Flexible Biosensor Research Articles

System-on-Board Integrated Flexible OEGFET Aptasensor for Multianalyte Testing in Saliva

The need for oral health monitoring Point of Care (PoC) systems is ever growing. We have recently reported a novel, aptamer-based flexible biosensor for detection of a high impact hormone – cortisol – in saliva samples using organic electrolyte gated FET (OEGFET) technology. In this work, we are reporting a system-on-board level integration of an improved flexible OEGFET aptasensor which was previously reliant on a bench-top measurement set-up. The reported flexible OEGFET aptasensor has integrated soft microfluidics and a low power (< 300mW) customized printed circuit board. The interfacing of flexible aptasensor to the circuit board was achieved using a low-temperature extrusion printing technique. The system was assessed using spiked saliva supernatants which established comparable detection threshold for the miniaturized, board-based configuration. In this expanded paper, we furthermore demonstrate improvements to device structure and the integration process which improves signal to noise resolution. By implementing 3D printing technology, the interconnects between the flexible sensor and conventional PCB are more durable and possess better conductivity. The optimized transistor pattern allows for multiple analytes to be tested concurrently. Side-by-side analysis of a device that is specific to cortisol biomolecules and a non-specific device shows the system-on-board is capable of distinguishing between binding and non-binding device behavior. The portable oral biosensor has the potential to be transformed into a multianalyte sensing platform and is therefore a promising prototype for future clinical validation.

In situ generated PANI promoted flexible photoelectrochemical biosensor for ochratoxin A based on GOx-stuffed DNA hydrogel as enhancer

Aflexible photoelectrochemical (PEC) biosensor isproposed for the sensitive detection of ochratoxin A (OTA) based on glucose oxidase (GOx)-encapsulated target-responsive hydrogel, using Fenton reaction-mediated in situ formation of polyaniline (PANI) as signal amplified strategy. The target-responsive DNA hydrogels with high loading capacity can carry a large amount of GOx, which not only avoids laborious labeling process but also enhances the analytical performance. Upon introduction of target molecules, the hydrogel can be opened, and multiple GOx was released, thus producing lots of H2O2 via catalytic reduction of glucose. As a component of the Fenton reagent, H2O2 can react with the Fe2+ on the graphene oxidase-PAMAM-Fe2+ (GO-PAMAM-Fe2+) to generate Fe3+ and ·OH. This in turn can oxidize aniline and generate polyaniline (PANI), resulting in the enhancement of the photocurrent signal of GO-MoS2-CdS photoelectrode. The GO-PAMAM-Fe2+ as the neighborhood component of GO-MoS2-CdS-based photoactive material not only can increase the loading amount of Fe2+, but also can inhibit the decrease of photocurrent of GO-MoS2-CdS by direct modification of Fe2+ on the photoactive material. Moreover, the high loading capacity of DNA hydrogel can efficiently promote the performance of the PEC biosensor. The PEC biosensor exhibited satisfactory analytical performance for OTA with a linear range of 0.0001-0.1ng/mL and a low detection limit of 0.05pg/mL. Itpresents recommendable specificity, stability, and practical applications. Importantly, the PEC biosensor provides a new concept for construction of PEC biosensing platform.

One-step laser synthesis platinum nanostructured 3D porous graphene: A flexible dual-functional electrochemical biosensor for glucose and pH detection in human perspiration

There has been a recent increase in the demand for wearable sensors for sweat glucose monitoring to facilitate diabetes management in a patient-friendly and non-invasive manner. To address this issue, the key challenge lies in the design of flexible sensors with high conductivity, miniaturized patterning, and environmental friendliness. Herein, we introduce a flexible electrochemical sensing system for glucose and pH detection based on one-step laser-scribed PtNPs nanostructured 3D porous laser-scribed graphene (LSG). The as-prepared nanocomposites can synchronously possess hierarchical porous graphene architectures, whereas PtNPs can significantly enhance their sensitivity and electrocatalytic activity. Benefiting from these advantages, the fabricated Pt-HEC/LSG biosensor exhibited a high sensitivity of 69.64 μA mM−1 cm−2 as well as a low limit of detection (LOD) of 0.23 μM at a detection range of 5–3000 μM (covering the glucose range in sweat). Moreover, the pH sensor was functionalized with polyaniline (PANI) on a Pt-HEC/LSG electrode, and it also exhibited high sensitivity (72.4 mV/pH) in the linear range of pH 4–8. The feasibility of the biosensor was confirmed by analyzing human perspiration during physical exercise. This dual-functional electrochemical biosensor displayed excellent performance, including a low detection limit, high selectivity, and great flexibility. These results confirm that the proposed dual-functional flexible electrode and fabrication process are highly promising for application in human sweat-based electrochemical glucose and pH sensors.

Flexible organic field-effect transistors-based biosensors: progress and perspectives.

Organic field-effect transistors (OFETs) have been proposed beyond three decades while becoming a research hotspot again in recent years because of the fast development of flexible electronics. Many novel flexible OFETs-based devices have been reported in these years. Among these devices, flexible OFETs-based sensors made great strides because of the extraordinary sensing capability of FET. Most of these flexible OFETs-based sensors were designed for biological applications due to the advantages of flexibility, reduced complexity, and lightweight. This paper reviews the materials, fabrications, and applications of flexible OFETs-based biosensors. Besides, the challenges and opportunities of the flexible OFETs-based biosensors are also discussed.

Wearable Localized Surface Plasmon Resonance-Based Biosensor with Highly Sensitive and Direct Detection of Cortisol in Human Sweat

Wearable biosensors have the potential for developing individualized health evaluation and detection systems owing to their ability to provide continuous real-time physiological data. Among various wearable biosensors, localized surface plasmon resonance (LSPR)-based wearable sensors can be versatile in various practical applications owing to their sensitive interactions with specific analytes. Understanding and analyzing endocrine responses to stress is particularly crucial for evaluating human performance, diagnosing stress-related diseases, and monitoring mental health, as stress takes a serious toll on physiological health and psychological well-being. Cortisol is an essential biomarker of stress because of the close relationship between cortisol concentration in the human body and stress level. In this study, a flexible LSPR biosensor was manufactured to detect cortisol levels in the human body by depositing gold nanoparticle (AuNP) layers on a 3-aminopropyltriethoxysilane (APTES)-functionalized poly (dimethylsiloxane) (PDMS) substrate. Subsequently, an aptamer was immobilized on the surface of the LSPR substrate, enabling highly sensitive and selective cortisol capture owing to its specific cortisol recognition. The biosensor exhibited excellent detection ability in cortisol solutions of various concentrations ranging from 0.1 to 1000 nM with a detection limit of 0.1 nM. The flexible LSPR biosensor also demonstrated good stability under various mechanical deformations. Furthermore, the cortisol levels of the flexible LSPR biosensor were also measured in the human epidermis before and after exercise as well as in the morning and afternoon. Our biosensors, which combine easily manufactured flexible sensors with sensitive cortisol-detecting molecules to measure human stress levels, could be versatile candidates for human-friendly products.

Computational Investigation of Chirality-Based Separation of Carbon Nanotubes Using Tripeptide Library

Carbon nanotubes (CNT) have fascinating applications in flexible electronics, biosensors, and energy storage devices, and are classified as metallic or semiconducting based on their chirality. Semiconducting CNTs have been teased as a new material for building blocks in electronic devices, owing to their band gap resembling silicon. However, CNTs must be sorted into metallic and semiconducting for such applications. Formerly, gel chromatography, ultracentrifugation, size exclusion chromatography, and phage display libraries were utilized for sorting CNTs. Nevertheless, these techniques are either expensive or have poor efficiency. In this study, we utilize a novel technique of using a library of nine tripeptides with glycine as a central residue to study the effect of flanking residues for large-scale separation of CNTs. Through molecular dynamics, we found that the tripeptide combinations with threonine as one of the flanking residues have a high affinity for metallic CNTs, whereas those with flanking residues having uncharged and negatively charged polar groups show selectivity towards semiconducting CNTs. Furthermore, the role of interfacial water molecules and the ability of the tripeptides to form hydrogen bonds play a crucial role in sorting the CNTs. It is envisaged that CNTs can be sorted based on their chirality-selective interaction affinity to tripeptides.

Hierarchically self-constructed alignment layer of comb-shaped amphiphilic copolymers for spontaneous and stable vertical orientation of liquid crystals

Hierarchically self-constructed ordered nanoarchitectures for precise control of molecular alignment has received much attention in a wide range of applications from optoelectronic devices to flexible biosensors. Herein, we present a facile and effective fabrication strategy to create a hierarchically constructed self-alignment layer of comb-shaped amphiphilic copolymers for spontaneous vertical molecular orientation of liquid crystals (LCs). Amphiphilic poly(vinyl 4-heptylbenzoate)-g-poly(vinyl alcohol) (PVHB-g-PVA) as a comb-shaped copolymer was doped to an LC medium, and its interfacial self-assembly on indium tin oxide electrode induced the hierarchical self-constructed alignment layer through hydrophilic interactions of hydroxy groups. In addition, hydrophobic and cooperative interactions of alkyl phenyl moieties in amphiphilic copolymers ensured the stable vertical self-alignment of LC molecules. Compared to conventional polyimide layer, the proposed self-constructed alignment layer afforded high vertical alignment ability for LCs and outstanding device performance in terms of the threshold voltage and response speed. Furthermore, the long-term alignment reliability of the proposed copolymeric self-assemblies was comparable to that of commercial alignment layer.

Flexible Point-of-Care Electrodes for Ultrasensitive Detection of Bladder Tumor-Relevant miRNA in Urine.

Portable point-of-care testing (POCT) is currently drawing enormous attention owing to its great potential for disease diagnosis and personal health management. Electrochemical biosensors, with the intrinsic advantages of cost-effectiveness, fast response, ease of miniaturization, and integration, are considered as one of the most promising candidates for POCT application. However, the clinical application of electrochemical biosensors-based POCT is hindered by the decreased detection sensitivity due to the low abundance of disease-relevant biomolecules in extremely complex biological samples. Herein, we construct a flexible electrochemical biosensor based on single-stranded DNA functionalized single-walled carbon nanotubes (ssDNA-SWNTs) for high sensitivity and stability detection of miRNA-21 in human urine to achieve bladder cancer (BCa) diagnosis and classification. The ssDNA-SWNT electrodes with a 2D interconnected network structure exhibit a high electrical conductivity, thus enabling the ultrasensitive detection of miRNA-21 with a detection limit of 3.0 fM. Additionally, the intrinsic flexibility of ssDNA-SWNT electrodes endows the biosensors with the capability to achieve high stability detection of miRNA-21 even under large bending deformations. In a cohort of 40 BCa patients at stages I-III and 44 negative control samples, the constructed ssDNA-SWNT biosensors could detect BCa with a 92.5% sensitivity, an 88.6% specificity, and classify the cancer stages with an overall accuracy of 81.0%. Additionally, the flexible ssDNA-SWNT biosensors could also be utilized for treatment efficiency assessment and cancer recurrence monitoring. Owing to their excellent sensitivity and stability, the designed flexible ssDNA-SWNT biosensors in this work propose a strategy to realize point-of-care detection of complex clinical samples to achieve personalized healthcare.

Flexible biosensor based on signal amplification of gold nanoparticles-composite flower clusters for glucose detection in sweat

Flexible non-invasive glucose monitoring sensor addresses the limitations of intermittent detection and provides the opportunity for optimal therapeutic interventions. However, the low sensitivity of non-invasive sensors restricted their wide applications. In this study, a facile and versatile three-dimensional flexible glucose sensor based on nano-material signal amplification through the structural design and surface modification of sensing electrodes was constructed. Tannic acid-3-aminopropyltriethoxysilane (TA-APTES) coatings were prepared on the activated carbon cloth (aCC) via Michael addition and Schiff base reactions, followed by in situ reductions of gold nanoparticles (AuNPs) to yield AuNPs/TA-APTES/aCC electrodes. Subsequently, glucose oxidases (GOx) were immobilized at the surface of AuNPs to form the sensor. The GOx AuNPs/TA-APTES/aCC sensors exhibit high sensitivity, low detection limit, and fast response rate. The advantage of the GOx AuNPs/TA-APTES/aCC sensors is further illustrated by the excellent stability and the performance in sweat samples with complex components. The design concept of the GOx AuNPs/TA-APTES/aCC for flexible biosensors could potentially drive the development of flexible skin-mountable sensors for monitoring glucose in biofluids.

Flexing frontiers: Pioneering advances in biosensors for instant health insights

Biosensors that incorporate a biological recognition element with a transducer offer a rapid, simple approach for selective detection of analytes. However, conventional rigid biosensors have limited capabilities for continuous on-body monitoring applications. The emergence of flexible electronics has opened new possibilities for developing conformal biosensing platforms that can intimately interface with soft, curvilinear surfaces like skin for non-invasive health tracking. This review covers the fundamentals of biosensor technologies and recent progress in flexible biosensors aimed at pointof- care diagnostics and medical monitoring. Key developments in materials, electrochemical sensing interfaces, microfluidics integration and wireless connectivity are highlighted. Examples of flexible biosensors for metabolites, electrolytes, proteins and nucleic acids are presented along with capabilities and limitations. Current challenges include improving biocompatibility, correlation with standard assays, wireless range, manufacturability, and regulatory requirements. Further research on translating flexible biosensor devices from initial proof-of-concepts to validated medical products is warranted. Overall, flexible biosensors hold immense promise to enable continuous personalized health monitoring.

Carbon nanotube based biologically modified field effect transistors (CNT-BioFETs): A research review

In recent years, CNT-BioFETs have attracted great attention because they have been found as ideal biosensor with high selectivity, real-time response and have capability of label free detection. In this article, we present a brief overview of the CNT Field-Effect Transistor-based Biosensors, its working principle and its different types such as ENFET, ImmunoFET, DNA FET and Cell-based FET. The working principle of an n-channel CNT ISFET, the basic block of the BioFET is also discussed in brief. The use of CNT as a conducting channel is evaluated in a few examples of CNT BioFET structures with a detailed view onto its few properties including sensitivity, linear working range and limit of detection. Recent technological advances in the realm of CNT BioFET such as flexible and wearable biosensors are also examined. Keeping in view the above insight, a future prospective is provided later on how to improve the device performance whilst maintaining device miniaturization which is essential in the present More-than-Moore technology-driven world.

Amperometric Measurements by a Novel Aerosol Jet Printed Flexible Sensor for Wearable Applications

In the last years, increasing interest has been addressed on wearable devices for the continuous monitoring of biochemical profiles of patients and athletes. Among various markers, lactate represents one of the most interesting to deepen the knowledge on fatigue processes, in combination with traditional electromyographic features. In this work, we propose a new, low-cost, rapid, and flexible electrochemical amperometric lactate carbon biosensor fabricated by the novel technique of aerosol jet printing (AJP). The developed biosensors were combined with a paper-based microfluidic system and a chitosan-based stable functionalization to allow a long-term continuous monitoring of human daily activities. The sensor performances were evaluated by static and dynamic electrochemical tests in buffered media. The limit of detection is 11 ± 2 mM for the static setup and of 15 ± 6 mM for the dynamic setup, while sensitivity is 0.02 and 0.04 <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\mu \text{A}$ </tex-math></inline-formula> /mM, respectively, with single sigma standard deviation lower than 8%. Increasing and decreasing concentration steps of lactate induces comparable response times below 30 s. These results obtained in vitro under controlled laboratory conditions represent a promising starting point to pursue with ex-vivo and in vivo validation for the future development of stand-alone wearable patches for noninvasive lactate measurements.

Smart sensing flexible sutures for glucose monitoring in house sparrows.

There is a need for flexible chemical sensors for the ecological and physiological research of avian species such as house sparrows (Passer domesticus). Current methods in this field are invasive and require multiple physical interactions with the birds. Emerging research in flexible bioelectronics can enable realization of implantable devices that are mechanically compliant with the underlying tissues for continuous real-time sensing in situ. However, challenges still remain in forming an intimate flexible interface. One of the promising flexible bioelectronic platforms for tissue-embedded sensing is based on functionalizing surgical sutures or threads. Threads have three-dimensional flexibility, high surface-area-to-volume ratio, inherent wicking properties, and are easily functionalizable using reel-to-reel dip coating. Threads are ideal as they are lightweight, therefore, would not interfere with flight motion and would only require minimal interaction with the bird. However, the challenge remains in achieving a highly conductive yet flexible electrode for electrochemical sensing using materials such as gold. In this study, we address this issue through novel gold deposition directly on thread substrate followed by enzyme immobilization to realize flexible electrochemical glucose biosensors on medical-grade sutures. These sensors were calibrated and tested in a range that is wide enough to include the expected range of glucose concentration in house sparrows (0-8.55 mM). Glucose monitoring in house sparrows will provide insights into energy metabolism and regulation during stress responses. In addition, the stability, repeatability, and selectivity of the sensor were tested with final validation in a real bird. Our innovative gold-coated, thread-based flexible electrochemical glucose sensor can also be used in other small and large animals. This can also be extended to monitoring other metabolites in future.

A Potentiometric Enzymatic Flexible Dopamine Biosensor With Temperature Compensation Based on the Flexible Printed Circuit Board

A Potentiometric Enzymatic Flexible Dopamine Biosensor With Temperature Compensation Based on the Flexible Printed Circuit Board

Wearable potentiometric biosensor for analysis of urea in sweat

Herein, we introduce wearable potentiometric biosensors on screen-printed carbon electrodes (SPCEs) for on-body and on-site monitoring of urea in sweat. The biosensor architecture was judiciously designed to detect urea at different pHs and incorporate a pH sensor, thus containing polyaniline ink, urease bioink and a polyvinylchloride membrane. Urea detection could be performed in the wide range from 5 to 200 mM at pH 7.0, encompassing urea levels in human sweat. The biosensor response was fast (incubation time 5 min), with no interference from other substances in sweat. Reliable urea detection could be done in undiluted human sweat with a skin-worn flexible device using the pH correction strategy afforded by the pH sensor. The performance of the epidermal biosensor was not affected by severe bending strains. The feasibility of mass production was demonstrated by fabricating epidermal flexible biosensors using slot-die coating with a roll-to-roll technique.

Flexible enzymatic biosensor based on graphene sponge for glucose detection in human sweat

The development of flexible glucose biosensors makes it possible to perform non-invasive blood glucose monitoring through wearable devices, which is of great significance for the prevention and treatment of diabetes. In this study, a flexible GOx/CTS/GS/PB (GCGP) biosensor for sweat glucose detection was fabricated, which is comprised of gold electrode, Prussian blue (PB), graphene sponge (GS) chitosan (CTS) and glucose oxidase (GOx). The GCGP biosensor realizes a high detection sensitivity of 1790 nA·mM−1·cm−2 and a low detection limit of 2.45 μM (S/N = 3) towards sweat glucose at a low potential (0.075 V, vs. Ag/AgCl) in a linear range from 8.17 to 1000 μM. Moreover, the GCGP biosensor shows high selectivity for glucose and has a good response to glucose in real sweat, which was collected from volunteers playing table tennis. The superior performance of flexible sweat glucose sensors can be due in no small part to the addition of GS. The large specific surface area and the cross-linked hierarchical porous structure of GS enable easy absorption and even distribution of a large amount of GOx. Combined with the high conductivity inherited from graphene, multiple channels for the rapid transport of electrons and ions are available. The abundant binding sites of GS provide the possibility for further composites with other functional materials to improve the performance of the flexible sweat glucose biosensor in future research.

Flexible and printable integrated biosensors for monitoring sweat and skin condition

Wearable and flexible sensors are playing increasing roles in health monitoring (like physiological electrical signals and components of biofluids). Therein, sweat as a carrier of informative biomarkers would attract great attention for health status identification. However, most wearable biosensors have a short lifetime with complex fabrication processes and expensive costs, which would largely limit the application scene to some extent. Here, we developed a state-of-the-art flexible and integrated sensor patch with screen-printing technology for in-situ and real-time monitoring of electrolyte balance and skin state. The screen-printed sensor patch was easily fabricated, highly reproducible, disposable and relatively stable, which was extremely for sweat sensors with low cost. The state of art sensors on the patch of Na+, pH, skin impedance and temperature all showed excellent performance with high linearity (coefficient of determinations (R2) are 0.998, 0.994, 0.998 and 0.997, respectively). Besides, the detection ranges of Na+ and pH sensors are wide enough for sweat analysis of 10–100 mM and 2–8, respectively. The proposed device provides a new strategy for real-time sweat analysis, preventing dehydration and skin state monitoring during exercise.

Self-reduction of bimetallic nanoparticles on flexible MXene-graphene electrodes for simultaneous detection of ascorbic acid, dopamine, and uric acid

Three-dimensional (3D) porous laser-scribed graphene (LSG) is a potential electrode material for flexible electrochemical sensors due to its high efficiency and low cost. However, the growth of nanoparticles usually depends on reducers or harsh conditions, which limit the application of flexible biosensors. To resolve this issue, 2D MXene nanosheets were applied to functionalize 3D LSG sheets with a C-O-Ti covalent crosslink and obtain an LSG-MXene hybrid scaffold. The shape-controlled Au-Pd bimetallic nanoparticles were synthesized on the surface of LSG-MXene by a self-reduction process at room temperature for 6 min to enhance its catalytic performance. As a proof of concept, the obtained hybrid nanocomposite was used to assess ascorbic acid (AA, 10–1600 μM), dopamine (DA, 12–240 μM), and uric acid (UA, 8–100, 200–800 μM). The fabricated sensor exhibited a low detection limit (S/N = 3) of 3 μM AA, 0.13 μM DA, and 1.47 μM UA. Furthermore, the Au-Pd/MXene/LSG was successfully applied to determine AA, DA, and UA in urine samples. Predictably, these outstanding performance sensors have great potential in flexible and wearable electronics.

A Mediated Enzymatic Electrochemical Sensor Using Paper-Based Laser-Induced Graphene.

Laser-induced graphene (LIG) has been applied in many different sensing devices, from mechanical sensors to biochemical sensors. In particular, LIG fabricated on paper (PaperLIG) shows great promise for preparing cheap, flexible, and disposable biosensors. Distinct from the fabrication of LIG on polyimide, a two-step process is used for the fabrication of PaperLIG. In this study, firstly, a highly conductive PaperLIG is fabricated. Further characterization of PaperLIG confirmed that it was suitable for developing biosensors. Subsequently, the PaperLIG was used to construct a biosensor by immobilizing glucose oxidase, aminoferrocene, and Nafion on the surface. The developed glucose biosensor could be operated at a low applied potential (-90 mV) for amperometric measurements. The as-prepared biosensor demonstrated a limit of detection of (50-75 µM) and a linear range from 100 µM to 3 mM. The influence of the concentration of the Nafion casting solution on the performance of the developed biosensor was also investigated. Potential interfering species in saliva did not have a noticeable effect on the detection of glucose. Based on the experimental results, the simple-to-prepare PaperLIG-based saliva glucose biosensor shows great promise for application in future diabetes management.

A powerless, gas-permeable, flexible and transparent carbon micromesh electrode for simultaneous ascorbic acid detection and pH monitoring

Ascorbic acid (AA) is a critical nutrition and chemical for humans, due to its crucial role in metabolic processes and medical treatments. It is necessary to develop a simple and rapid method for real-time tracking AA level in the body. In this work, we fabricated a powerless, gas-permeable, flexible and transparent AA biosensor based on carbon micromesh electrode (CME). The AA biosensor worked without an external power supply and exhibited excellent performances, including high transmittance (>95%), wide detection range (1 μM–1 mM), low limit of detection (10 nM), good selectivity and long-term storage stability (30 days). In addition, we integrated a pH-sensing electrode to correct the AA analysis. A layer of polyaniline (PANI) film was electrodeposited on the carbon micromesh as pH-sensing electrode that had an average sensitivity of 58.1 mV/pH with a high correlation coefficient (R2 = 0.997) within the physiological range of human body fluids (pH 4.0–8.7). To verify the availability of the CME in practical application, the Ag/C electrode was used as reference electrode to fabricate the integrated dual-functional biosensors for artificial tears detection. The CME-based biosensors showed good sensitivity, selectivity and correlation coefficient, indicating its excellent practicability towards wearable electronics.