thermal device (RTD). The device and temperature readout electronic implementations of the Anderson loop are characterized. The temperature coefficient of resistance is 2736 ppm/K. The theoretical noise performance is predicted and verified in practice. The voltage noise of the RTD is 28 nV, which results in a temperature measurement resolution of 1.3 mK despite a very small RTD bias current of 40 µA.

Versatile, in-line optical oxygen tension sensors for continuous monitoring during ex vivo kidney perfusion.

Integration of physiological sensing modalities within tissue and organ perfusion systems is becoming a steadily expanding field of research, aimed at achieving technological breakthrough innovations that will expand the sites and clinical settings at which such systems can be used. This is becoming possible in part due to the advancement of user-friendly optical sensors in recent years, which rely both on synthetic, luminescent sensor molecules and inexpensive, low-power electronic components for device engineering. In this article we report a novel approach towards enabling automated, continuous monitoring of oxygenation during ex vivo organ perfusion, by combining versatile flow cell components and low-power, programmable electronic readout devices. The sensing element comprises a 3D printed, miniature flow cell with tubing connectors and an affixed oxygen-sensing thin film material containing in-house developed, brightly-emitting metalloporphyrin phosphor molecules embedded within a polymer matrix. Proof-of-concept validation of this technology is demonstrated through integration within the tubing circuit of a transportable medical device for hypothermic oxygenated machine perfusion of extracted kidneys as a model for organs to be preserved as transplants.

A low-cost, portable, dual-function readout device for amplification-based point-of-need diagnostics.

The first critical step in timely disease management is rapid disease identification, which is ideally on-site detection. Of all the technologies available for disease identification, nucleic acid amplification-based diagnostics are often used due to their specificity, sensitivity, adaptability, and speed. However, the modules to interpret amplification results rapidly, reliably, and easily in resource-limited settings at point-of-need (PON) are in high demand. Therefore, we developed a portable, low-cost, and easy-to-perform device that can be used for amplification readout at PON to enable rapid yet reliable disease identification by users with minimal training.

A Soft, Adhesive Self-Healing Naked-Eye Strain/Stress Visualization Patch.

Learning about the strain/stress distribution in a material is essential to achieve its mechanical stability and proper functionality. Conventional techniques such as universal testing machines only apply to static samples with standardized geometry in laboratory environment. Soft mechanical sensors based on stretchable conductors, carbon-filled composites, or conductive gels possess better adaptability, but still face challenges from complicated fabrication process, dependence on extra readout device, and limited strain/stress mapping ability. Inspired by the camouflage mechanism of cuttlefish and chameleons, here an innovative responsive hydrogel containing light-scattering "mechano-iridophores" is developed. Force induced reversible phase separation manipulates the dynamic generation of mechano-iridophores, serving as optical indicators of local deformation. Patch-shaped mechanical sensors made from the responsive hydrogel feature fast response time (<0.4 s), high spatial resolution (≈100µm), and wide dynamic ranges (e.g., 10-150% strain). The intrinsic adhesiveness and self-healing material capability of sensing patches also ensure their excellent applicability and robustness. This combination of chemical and optical properties allows strain/stress distributions in target samples to be directly identified by naked eyes or smartphone apps, which is not yet achieved. The great advantages above are ideal for developing the next-generation mechanical sensors toward material studies, damage diagnosis, risk prediction, and smart devices.