Biosensors, Volume 14, Issue 5 (May 2024) – 18 articles

At the heart of the non-implantable electronic revolution lies ionogels, which are remarkably conductive, thermally stable, and even antimicrobial materials. Yet, their potential has been hindered by poor mechanical properties. Herein, a double network (DN) ionogel crafted from 1-Ethyl-3-methylimidazolium chloride ([Emim]Cl), acrylamide (AM), and polyvinyl alcohol (PVA) was constructed. Tensile strength, fracture elongation, and conductivity can be adjusted across a wide range, enabling researchers to fabricate the material to meet specific needs. With adjustable mechanical properties, such as tensile strength (0.06–5.30 MPa) and fracture elongation (363–1373%), this ionogel possesses both robustness and flexibility. This ionogel exhibits a bi-modal response to temperature and strain, making it an ideal candidate for strain sensor applications. It also functions as a flexible strain sensor that can detect physiological signals in real time, opening doors to personalized health monitoring and disease management. Moreover, these gels’ ability to decode the intricate movements of sign language paves the way for improved communication accessibility for the deaf and hard-of-hearing community. This DN ionogel lays the foundation for a future in which e-skins and wearable sensors will seamlessly integrate into our lives, revolutionizing healthcare, human–machine interaction, and beyond. Full article

This manuscript reports the application of sensors for water use efficiency with a focus on the application of an in vivo OECT biosensor. In two distinct experimental trials, the in vivo sensor bioristor was applied in yellow kiwi plants to monitor, in real-time and continuously, the changes in the composition and concentration of the plant sap in an open field during plant growth and development. The bioristor response and physiological data, together with other fruit sensor monitoring data, were acquired and combined in both trials, giving a complete picture of the biosphere conditions. A high correlation was observed between the bioristor index (ΔI_gs), the canopy cover expressed as the fraction of intercepted PAR (fi_PAR), and the soil water content (SWC). In addition, the bioristor was confirmed to be a good proxy for the occurrence of drought in kiwi plants; in fact, a period of drought stress was identified within the month of July. A novelty of the bioristor measurements was their ability to detect in advance the occurrence of defoliation, thereby reducing yield and quality losses. A plant-based irrigation protocol can be achieved and tailored based on real plant needs, increasing water use sustainability and preserving high-quality standards. Full article

Organ-on-a-chip (OOC) is an emerging technology that simulates an artificial organ within a microfluidic cell culture chip. Current cell biology research focuses on in vitro cell cultures due to various limitations of in vivo testing. Unfortunately, in-vitro cell culturing fails to provide an accurate microenvironment, and in vivo cell culturing is expensive and has historically been a source of ethical controversy. OOC aims to overcome these shortcomings and provide the best of both in vivo and in vitro cell culture research. The critical component of the OOC design is utilizing microfluidics to ensure a stable concentration gradient, dynamic mechanical stress modeling, and accurate reconstruction of a cellular microenvironment. OOC also has the advantage of complete observation and control of the system, which is impossible to recreate in in-vivo research. Multiple throughputs, channels, membranes, and chambers are constructed in a polydimethylsiloxane (PDMS) array to simulate various organs on a chip. Various experiments can be performed utilizing OOC technology, including drug delivery research and toxicology. Current technological expansions involve multiple organ microenvironments on a single chip, allowing for studying inter-tissue interactions. Other developments in the OOC technology include finding a more suitable material as a replacement for PDMS and minimizing artefactual error and non-translatable differences. Full article

Wastewater pipelines are present everywhere in urban areas. Wastewater is a preferable fuel for renewable electricity generation from microbial fuel cells. Here, we created an integrated microbial fuel cell pipeline (MFCP) that could be connected to wastewater pipelines and work as an organic content biosensor and energy harvesting device at domestic waste-treatment plants. The MFCP used a pipeline-like terracotta-based membrane, which provided structural support for the MFCP. In addition, the anode and cathode were attached to the inside and outside of the terracotta membrane, respectively. Co−MnO₂ was used as a catalyst to improve the performance of the MFCP cathode. The experimental data showed a good linear relationship between wastewater chemical oxygen demand (COD) concentration and the MFCP output voltage in a COD range of 200–1900 mg/L. This result implies the potential of using the MFCP as a sensor to detect the organic content of the wastewater inside the wastewater pipeline. Furthermore, the MFCP can be used as a long-lasting sustainable energy harvester with a maximum power density of 400 mW/m² harvested from 1900 mg/L COD wastewater at 25 °C. Full article

The surfactant cetyltrimethylammonium bromide (CTAB) induces the aggregation of gold nanoclusters (GNCs), leading to the development of a proposed fluorometric technique for detecting thiocyanate (SCN⁻) ions based on an anti-aggregation mechanism. This approach is straightforward to execute, highly sensitive, and selective. A significant quenching effect occurs in fluorescence upon using the aggregation agent CTAB in GNCs synthesis, resulting in a transition from intense red fluorescence to dim red. The decrease in fluorescence intensity of GNCs in the presence of CTAB is caused by the mechanism of fluorescence quenching mediated by aggregation. As the levels of SCN⁻ rise, the fluorescence of CTAB-GNCs increases; this may be detected using spectrofluorometry or by visually inspecting under UV irradiation. The recovery of red fluorescence of CTAB-GNCs in the presence of SCN⁻ enables the precise and discerning identification of SCN⁻ within the concentration range of 2.86–140 nM. The minimum detectable concentration of the SCN⁻ ions was 1 nM. The selectivity of CTAB-GNCs towards SCN⁻ ions was investigated compared to other ions, and it was demonstrated that CTAB-GNCs exhibit exceptional selectivity. Furthermore, we believe that CTAB-GNCs have novel possibilities as favorable sensor candidates for various industrial applications. Our detection technique was validated by analyzing SCN⁻ ions in milk samples, which yielded promising results. Full article

This work presents a novel approach for tailoring molecularly imprinted polymers (MIPs) with a preliminary stage of atom transfer radical polymerization (ATRP), for a more precise definition of the imprinted cavity. A well-defined copolymer of acrylamide and N,N′-methylenebisacrylamide (PAAm-co-PMBAm) was synthesized by ATRP and applied to gold electrodes with the template, followed by a crosslinking reaction. The template was removed from the polymer matrix by enzymatic/chemical action. The surface modifications were monitored via electrochemical impedance spectroscopy (EIS), having the MIP polymer as a non-conducting film designed with affinity sites for CA15-3. The resulting biosensor exhibited a linear response to CA15-3 log concentrations from 0.001 to 100 U/mL in PBS or in diluted fetal bovine serum (1000×) in PBS. Compared to the polyacrylamide (PAAm) MIP from conventional free-radical polymerization, the ATRP-based MIP extended the biosensor’s dynamic linear range 10-fold, improving low concentration detection, and enhanced the signal reproducibility across units. The biosensor demonstrated good sensitivity and selectivity. Overall, the work described confirmed that the process of radical polymerization to build an MIP material influences the detection capacity for the target substance and the reproducibility among different biosensor units. Extending this approach to other cancer biomarkers, the methodology presented could open doors to a new generation of MIP-based biosensors for point-of-care disease diagnosis. Full article

Microwave radiometry (MWR) is instrumental in detecting thermal variations in skin tissue before anatomical changes occur, proving particularly beneficial in the early diagnosis of cancer and inflammation. This study concisely traces the evolution of microwave radiometers within the medical sector. By analyzing a plethora of pertinent studies and contrasting their strengths, weaknesses, and performance metrics, this research identifies the primary factors limiting temperature measurement accuracy. The review establishes the critical technologies necessary to overcome these limitations, examines the current state and prospective advancements of each technology, and proposes comprehensive implementation strategies. The discussion elucidates that the precise measurement of human surface and subcutaneous tissue temperatures using an MWR system is a complex challenge, necessitating an integration of antenna directionality for temperature measurement, radiometer error correction, hardware configuration, and the calibration and precision of a multilayer tissue forward and inversion method. This study delves into the pivotal technologies for non-invasive human tissue temperature monitoring in the microwave frequency range, offering an effective approach for the precise assessment of human epidermal and subcutaneous temperatures, and develops a non-contact microwave protocol for gauging subcutaneous tissue temperature distribution. It is anticipated that mass-produced measurement systems will deliver substantial economic and societal benefits. Full article

Detecting low concentrations of biomarkers is essential in clinical laboratories. To improve analytical sensitivity, especially in identifying fluorescently labeled molecules, typical optical detection systems, consisting of a photodetector or camera, utilize time-resolved measurements. Taking a different approach, magnetic modulation biosensing (MMB) is a novel technology that combines fluorescently labeled probes and magnetic particles to create a sandwich assay with the target molecules. By concentrating the target molecules and then using time-resolved measurements, MMB provides the rapid and highly sensitive detection of various biomarkers. Here, we propose a novel signal-processing algorithm that enhances the detection and estimation of target molecules at low concentrations. By incorporating both temporally and spatially resolved measurements using human interleukin-8 as a target molecule, we show that the new algorithm provides a 2–4-fold improvement in the limit of detection and an ~25% gain in quantitative resolution. Full article

Zebrafish larvae have emerged as a valuable model for studying heart physiology and pathophysiology, as well as for drug discovery, in part thanks to its transparency, which simplifies microscopy. However, in fluorescence-based optical mapping, the beating of the heart results in motion artifacts. Two approaches have been employed to eliminate heart motion during calcium or voltage mapping in zebrafish larvae: the knockdown of cardiac troponin T2A and the use of myosin inhibitors. However, these methods disrupt the mechano-electric and mechano-mechanic coupling mechanisms. We have used ratiometric genetically encoded biosensors to image calcium in the beating heart of intact zebrafish larvae because ratiometric quantification corrects for motion artifacts. In this study, we found that halting heart motion by genetic means (injection of tnnt2a morpholino) or chemical tools (incubation with para-aminoblebbistatin) leads to bradycardia, and increases calcium levels and the size of the calcium transients, likely by abolishing a feedback mechanism that connects contraction with calcium regulation. These outcomes were not influenced by the calcium-binding domain of the gene-encoded biosensors employed, as biosensors with a modified troponin C (Twitch-4), calmodulin (mCyRFP1-GCaMP6f), or the photoprotein aequorin (GFP-aequorin) all yielded similar results. Cardiac contraction appears to be an important regulator of systolic and diastolic Ca²⁺ levels, and of the heart rate. Full article

Antimicrobial resistance (AMR) has become a crucial global health issue. Antibiotic-resistant bacteria can survive after antibiotic treatments, lowering drug efficacy and increasing lethal risks. A microfluidic water-in-oil emulsion droplet system can entrap microorganisms and antibiotics within the tiny bioreactor, separate from the surroundings, enabling independent assays that can be performed in a high-throughput manner. This study presents the development of a label-free dielectrophoresis (DEP)-based microfluidic platform to sort droplets that co-encapsulate Escherichia coli (E. coli) and ampicillin (Amp) and droplets that co-encapsulate Amp-resistant (AmpR) E. coli with Amp only based on the conductivity-dependent DEP force (F_DEP) without the assistance of optical analyses. The 9.4% low conductivity (LC) Luria–Bertani (LB) broth diluted with 170 mM mannitol can maintain E. coli and AmpR E. coli growth for 3 h and allow Amp to kill almost all E. coli, which can significantly increase the LCLB conductivity by about 100 μS/cm. Therefore, the AmpR E. coli/9.4%LCLB/Amp where no cells are killed and the E. coli/9.4%LCLB/Amp-containing droplets where most of the cells are killed can be sorted based on this conductivity difference at an applied electric field of 2 MHz and 100 V_pp that generates positive F_DEP. Moreover, the sorting ratio significantly decreased to about 50% when the population of AmpR E. coli was equal to or higher than 50% in droplets. The conductivity-dependent DEP-based sorting platform exhibits promising potential to probe the ratio of AmpR E. coli in an unknown bacterial sample by using the sorting ratio as an index. Full article

Magnetic Induction Tomography (MIT) is a non-invasive imaging technique used for dynamic monitoring and early screening of cerebral hemorrhage. Currently, there is a significant challenge in cerebral hemorrhage MIT due to weak detection signals, which seriously affects the accuracy of the detection results. To address this issue, a dual-plane enhanced coil was proposed by combining the target field method with consideration of the spatial magnetic field attenuation pattern within the imaging target region. Simulated detection models were constructed using the proposed coil and cylindrical coil as excitation coils, respectively, and simulation imaging tests were conducted using the detection results. The simulation results indicate that compared to the cylindrical coil, the proposed coil enhances the linearity of the magnetic field within the imaging target region by 60.43%. Additionally, it effectively enhances the detection voltage and phase values. The simulation results of hemorrhage detection show that the proposed coil improves the accuracy of hemorrhage detection by 18.26%. It provides more precise detection results, offering a more reliable solution for cerebral hemorrhage localization and detection. Full article

This study presents a biosensor fabricated based on integrated passive device (IPD) technology to measure microbial growth on solid media in real-time. Yeast (Pichia pastoris, strain GS115) is used as a model organism to demonstrate biosensor performance. The biosensor comprises an interdigital capacitor in the center with a helical inductive structure surrounding it. Additionally, 12 air bridges are added to the capacitor to increase the strength of the electric field radiated by the biosensor at the same height. Feasibility is verified by using a capacitive biosensor, and the change in capacitance values during the capacitance detection process with the growth of yeast indicates that the growth of yeast can induce changes in electrical parameters. The proposed IPD-based biosensor is used to measure yeast drop-added on a 3 mm medium for 100 h at an operating frequency of 1.84 GHz. The resonant amplitude of the biosensor varies continuously from 24 to 72 h due to the change in colony height during vertical growth of the yeast, with a maximum change of 0.21 dB. The overall measurement results also fit well with the Gompertz curve. The change in resonant amplitude between 24 and 72 h is then analyzed and reveals a linear relationship with time with a coefficient of determination of 0.9844, indicating that the biosensor is suitable for monitoring yeast growth. Thus, the proposed biosensor is proved to have potential in the field of microbial proliferation detection. Full article

Graphene-based materials are actively being investigated as sensing elements for the detection of different analytes. Both graphene grown by chemical vapor deposition (CVD) and graphene oxide (GO) produced by the modified Hummers’ method are actively used in the development of biosensors. The production costs of CVD graphene- and GO-based sensors are similar; however, the question remains regarding the most efficient graphene-based material for the construction of point-of-care diagnostic devices. To this end, in this work, we compare CVD graphene aptasensors with the aptasensors based on reduced GO (rGO) for their capabilities in the detection of NT-proBNP, which serves as the gold standard biomarker for heart failure. Both types of aptasensors were developed using commercial gold interdigitated electrodes (IDEs) with either CVD graphene or GO formed on top as a channel of liquid-gated field-effect transistor (FET), yielding GFET and rGO-FET sensors, respectively. The functional properties of the two types of aptasensors were compared. Both demonstrate good dynamic range from 10 fg/mL to 100 pg/mL. The limit of detection for NT-proBNP in artificial saliva was 100 fg/mL and 1 pg/mL for rGO-FET- and GFET-based aptasensors, respectively. While CVD GFET demonstrates less variations in parameters, higher sensitivity was demonstrated by the rGO-FET due to its higher roughness and larger bandgap. The demonstrated low cost and scalability of technology for both types of graphene-based aptasensors may be applicable for the development of different graphene-based biosensors for rapid, stable, on-site, and highly sensitive detection of diverse biochemical markers. Full article

Electrochemical biosensors include a recognition component and an electronic transducer, which detect the body fluids with a high degree of accuracy. More importantly, they generate timely readings of the related physiological parameters, and they are suitable for integration into portable, wearable and implantable devices that are significant relative to point-of-care diagnostics scenarios. As an example, the personal glucose meter fundamentally improves the management of diabetes in the comfort of the patients’ homes. This review paper analyzes the principles of electrochemical biosensing and the structural features of electrochemical biosensors relative to the implementation of health monitoring and disease diagnostics strategies. The analysis particularly considers the integration of the biosensors into wearable, portable, and implantable systems. The fundamental aim of this paper is to present and critically evaluate the identified significant developments in the scope of electrochemical biosensing for preventive and customized point-of-care diagnostic devices. The paper also approaches the most important engineering challenges that should be addressed in order to improve the sensing accuracy, and enable multiplexing and one-step processes, which mediate the integration of electrochemical biosensing devices into digital healthcare scenarios. Full article

The Wearable Robotic Limb (WRL) is a type of robotic arm worn on the human body, aiming to enhance the wearer’s operational capabilities. However, proposing additional methods to control and perceive the WRL when human limbs are heavily occupied with primary tasks presents a challenge. Existing interactive methods, such as voice, gaze, and electromyography (EMG), have limitations in control precision and convenience. To address this, we have developed an interactive device that utilizes the mouth and tongue. This device is lightweight and compact, allowing wearers to achieve continuous motion and contact force control of the WRL. By using a tongue controller and mouth gas pressure sensor, wearers can control the WRL while also receiving sensitive contact feedback through changes in mouth pressure. To facilitate bidirectional interaction between the wearer and the WRL, we have devised an algorithm that divides WRL control into motion and force-position hybrid modes. In order to evaluate the performance of the device, we conducted an experiment with ten participants tasked with completing a pin-hole assembly task with the assistance of the WRL system. The results show that the device enables continuous control of the position and contact force of the WRL, with users perceiving feedback through mouth airflow resistance. However, the experiment also revealed some shortcomings of the device, including user fatigue and its impact on breathing. After experimental investigation, it was observed that fatigue levels can decrease with training. Experimental studies have revealed that fatigue levels can decrease with training. Furthermore, the limitations of the device have shown potential for improvement through structural enhancements. Overall, our mouth and tongue interactive device shows promising potential in controlling the WRL during tasks where human limbs are occupied. Full article

Combinatorial drug therapy has emerged as a critically important strategy in medical research and patient treatment and involves the use of multiple drugs in concert to achieve a synergistic effect. This approach can enhance therapeutic efficacy while simultaneously mitigating adverse side effects. However, the process of identifying optimal drug combinations, including their compositions and dosages, is often a complex, costly, and time-intensive endeavor. To surmount these hurdles, we propose a novel microfluidic device capable of simultaneously generating multiple drug concentration gradients across an interlinked array of culture chambers. This innovative setup allows for the real-time monitoring of live cell responses. With minimal effort, researchers can now explore the concentration-dependent effects of single-agent and combination drug therapies. Taking neural stem cells (NSCs) as a case study, we examined the impacts of various growth factors—epithelial growth factor (EGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF)—on the differentiation of NSCs. Our findings indicate that an overdose of any single growth factor leads to an upsurge in the proportion of differentiated NSCs. Interestingly, the regulatory effects of these growth factors can be modulated by the introduction of additional growth factors, whether singly or in combination. Notably, a reduced concentration of these additional factors resulted in a decreased number of differentiated NSCs. Our results affirm that the successful application of this microfluidic device for the generation of multi-drug concentration gradients has substantial potential to revolutionize drug combination screening. This advancement promises to streamline the process and accelerate the discovery of effective therapeutic drug combinations. Full article

Brain–computer interface (BCI) for motor imagery is an advanced technology used in the field of medical rehabilitation. However, due to the poor accuracy of electroencephalogram feature classification, BCI systems often misrecognize user commands. Although many state-of-the-art feature selection methods aim to enhance classification accuracy, they usually overlook the interrelationships between individual features, indirectly impacting the accuracy of feature classification. To overcome this issue, we propose an adaptive feature learning model that employs a Riemannian geometric approach to generate a feature matrix from electroencephalogram signals, serving as the model’s input. By integrating the enhanced adaptive L1 penalty and weighted fusion penalty into the sparse learning model, we select the most informative features from the matrix. Specifically, we measure the importance of features using mutual information and introduce an adaptive weight construction strategy to penalize regression coefficients corresponding to each variable adaptively. Moreover, the weighted fusion penalty balances weight differences among correlated variables, reducing the model’s overreliance on specific variables and enhancing accuracy. The performance of the proposed method was validated on BCI Competition IV datasets IIa and IIb using the support vector machine. Experimental results demonstrate the effectiveness and superiority of the proposed model compared to the existing models. Full article

The rapid and sensitive detection of pathogenic bacteria is becoming increasingly important for the timely prevention of contamination and the treatment of infections. Biosensors based on nucleic acid aptamers, integrated with optical, electrochemical, and mass-sensitive analytical techniques, have garnered intense interest because of their versatility, cost-efficiency, and ability to exhibit high affinity and specificity in binding bacterial biomarkers, toxins, and whole cells. This review highlights the development of aptamers, their structural characterization, and the chemical modifications enabling optimized recognition properties and enhanced stability in complex biological matrices. Furthermore, recent examples of aptasensors for the detection of bacterial cells, biomarkers, and toxins are discussed. Finally, we explore the barriers to and discuss perspectives on the application of aptamer-based bacterial detection. Full article