Biosensors, Volume 12, Issue 8 (August 2022) – 117 articles

A desirable lanthanide-based ratiometric fluorescence probe was designed as a multifunctional nanoplatform for the determination of dipicolinic acid (DPA), a unique bacterial endospore biomarker, with high selectivity and sensitivity. The carbon dots (CDs) with blue emission wavelengths at 470 nm are developed with europium ion (Eu³⁺) to form Eu³⁺/CDs fluorescent probes. DPA can specifically combine with Eu³⁺ and then transfer energy from DPA to Eu³⁺ sequentially through the antenna effect, resulting in a distinct increase in the red fluorescence emission peak at 615 nm. The fluorescence intensity ratio of Eu³⁺/CDs (fluorescence intensity at 615 nm/fluorescence intensity at 470 nm) showed good linearity and low detection limit. The developed ratiometric nanoplatform possesses great potential for application in complex matrices owing to its specificity for DPA. In addition, the integration of a smartphone with the Color Picker APP installed enabled point-of-care testing (POCT) with quantitative measurement capabilities, confirming the great potential of the as-prepared measurement platform for on-site testing. Full article

Organelles are important subsystems of cells. The damage and inactivation of organelles are closely related to the occurrence of diseases. Organelles’ functional activity can be observed by fluorescence molecular tools. Nowadays, a series of aggregation-induced emission (AIE) bioprobes with organelles-targeting ability have emerged, showing great potential in visualizing the interactions between probes and different organelles. Among them, AIE luminogen (AIEgen)-based peptide bioprobes have attracted more and more attention from researchers due to their good biocompatibility and photostability and abundant diversity. In this review, we summarize the progress of AIEgen-peptide bioprobes in targeting organelles, including the cell membrane, nucleus, mitochondria, lysosomes and endoplasmic reticulum, in recent years. The structural characteristics and biological applications of these bioprobes are discussed, and the development prospect of this field is forecasted. It is hoped that this review will provide guidance for the development of AIEgen-peptide bioprobes at the organelles level and provide a reference for related biomedical research. Full article

With the rise of zoonotic diseases in recent years, there is an urgent need for improved and more accessible screening and diagnostic methods to mitigate future outbreaks. The recent COVID-19 pandemic revealed an over-reliance on RT-PCR, a slow, costly and lab-based method for diagnostics. To better manage the pandemic, a high-throughput, rapid point-of-care device is needed for early detection and isolation of patients. Electrochemical biosensors offer a promising solution, as they can be used to perform on-site tests without the need for centralized labs, producing high-throughput and accurate measurements compared to rapid test kits. In this work, we detail important considerations for the use of electrochemical biosensors for the detection of respiratory viruses. Methods of enhancing signal outputs via amplification of the analyte, biorecognition of elements and modification of the transducer are also explained. The use of portable potentiostats and microfluidics chambers that create a miniature lab are also discussed in detail as an alternative to centralized laboratory settings. The state-of-the-art usage of portable potentiostats for detection of viruses is also elaborated and categorized according to detection technique: amperometry, voltammetry and electrochemical impedance spectroscopy. In terms of integration with microfluidics, RT-LAMP is identified as the preferred method for DNA amplification virus detection. RT-LAMP methods have shorter turnaround times compared to RT-PCR and do not require thermal cycling. Current applications of RT-LAMP for virus detection are also elaborated upon. Full article

The respiratory rate is widely used for evaluating a person’s health condition. Compared to other invasive and expensive methods, the ECG-derived respiration estimation is a more comfortable and affordable method to obtain the respiration rate. However, the existing ECG-derived respiration estimation methods suffer from low accuracy or high computational complexity. In this work, a high accuracy and ultra-low power ECG-derived respiration estimation processor has been proposed. Several techniques have been proposed to improve the accuracy and reduce the computational complexity (and thus power consumption), including QRS detection using refractory period refreshing and adaptive threshold EDR estimation. Implemented and fabricated using a 55 nm processing technology, the proposed processor achieves a low EDR estimation error of 0.73 on CEBS database and 1.2 on MIT-BIH Polysomnographic Database while demonstrating a record-low power consumption (354 nW) for the respiration monitoring, outperforming the existing designs. The proposed processor can be integrated in a wearable sensor for ultra-low power and high accuracy respiration monitoring. Full article

A cost-effective, simple, flexible, and disposable colorimetric film sensor was constructed for the rapid detection of gaseous ammonia. The sensor was designed to consist of three layers, namely top, middle, and bottom layers of a polymeric elastomer. The bromocresol (BCG) indicator embedded in the middle layer of the film facilitated a change in color of the sensor from yellow-orange to blue upon exposure to gaseous ammonia. The color change was visually observed by the naked eye. The sensitivity of the sensor was verified by a successful detection of gaseous ammonia at concentrations from 4 to 235 ppm within 3 min, and the corresponding visual detection of ammonia gas was at a concentration as low as 11 ppm. The sensor also achieved a selective detection of gaseous ammonia over a variety of alkaline chemicals. The color of the sensor exposed to ammonia reverted from blue to the original yellow-orange upon subsequent exposure to the fume of acetic acid or aeration for 48 h, and it showed reliable performance for the detection of gaseous ammonia even after five repeated uses. The applicability of the sensor was validated by attaching it onto a safety helmet for a simulation of an industrial ammonia gas leak. The results indicated that our colorimetric film sensor is affordable, disposable, and reproducible, and can serve as an effective alternative for simple and rapid recognition of gaseous ammonia in environmental and air quality monitoring as well as in industrial applications. Full article

Amyloid-beta (Aβ) peptides are produced within neurons. Some peptides are released into the brain parenchyma, while others are retained inside the neurons. However, the detection of intracellular Aβ remains a challenge since antibodies against Aβ capture Aβ and its precursor proteins (i.e., APP and C99). To overcome this drawback, we recently developed 1) the C99 720-670 biosensor for recording γ-secretase activity and 2) a unique multiplexed immunostaining platform that enables the selective detection of intracellular Aβ with subcellular resolution. Using these new assays, we showed that C99 is predominantly processed by γ-secretase in late endosomes and lysosomes, and intracellular Aβ is enriched in the same subcellular loci in intact neurons. However, the detailed properties of Aβ in the acidic compartments remain unclear. Here, we report using fluorescent lifetime imaging microscopy (FLIM) that intracellular Aβ includes both long Aβ intermediates bound to γ-secretase and short peptides dissociated from the protease complex. Surprisingly, our results also suggest that the dissociated Aβ is bound to the glycoproteins on the inner membrane of lysosomes. Furthermore, we show striking cell-to-cell heterogeneity in intracellular Aβ levels in primary neurons and APP transgenic mouse brains. These findings provide a basis for the further investigation of the role(s) of intracellular Aβ and its relevance to Alzheimer’s disease (AD). Full article

Responsive two-dimensional photonic crystal (2DPC) hydrogels have been widely used as smart sensing materials for constructing various optical sensors to accurately detect different target analytes. Herein, we report photonic hydrogel aptasensors based on aptamer-functionalized 2DPC poly(acrylamide-acrylic acid-N-tert-butyl acrylamide) hydrogels for facile, label-free and colorimetric detection of lysozyme in human serum. The constructed photonic hydrogel aptasensors undergo shrinkage upon exposure to lysozyme solution through multi-factors cooperative actuation. Here, the specific binding between the aptamer and lysozyme, and the simultaneous interactions between carboxyl anions and N-tert-butyl groups with lysozyme, increase the cross-linking density of the hydrogel, leading to its shrinkage. The aptasensors’ shrinkage decreases the particle spacing of the 2DPC embedded in the hydrogel network. It can be simply monitored by measuring the Debye diffraction ring of the photonic hydrogel aptasensors using a laser pointer and a ruler without needing sophisticated apparatus. The significant shrinkage of the aptasensors can be observed by the naked eye via the hydrogel size and color change. The aptasensors show good sensitivity with a limit of detection of 1.8 nM, high selectivity and anti-interference for the detection of lysozyme. The photonic hydrogel aptasensors have been successfully used to accurately determine the concentration of lysozyme in human serum. Therefore, novel photonic hydrogel aptasensors can be constructed by designing functional monomers and aptamers that can specifically bind target analytes. Full article

Loop-mediated isothermal amplification (LAMP) is a nucleic acid amplification method that allows the simple, quick, and low-cost detection of various viral genes. LAMP assays are susceptible to generating non-specific amplicons, as high concentrations of DNA primers can give rise to primer dimerization and mismatched hybridizations, resulting in false-positive signals. Herein, we reported that poly(ethylene glycol)-engrafted nanosized graphene oxide (PEG-nGO) can significantly enhance the specificity of LAMP, owing to its ability to adsorb single-stranded DNA (ssDNA). By adsorbing surplus ssDNA primers, PEG-nGO minimizes the non-specific annealing of ssDNAs, including erroneous priming and primer dimerization, leading to the enhanced specificity of LAMP. The detection of complementary DNAs transcribed from the hepatitis C virus (HCV) RNA was performed by the PEG-nGO-based LAMP. We observed that the inclusion of PEG-nGO significantly enhances the specificity and sensitivity of the LAMP assay through the augmented difference in fluorescence signals between the target and non-target samples. The PEG-nGO-based LAMP assay greatly facilitates the detection of HCV-positive clinical samples, with superior precision to the conventional quantitative real-time PCR (RT-qPCR). Among the 20 clinical samples tested, all 10 HCV-positive samples are detected as positive in the PEG-nGO-based LAMP, while only 7 samples are detected as HCV-positive in the RT-qPCR. In addition, the PEG-nGO-based LAMP method significantly improves the detection precision for the false-positive decision by 1.75-fold as compared to the LAMP without PEG-nGO. Thus, PEG-nGO can significantly improve the performance of LAMP assays by facilitating the specific amplification of target DNA with a decrease in background signal. Full article

We have previously shown that human melanoma cells rapidly decrease human brain endothelial barrier strength. Our findings showed a fast mechanism of melanoma mediated barrier disruption, which was localised to the paracellular junctions of the brain endothelial cells. Melanoma cells are known to release molecules which cleave the surrounding matrix and allow traversal within and out of their metastatic niche. Enzymatic families, such as matrix metalloproteinases (MMPs) and proteases are heavily implicated in this process and their complex nature in vivo makes them an intriguing family to assess in melanoma metastasis. Herein, we assessed the expression of MMPs and other proteases in melanoma conditioned media. Our results showed evidence of a high expression of MMP-2, but not MMP-1, -3 or -9. Other proteases including Cathepsins D and B were also detected. Recombinant MMP-2 was added to the apical face of brain endothelial cells (hCMVECs), to measure the change in barrier integrity using biosensor technology. Surprisingly, this showed no decrease in barrier strength. The addition of potent MMP inhibitors (batimastat, marimastat, ONO4817) and other protease inhibitors (such as aprotinin, Pefabloc SC and bestatin) to the brain endothelial cells, in the presence of various melanoma lines, showed no reduction in the melanoma mediated barrier disruption. The inhibitors batimastat, Pefabloc SC, antipain and bestatin alone decreased the barrier strength. These results suggest that although some MMPs and proteases are released by melanoma cells, there is no direct evidence that they are substantially involved in the initial melanoma-mediated disruption of the brain endothelium. Full article

Cell encapsulation has been widely employed in cell therapy, characterization, and analysis, as well as many other biomedical applications. While droplet-based microfluidic technology is advantageous in cell microencapsulation because of its modularity, controllability, mild conditions, and easy operation when compared to other state-of-art methods, it faces the dilemma between high throughput and monodispersity of generated cell-laden microdroplets. In addition, the lack of a biocompatible method of de-emulsification transferring cell-laden hydrogel from cytotoxic oil phase into cell culture medium also hurtles the practical application of microfluidic technology. Here, a novel step-T-junction microchannel was employed to encapsulate cells into monodisperse microspheres at the high-throughput jetting regime. An alginate–gelatin co-polymer system was employed to enable the microfluidic-based fabrication of cell-laden microgels with mild cross-linking conditions and great biocompatibility, notably for the process of de-emulsification. The mechanical properties of alginate-gelatin hydrogel, e.g., stiffness, stress–relaxation, and viscoelasticity, are fully adjustable in offering a 3D biomechanical microenvironment that is optimal for the specific encapsulated cell type. Finally, the encapsulation of HepG2 cells into monodisperse alginate–gelatin microgels with the novel microfluidic system and the subsequent cultivation proved the maintenance of the long-term viability, proliferation, and functionalities of encapsulated cells, indicating the promising potential of the as-designed system in tissue engineering and regenerative medicine. Full article

Rapid and sensitive detection of cancer biomarkers is crucial for cancer screening, early detection, and improving patient survival rate. The present study proposes an electrochemical gene-sensor capable of detecting tumor related TP53 gene mutation hotspots by self-assembly of sulfhydryl ended hairpin DNA probes tagged with methylene blue (MB) onto a gold electrode. By performing a hybridization reaction with the target DNA sequence, the gene-sensor can rearrange the probe’s structure, resulting in significant electrochemical signal differences by differential pulse voltammetry. When the DNA biosensor is hybridized with 1 μM target DNA, the peak current response signal can decrease more than 60%, displaying high sensitivity and specificity for the TP53 gene. The biosensor achieved rapid and sensitive detection of the TP53 gene with a detection limit of 10 nmol L⁻¹, and showed good specific recognition ability for single nucleotide polymorphism (SNP) and base sequence mismatches in the TP53 gene affecting residue 248 of the P53 protein. Moreover, the biosensor demonstrated good reproducibility, repeatability, operational stability, and anti-interference ability for target DNA molecule in the complex system of 50% fetal bovine serum. The proposed biosensor provides a powerful tool for the sensitive and specific detection of TP53 gene mutation hotspot sequences and could be used in clinical samples for early diagnosis and detection of cancer. Full article

Multiple strategies have been employed to improve the performance of label-free immunosensors, among which building highly conductive interfaces and introducing suitable biocompatible carriers for immobilizing antibodies or antigens are believed to be efficient in most cases. Inspired by this, a label-free immunosensor for carcinoembryonic antigen (CEA) detection was constructed by assembling AuNPs and β-CD (Au-β-CD) on the surface of FTO modified with PANI-decorated f-MXene (MXene@PANI). Driven by the high electron conductivity of MXene@PANI and the excellent capability of Au-β-CD for antibody immobilization, the BSA/anti-CEA/Au-β-CD/MXene@PANI/FTO immunosensor exhibits balanced performance towards CEA detection, with a practical linear range of 0.5–350 ng/mL and a low detection limit of 0.0429 ng/mL. Meanwhile, the proposed sensor presents satisfying selectivity, repeatability, and stability, as well as feasibility in clinic serum samples. This work would enlighten the prospective research on the alternative strategies in constructing advanced immunosensors. Full article

The quantitative analysis of cell surface antigens has attracted increasing attention due to the antigenic variation recognition that can facilitate early diagnoses. This paper presents a novel methodology based on the optical “cell-tearing” and the especially proposed “dilution regulations” to detect variations in cell surface antigens. The cell attaches to the corresponding antibody-coated slide surface. Then, the cell-binding firmness between a single cell and the functionalized surface is assayed by optically tearing using gradually reduced laser powers incorporated with serial antibody dilutions. Groups B and B3 of red blood cells (RBCs) were selected as the experiment subject. The results indicate that a higher dilution called for lower power to tear off the cell binding. According to the proposed relative-quantitative analysis theory, antigenic variation can be intuitively estimated by comparing the maximum allowable dilution folds. The estimation result shows good consistency with the finding in the literature. This study suggests a novel methodology for examining the variation in cell surface antigens, expected to be widely capable with potential sensor applications not only in biochemistry and biophysics, but also in the micro-/nano- engineering field. Full article

Measuring continuous blood pressure (BP) in real time by using a mobile health (mHealth) application would open a new door in the advancement of the healthcare system. This study aimed to propose a real-time method and system for measuring BP without using a cuff from a digital artery. An energy-efficient real-time smartphone-application-friendly one-dimensional (1D) Squeeze U-net model is proposed to estimate systolic and diastolic BP values, using only raw photoplethysmogram (PPG) signal. The proposed real-time cuffless BP prediction method was assessed for accuracy, reliability, and potential usefulness in the hypertensive assessment of 100 individuals in two publicly available datasets: Multiparameter Intelligent Monitoring in Intensive Care (MIMIC-I) and Medical Information Mart for Intensive Care (MIMIC-III) waveform database. The proposed model was used to build an android application to measure BP at home. This proposed deep-learning model performs best in terms of systolic BP, diastolic BP, and mean arterial pressure, with a mean absolute error of 4.42, 2.25, and 2.56 mmHg and standard deviation of 4.78, 2.98, and 3.21 mmHg, respectively. The results meet the grade A performance requirements of the British Hypertension Society and satisfy the AAMI error range. The result suggests that only using a short-time PPG signal is sufficient to obtain accurate BP measurements in real time. It is a novel approach for real-time cuffless BP estimation by implementing an mHealth application and can measure BP at home and assess hypertension. Full article

There is no consensus on the role of electromyographic analysis in detecting and characterizing the asymmetries of jaw muscle excitation in patients with temporomandibular disorders (TMD). To analyze the TMD patients (n = 72) in comparison with the healthy controls (n = 30), the surface electromyography (sEMG) of the temporalis anterior muscle (TA) and masseter muscle (M) was recorded while a maximal biting task was performed. The differences in the asymmetry of the relationship between the masseter muscles were assessed in a module to determine the sensitivity (Sn) of binomial logistic models, based on the dominance of the TA or the M muscle, in accurately predicting the presence of TMD. All assumptions were met, and comparisons between the groups showed significant differences for the TA muscle ratio (p = 0.007), but not for the M muscle ratio (p = 0.13). The left side was predominant over the right side in the TMD group for both the TA (p = 0.02) and M muscles (p = 0.001), while the non-TMD group had a higher frequency of the right side. Binary logistic regression showed a significant model (χ² = 9.53; p = 0.002) for the TA muscle with Sn = 0.843. The model for the M muscle also showed significance (χ² = 8.03; p = 0.005) with Sn = 0.837. The TMD patients showed an increased TA muscle ratio and asymmetry of left dominance, compared to the healthy subjects. Both of the binomial logistic models, based on muscle dominance TA or M, were moderately sensitive for predicting the presence of TMD. Full article

This paper reports a novel micro/nanostructure co-hot embossing technique. Gold-capped nanostructures were used as localized surface plasmon resonance (SPR) sensors and were integrated into a microfluidic channel. The advantage of the co-hot embossing technique is that the SPR sensors do not need to be aligned with the microfluidic channel while bonding to it. The integrated SPR sensor and microfluidic channel were first characterized, and the sensitivity of the SPR sensor to the refractive index was found using different concentrations of glycerol solutions. The SPR sensor was also used to quantify latent membrane protein (LMP-1) when modifying anti-LMP-1 at the surface of the SPR sensor. Different concentrations of LMP-1 samples were used to build a calibration curve. Full article

Stereolithography based 3D printing of microfluidics for prototyping has gained a lot of attention due to several advantages such as fast production, cost-effectiveness, and versatility over traditional photolithography-based microfabrication techniques. However, existing consumer focused SLA 3D printers struggle to fabricate functional microfluidic devices due to several challenges associated with micron-scale 3D printing. Here, we explore the origins and mechanism of the associated failure modes followed by presenting guidelines to overcome these challenges. The prescribed method works completely with existing consumer class inexpensive SLA printers without any modifications to reliably print PDMS cast microfluidic channels with channel sizes as low as ~75 μm and embedded channels with channel sizes as low ~200 μm. We developed a custom multi-resin formulation by incorporating Polyethylene glycol diacrylate (PEGDA) and Ethylene glycol polyether acrylate (EGPEA) as the monomer units to achieve micron sized printed features with tunable mechanical and optical properties. By incorporating multiple resins with different mechanical properties, we were able to achieve spatial control over the stiffness of the cured resin enabling us to incorporate both flexible and rigid components within a single 3D printed microfluidic chip. We demonstrate the utility of this technique by 3D printing an integrated pressure-actuated pneumatic valve (with flexible cured resin) in an otherwise rigid and clear microfluidic device that can be fabricated in a one-step process from a single CAD file. We also demonstrate the utility of this technique by integrating a fully functional finger-actuated microfluidic pump. The versatility and accessibility of the demonstrated fabrication method have the potential to reduce our reliance on expensive and time-consuming photolithographic techniques for microfluidic chip fabrication and thus drastically lowering our barrier to entry in microfluidics research. Full article

Cardiovascular disease is one of the leading causes of death worldwide. Long-term and real-time monitoring of cardiovascular indicators is required to detect abnormalities and conduct early intervention in time. To this end, the development of flexible wearable/implantable sensors for real-time monitoring of various vital signs has aroused extensive interest among researchers. Among the different kinds of sensors, mechanical sensors can reflect the direct information of pressure fluctuations in the cardiovascular system with the advantages of high sensitivity and suitable flexibility. Herein, we first introduce the recent advances of four kinds of mechanical sensors for cardiovascular system monitoring, based on capacitive, piezoresistive, piezoelectric, and triboelectric principles. Then, the physio-mechanical mechanisms in the cardiovascular system and their monitoring are described, including pulse wave, blood pressure, heart rhythm, endocardial pressure, etc. Finally, we emphasize the importance of real-time physiological monitoring in the treatment of cardiovascular disease and discuss its challenges in clinical translation. Full article

A new electrochemical DNA biosensor based on mercaptopropionic acid (MPA)-capped ZnS quantum dots (MPA-ZnS QDs) immobilization matrix for covalent binding with 20-base aminated oligonucleotide has been successfully developed. Prior to the modification, screen-printed carbon paste electrode (SPE) was self-assembled with multilayer gold nanoparticles (AuNPs) and cysteamine (Cys). The inclusion of MPA-ZnS QDs semiconducting material in modified electrodes has enhanced the electron transfer between the SPE transducer and DNA leading to improved bioanalytical assay of target biomolecules. Electrochemical studies performed by cyclic voltammetry (CV) and differential pulsed voltammetry (DPV) demonstrated that the MPA-ZnS QDs modified AuNPs electrode was able to produce a lower charge transfer resistance response and hence higher electrical current response. Under optimal conditions, the immobilized synthetic DNA probe exhibited high selectivity towards synthetic target DNA. Based on the DPV response of the reduction of anthraquinone monosulphonic acid (AQMS) redox probe, the MPA-ZnS QDs-based electrochemical DNA biosensor responded to target DNA concentration from 1 × 10⁻⁹ μM to 1 × 10⁻³ μM with a sensitivity 1.2884 ± 0.12 µA, linear correlation coefficient (R²) of 0.9848 and limit of detection (LOD) of 1 × 10⁻¹¹ μM target DNA. The DNA biosensor exhibited satisfactory reproducibility with an average relative standard deviation (RSD) of 7.4%. The proposed electrochemical transducer substrate has been employed to immobilize the aminated Arowana fish (Scleropages formosus) DNA probe. The DNA biosensor showed linearity to target DNA from 1 × 10⁻¹¹ to 1 × 10⁻⁶ µM (R² = 0.9785) with sensitivity 1.1251 ± 0.243 µA and LOD of 1 × 10⁻¹¹ µM. The biosensor has been successfully used to determine the gender of Arowana fish without incorporating toxic raw materials previously employed in the hazardous processing conditions of polypyrrole chemical conducting polymer, whereby the cleaning step becomes difficult with thicker films due to high levels of toxic residues from the decrease in polymerization efficacy as films grew. Full article

Early diagnosis and treatment have always been highly desired in the fight against cancer, and detection of circulating tumor DNA (ctDNA) has recently been touted as highly promising for early cancer-screening. Consequently, the detection of ctDNA in liquid biopsy is gaining much attention in the field of tumor diagnosis and treatment, which has also attracted research interest from industry. However, it is difficult to achieve low-cost, real-time, and portable measurement of ctDNA in traditional gene-detection technology. Electrochemical biosensors have become a highly promising solution to ctDNA detection due to their unique advantages such as high sensitivity, high specificity, low cost, and good portability. Therefore, this review aims to discuss the latest developments in biosensors for minimally invasive, rapid, and real-time ctDNA detection. Various ctDNA sensors are reviewed with respect to their choices of receptor probes, designs of electrodes, detection strategies, preparation of samples, and figures of merit, sorted by type of electrode surface recognition elements. The development of biosensors for the Internet of Things, point-of-care testing, big data, and big health is analyzed, with a focus on their portable, real-time, and non-destructive characteristics. Full article

Exosomes have been gaining attention for early cancer diagnosis owing to their biological functions in cells. Several studies have reported the relevance of exosomes in various diseases, including pancreatic cancer, retroperitoneal fibrosis, obesity, neurodegenerative diseases, and atherosclerosis. Particularly, exosomes are regarded as biomarkers for cancer diagnosis and can be detected in biofluids, such as saliva, urine, peritoneal fluid, and blood. Thus, exosomes are advantageous for cancer liquid biopsies as they overcome the current limitations of cancer tissue biopsies. Several studies have reported methods for exosome isolation, and analysis for cancer diagnosis. However, further clinical trials are still required to determine accurate exosome concentration quantification methods. Recently, various biosensors have been developed to detect exosomal biomarkers, including tumor-derived exosomes, nucleic acids, and proteins. Among these, the exact quantification of tumor-derived exosomes is a serious obstacle to the clinical use of liquid biopsies. Precise detection of exosome concentration is difficult because it requires clinical sample pretreatment. To solve this problem, the use of the nanobiohybrid material-based biosensor provides improved sensitivity and selectivity. The present review will discuss recent progress in exosome biosensors consisting of nanomaterials and biomaterial hybrids for electrochemical, electrical, and optical-based biosensors. Full article

Field-effect transistors (FETs) have become eminent electronic devices for biosensing applications owing to their high sensitivity, faster response and availability of advanced fabrication techniques for their production. The device physics of this sensor is now well understood due to the emergence of several numerical modelling and simulation papers over the years. The pace of advancement along with the knowhow of theoretical concepts proved to be highly effective in detecting deadly pathogens, especially the SARS-CoV-2 spike protein of the coronavirus with the onset of the (coronavirus disease of 2019) COVID-19 pandemic. However, the advancement in the sensing system is also accompanied by various hurdles that degrade the performance. In this review, we have explored all these challenges and how these are tackled with innovative approaches, techniques and device modifications that have also raised the detection sensitivity and specificity. The functional materials of the device are also structurally modified towards improving the surface area and minimizing power dissipation for developing miniaturized microarrays applicable in ultra large scale integration (ULSI) technology. Several theoretical models and simulations have also been carried out in this domain which have given a deeper insight on the electron transport mechanism in these devices and provided the direction for optimizing performance. Full article

Precision medicine requires highly sensitive and specific diagnostic strategies with high spatiotemporal resolution. Accurate detection and monitoring of endogenously generated biomarkers at the very early disease stage is of extensive importance for precise diagnosis and treatment. Aggregation-induced emission luminogens (AIEgens) have emerged as a new type of excellent optical agents, which show great promise for numerous biomedical applications. In this review, we highlight the recent advances of AIE-based probes for detecting reactive species (including reactive oxygen species (ROS), reactive nitrogen species (RNS), reactive sulfur species (RSS), and reactive carbonyl species (RCS)) and related biomedical applications. The molecular design strategies for increasing the sensitivity, tuning the response wavelength, and realizing afterglow imaging are summarized, and theranostic applications in reactive species-related major diseases such as cancer, inflammation, and vascular diseases are reviewed. The challenges and outlooks for the reactive species-activatable AIE systems for disease diagnostics and therapeutics are also discussed. This review aims to offer guidance for designing AIE-based specifically activatable optical agents for biomedical applications, as well as providing a comprehensive understanding about the structure–property application relationships. We hope it will inspire more interesting researches about reactive species-activatable probes and advance clinical translations. Full article

Fiber Bragg grating sensors (FBGs) are considered a valid sensing solution for a variety of medical applications. The last decade witnessed the exploitation of these sensors in applications ranging from minimally invasive surgery to biomechanics and monitoring physiological parameters. Recently, preliminary studies investigated the potential impact of FBGs in the management of epidural procedures by detecting when the needle reaches the epidural space with the loss of resistance (LOR) technique. In this article, we propose a soft and flexible FBG-based system capable of detecting the LOR, we optimized the solution by considering different designs and materials, and we assessed the feasibility of the optimized soft sensor (SS) in clinical settings. The proposed SS addresses some of the open challenges in the use of a sensing solution during epidural punctures: it has high sensitivity, it is non-invasive, the sensing element does not need to be inserted within the needle, and the clinician can follow the standard clinical practice. Our analysis highlights how the material and the design impact the system response, and thus its performance in this scenario. We also demonstrated the system’s feasibility of detecting the LOR during epidural procedures. Full article

The presence of hidden allergens in food products, often due to unintended contamination along the food supply chain (production, transformation, processing, and transport), has raised the urgent need for rapid and reliable analytical methods for detecting trace levels of such species in food products. Indeed, food allergens represent a high-risk factor for allergic subjects due to potentially life-threatening adverse reactions. Portable biosensors based on immunoassays have already been developed as rapid, sensitive, selective, and low-cost analytical platforms that can replace analyses with traditional bench-top instrumentation. Recently, aptamers have attracted great interest as alternative biorecognition molecules for bioassays, since they can bind a variety of targets with high specificity and selectivity, and they enable the development of assays exploiting a variety of transduction and detection technologies. In particular, aptasensors based on luminescence detection have been proposed, taking advantage of the development of ultrasensitive tracers and enhancers. This review aims to summarize and discuss recent efforts in the field of food allergen analysis using aptamer-based bioassays with luminescence detection. Full article

The use of quartz crystal microbalance in trace mass detection is restricted by unsatisfactory sensitivity, especially in damping media, due to the worsening of the quality factor of the damping resonator. The enhancement of the sensor performance could be realized by increasing the innate resonant frequency of quartz oscillators. Herein, increased working temperature of QCM systems was proved to bring an enhancement of the original resonant frequency. In addition, the measurement of ion osmotic pressure, single layer formation and single nucleotide polymorphism (SNP) at different temperatures demonstrated that an increased working temperature could enhance the sensitivity and accuracy, suggesting a potential application in a series of trace detections. Full article

‘Metabolic burden,’ which arises when introducing exogenic synthesizing pathways into a host strain, remains a challenging issue in metabolic engineering. Redirecting metabolic flux from cell growth to product synthesis at an appropriate culture timepoint is ideal for resolving this issue. In this report, we introduce optogenetics—which is capable of precise temporal and spatial control—as a genetic switch, accompanied by the endogenous type I-E CRISPRi system in Escherichia coli (E. coli) to generate a metabolic platform that redirects metabolic flux. Poly-β-hydroxybutyric acid (PHB) production was taken as an example to demonstrate the performance of this platform. A two-to-three-fold increase in PHB content was observed under green light when compared with the production of PHB under red light, confirming the regulatory activity of this platform and its potential to redirect metabolic flux to synthesize target products. Full article

In this study, graphite rod (GR) electrodes were electrochemically modified by dendritic gold nanostructures (DGNs) followed by immobilization of glucose oxidase (GOx) in the presence of mediator phenazine methosulfate (PMS). Modified with polyaniline (PANI) or polypyrrole (Ppy), GOx/DGNs/GR electrodes were used in glucose biosensor design. Different electrochemical methods were applied for the registration of glucose concentration, and constant potential amperometry (CPA) was chosen as the best one. PANI and Ppy layers synthesized enzymatically on the GOx/DGNs/GR electrodes extended the linear glucose determination range, the width of which depended on the duration of PANI- and Ppy-layers formation. Enzymatically formed polypyrrole was determined as the most suitable polymer for the modification and formation of the glucose biosensor instead of polyaniline, because it was 1.35 times more sensitive and had a 2.57 times lower limit of detection (LOD). The developed glucose biosensor based on the Ppy/GOx/DGNs/GR electrode was characterized by appropriate sensitivity (59.4 μA mM⁻¹ cm⁻²), low LOD (0.070 mmol L⁻¹), wide linear glucose determination range (up to 19.9 mmol L⁻¹), good repeatability (8.01%), and appropriate storage stability (33 days). The performance of the developed glucose biosensor was tested in biological samples and beverages. Full article

As cyanobacterial harmful algal bloom (cHAB) events increase in scale, severity, frequency, and duration around the world, rapid and accurate monitoring and characterization tools have become critically essential for regulatory and management decision-making. The composition of cHAB-forming cyanobacteria community can change significantly over time and space and be altered by sample preservation and transportation, making in situ monitoring necessary to obtain real-time and localized information. Sandwich hybridization assay (SHA) utilizes capture oligonucleotide probes for sensitive detection of target-specific nucleic acid sequences. As an amplification-free molecular biology technology, SHA can be adapted for in-situ, real-time or near real-time detection and qualitatively or semi-quantitatively monitoring of cHAB-forming cyanobacteria, owing to its characteristics such as being rapid, portable, inexpensive, and amenable to automation, high sensitivity, specificity and robustness, and multiplexing (i.e., detecting multiple targets simultaneously). Despite its successful application in the monitoring of marine and freshwater phytoplankton, there is still room for improvement. The ability to identify a cHAB community rapidly would decrease delays in cyanotoxin analyses, reduce costs, and increase sample throughput, allowing for timely actions to improve environmental and human health and the understanding of short- and long-term bloom dynamics. Real-time detection and quantitation of HAB-forming cyanobacteria is essential for improving environmental and public health and reducing associated costs. We review and propose to apply SHA for in situ cHABs monitoring. Full article

Liquid crystals (LCs) have been widely used as sensitive elements to construct LC biosensors based on the principle that specific bonding events between biomolecules can affect the orientation of LC molecules. On the basis of the sensing interface of LC molecules, LC biosensors can be classified into three types: LC–solid interface sensing platforms, LC–aqueous interface sensing platforms, and LC–droplet interface sensing platforms. In addition, as a signal amplification method, the combination of LCs and whispering gallery mode (WGM) optical microcavities can provide higher detection sensitivity due to the extremely high quality factor and the small mode volume of the WGM optical microcavity, which enhances the interaction between the light field and biotargets. In this review, we present an overview of the basic principles, the structure, and the applications of LC biosensors. We discuss the important properties of LC and the principle of LC biosensors. The different geometries of LCs in the biosensing systems as well as their applications in the biological detection are then described. The fabrication and the application of the LC-based WGM microcavity optofluidic sensor in the biological detection are also introduced. Finally, challenges and potential research opportunities in the development of LC-based biosensors are discussed. Full article