Flexible and multi-functional three-dimensional scaffold based on enokitake-like Au nanowires for real-time monitoring of endothelial mechanotransduction.

Endothelial cells are sensitive to mechanical force and can convert it into biochemical signals to trigger mechano-chemo-transduction. Although conventional techniques have been used to investigate the subsequent modifications of cellular expression after mechanical stimulation, the in situ and real-time acquiring the transient biochemical information during mechanotransduction process remains an enormous challenge. In this work, we develop a flexible and multi-functional three-dimensional conductive scaffold that integrates cell growth, mechanical stimulation, and electrochemical sensing by in situ growth of enokitake-like Au nanowires on a three-dimensional porous polydimethylsiloxane substrate. The conductive scaffold possesses stable and desirable electrochemical sensing performance toward nitric oxide under mechanical deformation. The prepared e-AuNWs/CC/PDMS scaffold exhibits a good electrocatalytic ability to NO with a linear range from 2.5 nM to 13.95 µM and a detection limit of 8 nM. Owing to the excellent cellular compatibility, endothelial cells can be cultured directly on the scaffold and the real-time inducing and recording of nitric oxide secretion under physiological and pathological conditions were achieved. This work renders a reliable sensing platform for real-time monitoring cytomechanical signaling during endothelial mechanotransduction and is expected to promote other related biological investigations based on three-dimensional cell culture.

Continuous oxygen monitoring to enhance ex-vivo organ machine perfusion and reconstructive surgery.

Continuous oxygenation monitoring of machine-perfused organs or transposed autologous tissue is not currently implemented in clinical practice. Oxygenation is a critical parameter that could be used to verify tissue viability and guide corrective interventions, such as perfusion machine parameters or surgical revision. This work presents an innovative technology based on oxygen-sensitive, phosphorescent metalloporphyrin allowing continuous and non-invasive oxygen monitoring of ex-vivo perfused vascularized fasciocutaneous flaps. The method comprises a small, low-energy optical transcutaneous oxygen sensor applied on the flap's skin paddle as well as oxygen sensing devices placed into the tubing. An intermittent perfusion setting was designed to study the response time and accuracy of this technology over a total of 54 perfusion cycles. We further evaluated correlation between the continuous oxygen measurements and gold-standard perfusion viability metrics such as vascular resistance, with good agreement suggesting potential to monitor graft viability at high frequency, opening the possibility to employ feedback control algorithms in the future. This proof-of-concept study opens a range of research and clinical applications in reconstructive surgery and transplantation at a time when perfusion machines undergo rapid clinical adoption with potential to improve outcomes across a variety of surgical procedures and dramatically increase access to transplant medicine.

Flexible Sensor for Real-Time Monitoring of Motion Artifacts in Magnetic Resonance Imaging.

In recent years, magnetic resonance imaging has been widely used in the medical field. During the scan, if the human body moves, then there will be motion artifacts on the scan image, which will interfere with the diagnosis and only be found after the end of the scan sequence, resulting in a waste of manpower and resources. However, there is a lack of technology that halts scanning once motion artifacts arise. Here, we designed a real-time monitoring sensor (RMS) to dynamically perceive the movement of the human body and to pause in time when the movement exceeds a certain amplitude. The sensor has an array structure that can accurately sense the position of the human body in real time. The selection of the RMS ensures that there is no additional interference with the scanning results. Based on this design, the RMS can achieve the monitoring function of motion artifact generation.

Human-Inspired Tactile Perception System for Real-Time and Multimodal Detection of Tactile Stimuli.

A human can intuitively perceive and comprehend complicated tactile information because the cutaneous receptors distributed in the fingertip skin receive different tactile stimuli simultaneously and the tactile signals are immediately transmitted to the brain. Although many research groups have attempted to mimic the structure and function of human skin, it remains a challenge to implement human-like tactile perception process inside one system. In this study, we developed a real-time and multimodal tactile system that mimics the function of cutaneous receptors and the transduction of tactile stimuli from receptors to the brain, by using multiple sensors, a signal processing and transmission circuit module, and a signal analysis module. The proposed system is capable of simultaneously acquiring four types of decoupled tactile information with a compact system, thereby enabling differentiation between various tactile stimuli, texture characteristics, and consecutive complex motions. This skin-like three-dimensional integrated design provides further opportunities in multimodal tactile sensing systems.

Portable Conductometric Sensing Probe for Real-Time Monitoring Ammonia Profile in Coastal Waters.

An ability to real-time and continuously monitor ammonium/ammonia profiles of coastal waters over a prolonged period in a simple and maintenance-free fashion would enable economic conducting large-scale assessments, providing the needed scientific insights to better control and mitigate the impact of eutrophication on coastal ecosystems. However, this is a challenging task due to the lack of capable sensors. Here, we demonstrate the use of a membrane-based conductometric ammonia sensing probe (CASP) for real-time monitoring of ammonia levels in coastal waters. A boric acid/glycerol receiving phase is investigated and innovatively utilized to overcome the high salinity of coastal water-induced analytical errors. A calibration-free approach is used to eliminate the need for ongoing calibration, while the issues concerning practical applications, such as salinity variation, ammonia intake capability, and biofouling, are systematically investigated. The field deployment at an estuary confluence water site over a half-moon cycle period confirms that CASP is capable of continuously monitoring the ammonia profile of coastal waters in real-time with high resolution and accuracy to unveil the dynamic ammonia concentration changes over a prolonged period.

Electrochemical and Optical Sensors for Real-Time Detection of Nitrate in Water.

The health and integrity of our water sources are vital for the existence of all forms of life. However, with the growth in population and anthropogenic activities, the quality of water is being impacted globally, particularly due to a widespread problem of nitrate contamination that poses numerous health risks. To address this issue, investigations into various detection methods for the development of in situ real-time monitoring devices have attracted the attention of many researchers. Among the most prominent detection methods are chromatography, colorimetry, electrochemistry, and spectroscopy. While all these methods have their pros and cons, electrochemical and optical methods have emerged as robust and efficient techniques that offer cost-effective, accurate, sensitive, and reliable measurements. This review provides an overview of techniques that are ideal for field-deployable nitrate sensing applications, with an emphasis on electrochemical and optical detection methods. It discusses the underlying principles, recent advances, and various measurement techniques. Additionally, the review explores the current developments in real-time nitrate sensors and discusses the challenges of real-time implementation.

The Fabrication of a La2Sn2O7/f-HNT Composite for Non-Enzymatic Electrochemical Detection of 3-Nitro-l-tyrosine in Biological Samples.

Reactive oxygen and nitrogen species (RONS), including 3-nitro-l-tyrosine, play a dual role in human health, inducing oxidative damage and regulating cellular functions. Early and accurate detection of such molecules, such as L-tyrosine in urine, can serve as critical biomarkers for various cancers. In this study, we aimed to enhance the electrochemical detection of these molecules through the synthesis of La2Sn2O7/f-HNT nanocomposites via a simple hydrothermal method. Detailed structural and morphological characterizations confirmed successful synthesis, consistent with our expected outcomes. The synthesized nanocomposites were utilized as nanocatalysts in electrochemical sensors, showing a notable limit of the detection of 0.012 µM for the real-time detection of 3-nitro-l-tyrosine. These findings underscore the potential of nanomaterial-based sensors in advancing early disease detection with high sensitivity, furthering our understanding of cellular oxidative processes.

Pharma's Bio-AI revolution.

Drug development has become unbearably slow and expensive. A key underlying problem is the clinical prediction challenge: the inability to predict which drug candidates will be safe in the human body and for whom. Recently, a dramatic regulatory change has removed FDA's mandated reliance on antiquated, ineffective animal studies. A new frontier is an integration of several disruptive technologies [machine learning (ML), patient-on-chip, real-time sensing, and stem cells], which when integrated, have the potential to address this challenge, drastically cutting the time and cost of developing drugs, and tailoring them to individual patients.

Ultra-wide, attomolar-level limit detection of CD44 biomarker with a silanized optical fiber biosensor.

Measuring cancer biomarkers at ultralow detection limit and high sensitivity could be a promising tool for early diagnosis, monitoring treatment and post-treatment recurrence. Soluble CD44 is a promising diagnostic and prognostic biomarker in several types of cancer including gastric, colon and breast cancer. Several highly sensitive biosensors have been built to measure this important biomarker. However, they did not reach attomolar level of detection. The aim of this work was to build a biosensor capable of detecting CD44 concentrations down to attomolar (aM) level while measuring it in a wide concentration range. Herein, we demonstrate a biosensor that offers 4 key advantages over existing platforms for CD44 detection: 1) detection of CD44 was carried out in a diluted serum down to attomolar level (4.68 aM) which is about 6 orders of magnitude lower than that of a traditional ELISA; 2) fabrication of the sensor is done in a fast way using inexpensive materials making it a disposable fiber optic biosensor; 3) detection of CD44 was performed in a wide dynamic range previously not shown in other similar biosensors; 4) a proof-of-concept experiment was performed using the biosensor to embed it in a catheter to measure the protein in flow conditions.

Real-Time Sensing with Multiplexed Optomechanical Resonators.

Nanoelectromechanical resonators have been successfully used for a variety of sensing applications. Their extreme resolution comes from their small size, which strongly limits their capture area. This leads to a long analysis time and the requirement for large sample quantity. Moreover, the efficiency of the electrical transductions commonly used for silicon resonators degrades with increasing frequency, limiting the achievable mechanical bandwidth and throughput. Multiplexing a large number of high-frequency resonators appears to be a solution, but this is complex with electrical transductions. We propose here a route to solve these issues, with a multiplexing scheme for very high-frequency optomechanical resonators. We demonstrate the simultaneous frequency measurement of three silicon microdisks fabricated with a 200 mm wafer large-scale process. The readout architecture is simple and does not degrade the sensing resolutions. This paves the way toward the realization of sensors for multiparametric analysis with an extremely low limit of detection and response time.

Real-Time Sensing of Output Polymer Flow Temperature and Volumetric Flowrate in Fused Filament Fabrication Process.

In this paper we addressed key challenges in engineering an instrumentation system for sensing and signal processing for real-time estimation of two main process variables in the Fused-Filament-Fabrication process: (i) temperature of the polymer melt exiting the nozzle using a thermocouple; and (ii) polymer flowrate using extrusion width measurements in real-time, in-situ, using a microscope camera. We used a design of experiments approach to develop response surface models for two materials that enable accurate estimation of the polymer exit temperature as a function of polymer flowrate and liquefier temperature with a fit of R2=99.96% and 99.39%. The live video stream of the deposition process was used to compute the flowrate based on a road geometry model. Specifically, a robust extrusion width recognizer REXR algorithm was developed to identify edges of the deposited road and for real-time computation of extrusion width, which was found to be robust to filament colors and materials. The extrusion width measurement was found to be within 0.08 mm of caliper measurements with an R2 value of 99.91% and was found to closely track the requested flowrate from the slicer. This opens new avenues for advancing the engineering science for process monitoring and control of FFF.

Continuous monitoring of molecular biomarkers in microfluidic devices.

The ability to monitor molecular targets is crucial in fields ranging from healthcare to industrial processing to environmental protection. Devices employing biomolecules to achieve this goal are called biosensors. Over the last half century researchers have developed dozens of different biosensor approaches. In this chapter we analyze recent advances in the biosensing field aiming at adapting these to the problem of continuous molecular monitoring in complex sample streams, and how the merging of these sensors with lab-on-a-chip technologies would be beneficial to both. To do so we discuss (1) the components that comprise a biosensor, (2) the challenges associated with continuous molecular monitoring in complex sample streams, (3) how different sensing strategies deal with (or fail to deal with) these challenges, and (4) the implementation of these technologies into lab-on-a-chip architectures.

Image Sensors for Wave Monitoring in Shore Protection: Characterization through a Machine Learning Algorithm.

Waves propagating on the water surface can be considered as propagating in a dispersive medium, where gravity and surface tension at the air-water interface act as restoring forces. The velocity at which energy is transported in water waves is defined by the group velocity. The paper reports the use of video-camera observations to study the impact of water waves on an urban shore. The video-monitoring system consists of two separate cameras equipped with progressive RGB CMOS sensors that allow 1080p HDTV video recording. The sensing system delivers video signals that are processed by a machine learning technique. The scope of the research is to identify features of water waves that cannot be normally observed. First, a conventional modelling was performed using data delivered by image sensors together with additional data such as temperature, and wind speed, measured with dedicated sensors. Stealth waves are detected, as are the inverting phenomena encompassed in waves. This latter phenomenon can be detected only through machine learning. This double approach allows us to prevent extreme events that can take place in offshore and onshore areas.

CHO cell dysfunction due to radiation-induced bystander signals observed by real-time electrical impedance measurement.

Radiation-induced bystander effects (RIBE) have raised many concerns about radiation safety and protection. In RIBE, unirradiated cells receive signals from irradiated cells and exhibit irradiation effects. Until now, most RIBE studies have been based on morphological and biochemical characterization. However, research on the impact of RIBE on biophysical properties of cells has been lagging. Non-invasive indium tin oxide (ITO)-based impedance systems have been used as bioimpedance sensors for monitoring cell behaviors. This powerful technique has not been applied to RIBE research. In this work, we employed an electrical cell-ITO substrate impedance system (ECIIS) to study the RIBE on Chinese hamster ovary (CHO) cells. The bioimpedance of bystander CHO cells (BCHO), alpha(α)-particle (Am-241) irradiated CHO (ICHO), and untreated/unirradiated CHO (UCHO) cells were monitored with a sampling interval of 8 s over a period of 24 h. Media from ICHO cells exposed to different radiation doses (0.3 nGy, 0.5 nGy, and 0.7 nGy) were used to investigate the radiation dose dependence of BCHO cells' impedance. In parallel, we imaged the cells at times where impedance changes were observed. By analyzing the changes in absolute impedance and cell size/cell number with time, we observed that BCHO cells mimicked ICHO cells in terms of modification in cell morphology and proliferation rate. Furthermore, these effects appeared to be time-dependent and inversely proportional to the radiation dose. Hence, this approach allows a label-free study of cellular responses to RIBE with high sensitivity and temporal resolution and can provide crucial insights into the RIBE mechanism.

Rapid and cost-effective nutrient content analysis of cotton leaves using near-infrared spectroscopy (NIRS).

The development of portable near-infrared spectroscopy (NIRS) combined with smartphone cloud-based chemometrics has increased the power of these devices to provide real-time in-situ crop nutrient analysis. This capability provides the opportunity to address nutrient deficiencies early to optimise yield. The agriculture sector currently relies on results delivered via laboratory analysis. This involves the collection and preparation of leaf or soil samples during the growing season that are time-consuming and costly. This delays farmers from addressing deficiencies by several weeks which impacts yield potential; hence, requires a faster solution. This study evaluated the feasibility of using NIRS in estimating different macro- and micronutrients in cotton leaf tissues, assessing the accuracy of a portable handheld NIR spectrometer (wavelength range of 1,350-2,500 nm). This study first evaluated the ability of NIRS to predict leaf nutrient levels using dried and ground cotton leaf samples. The results showed the high accuracy of NIRS in predicting essential macronutrients (0.76 ≤ R 2 ≤ 0.98 for N, P, K, Ca, Mg and S) and most micronutrients (0.64 ≤ R 2 ≤ 0.81 for Fe, Mn, Cu, Mo, B, Cl and Na). The results showed that the handheld NIR spectrometer is a practical option to accurately measure leaf nutrient concentrations. This research then assessed the possibility of applying NIRS on fresh leaves for potential in-field applications. NIRS was more accurate in estimating cotton leaf nutrients when applied on dried and ground leaf samples. However, the application of NIRS on fresh leaves was still quite accurate. Using fresh leaves, the prediction accuracy was reduced by 19% for macronutrients and 11% for micronutrients, compared to dried and ground samples. This study provides further evidence on the efficacy of using NIRS for field estimations of cotton nutrients in combination with a nutrient decision support tool, with an accuracy of 87.3% for macronutrients and 86.6% for micronutrients. This application would allow farmers to manage nutrients proactively to avoid yield penalties or environmental impacts.

Autonomous, Real-Time Monitoring Electrochemical Aptasensor for Circadian Tracking of Cortisol Hormone in Sub-microliter Volumes of Passively Eluted Human Sweat.

The proposed work involves the development of an autonomous, label-free electrochemical sensor for real-time monitoring of cortisol levels expressed naturally in sub-microliter sweat volumes, for prolonged sensing periods of ∼8 h. Highly specific single-stranded DNA (ssDNA) aptamer is used for affinity capture of cortisol hormone eluted in sweat dynamically. The cortisol present in sweat binds to the aptamer capture probe that changes conformation and modulates electrochemical properties at the electrode-buffer interface, which was studied using dynamic light scattering studies for the entire physiological sweat pH. Attenuated total reflectance-Fourier transform infrared spectroscopy and UV-vis spectroscopy were used to optimize the binding chemistry of the elements of the sensor stack. Nonfaradaic electrochemical impedance spectroscopy was used to calibrate the sensor for a dynamic range of 1-256 ng/mL. An R2 of 0.97 with an output signal range of 20-50% was obtained. Dynamic cortisol level variation tracking was studied using continuous dosing experiments to calibrate the sensor for temporal variation. The sensor did not show significant susceptibility to noise due to cross-reactive interferents and nonspecific buffer constituents. The performance of the developed aptasensor was compared with the previously established cortisol immunosensor in terms of surface charge behavior and nonfaradaic biosensing. The aptamer sensor shows a higher signal-to-noise ratio, better resolution, and has a larger output range for the same input range as the cortisol immunosensor. The feasibility of deploying the developed aptasensing scheme as continuous lifestyle and performance monitors was validated through human subject studies.

High-performance SERS detection of pesticides using BiOCl-BiOBr@Pt/Au hybrid nanostructures on styrofoams as 3D functional substrate.

A 3D flexible domestic waste styrofoam is reported as a surface enhanced Raman scattering (SERS) substrate loaded with BiOCl-BiOBr@Pt/Au semiconductor-plasmonic composites. The hydrothermally prepared BiOCl-BiOBr nanocomposite is thoroughly characterized for its crystal structure using X-Ray diffraction, morphology through scanning electron microscopy, and electronic states of the elements using X-ray photoelectron spectroscopy. The alpha cypermethrin (ACM) is chosen as a model pesticide analyte for SERS investigation. The BiOCl-BiOBr@Pt/Au loaded foam substrate exhibited a high enhancement factor (106) and low limit of detection (10-10 M) upon SERS investigation. The unique architecture of the semiconductor-plasmonic composite enables an efficient charge transfer capability and plasmonic hotspots which aids in the enhancement of target analytes. In order to better demonstrate the versatility towards other pesticides, SERS detection of glyphosate and paraquat pesticides are also performed using the fabricated SERS substrate. The stability of the substrate has been investigated in detail for 30 days and the substrate was highly stable. The BiOCl-BiOBr@Pt/Au-based foam substrate also performed well in rapid real-time sensing of alpha cypermethrin on the kiwi fruit exocarp at lower level concentrations. Graphical abstract.

A wearable sensor for the detection of sodium and potassium in human sweat during exercise.

The SwEatch platform, a wearable sensor for sampling and measuring the concentration of electrolytes in human sweat in real time, has been improved in order to allow the sensing of two analytes. The solid contact ion-sensitive electrodes (ISEs) for the detection of Na+ and K+ have been developed in two alternative formulations, containing either poly(3,4-ethylenedioxythiophene) (PEDOT) or poly(3-octylthiophene-2,5-diyl) (POT) as a conductive polymer transducing component. The solution-processable POT formulation simplifies the fabrication process, and sensor to sensor reproducibility has been improved via partial automation using an Opentron® automated pipetting robot. The resulting electrodes showed good sensitivity (52.4 ± 6.3 mV/decade (PEDOT) and 56.4 ± 2.2 mV/decade (POT) for Na+ ISEs, and 45.7 ± 7.4 mV/decade (PEDOT) and 54.3 ± 1.5 mV/decade (POT) for K+) and excellent selectivity towards potential interferents present in human sweat (H+, Na+, K+, Mg2+, Ca2+). The 3D printed SwEatch platform has been redesigned to incorporate a double, mirrored fluidic unit which is capable of drawing sweat from the skin through passive capillary action and bring it in contact with two independent electrodes. The potentiometric signal generated by the electrodes is measured by an integrated electronics board, digitised and transmitted via Bluetooth to a laptop. The results obtained from on-body trials on athletes during cycling show a relatively small increase in sodium (1.89 mM-2.97 mM) and potassium (3.31 mM-7.25 mM) concentrations during the exercise period of up to 90 min.

Design and Integration of a Wireless Stretchable Multimodal Sensor Network in a Composite Wing.

This article presents the development of a stretchable sensor network with high signal-to-noise ratio and measurement accuracy for real-time distributed sensing and remote monitoring. The described sensor network was designed as an island-and-serpentine type network comprising a grid of sensor "islands" connected by interconnecting "serpentines." A novel high-yield manufacturing process was developed to fabricate networks on recyclable 4-inch wafers at a low cost. The resulting stretched sensor network has 17 distributed and functionalized sensing nodes with low tolerance and high resolution. The sensor network includes Piezoelectric (PZT), Strain Gauge (SG), and Resistive Temperature Detector (RTD) sensors. The design and development of a flexible frame with signal conditioning, data acquisition, and wireless data transmission electronics for the stretchable sensor network are also presented. The primary purpose of the frame subsystem is to convert sensor signals into meaningful data, which are displayed in real-time for an end-user to view and analyze. The challenges and demonstrated successes in developing this new system are demonstrated, including (a) developing separate signal conditioning circuitry and components for all three sensor types (b) enabling simultaneous sampling for PZT sensors for impact detection and (c) configuration of firmware/software for correct system operation. The network was expanded with an in-house developed automated stretch machine to expand it to cover the desired area. The released and stretched network was laminated into an aerospace composite wing with edge-mount electronics for signal conditioning, processing, power, and wireless communication.

Strong acid-assisted preparation of green-emissive carbon dots for fluorometric imaging of pH variation in living cells.

New green-emissive carbon dots (G-CDs) are described here and shown to be viable fluorescent nanoprobes for the detection of changes in cellular pH values. By using m-phenylenediamine as the carbon source, G-CDs with an absolute quantum yield of 36% were solvothermally synthesized in the presence of strong H2SO4. The G-CDs have an average size of 2.3 nm and display strong fluorescence with excitation/emission peaks at 450/510 nm. The fluorescence intensity depends on the pH value in the range from 6.0 to 10.0, affording the capability for sensitive detection of intracellular pH variation. The nanosensor with excellent photostability exhibited good fluorescence reversibility in different pH solutions, and showed excellent stability against the influence of other biological species. The nanoprobe was successfully used in confocal fluorescence microscopy to determine pH values in SMMC-7721 cells. Graphical abstract Schematic presentation of green-emissive carbon dots (G-CDs) synthesized using m-phenylenediamine and sufuric acid through a solvothermal method for real-time fluorometric monitoring of intracellular pH values. Mechanism can be ascribed to PET process from the electron lone pair in amino group to the CDs.