Advances in biosensors for major depressive disorder diagnostic biomarkers.

Depression is one of the most common mental disorders and is mainly characterized by low mood or lack of interest and pleasure. It can be accompanied by varying degrees of cognitive and behavioral changes and may lead to suicide risk in severe cases. Due to the subjectivity of diagnostic methods and the complexity of patients' conditions, the diagnosis of major depressive disorder (MDD) has always been a difficult problem in psychiatry. With the discovery of more diagnostic biomarkers associated with MDD in recent years, especially emerging non-coding RNAs (ncRNAs), it is possible to quantify the condition of patients with mental illness based on biomarker levels. Point-of-care biosensors have emerged due to their advantages of convenient sampling, rapid detection, miniaturization, and portability. After summarizing the pathogenesis of MDD, representative biomarkers, including proteins, hormones, and RNAs, are discussed. Furthermore, we analyzed recent advances in biosensors for detecting various types of biomarkers of MDD, highlighting representative electrochemical sensors. Future trends in terms of new biomarkers, new sample processing methods, and new detection modalities are expected to provide a complete reference for psychiatrists and biomedical engineers.

Advances in heart failure monitoring: Biosensors targeting molecular markers in peripheral bio-fluids.

Cardiovascular diseases (CVDs), especially chronic heart failure, threaten many patients' lives worldwide. Because of its slow course and complex causes, its clinical screening, diagnosis, and prognosis are essential challenges. Clinical biomarkers and biosensor technologies can rapidly screen and diagnose. Multiple types of biomarkers are employed for screening purposes, precise diagnosis, and treatment follow-up. This article provides an up-to-date overview of the biomarkers associated with the six main heart failure etiology pathways. Plasma natriuretic peptides (BNP and NT-proBNP) and cardiac troponins (cTnT, cTnl) are still analyzed as gold-standard markers for heart failure. Other complementary biomarkers include growth differentiation factor 15 (GDF-15), circulating Galactose Lectin 3 (Gal-3), soluble interleukin (sST2), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α). For these biomarkers, the electrochemical biosensors have exhibited sufficient sensitivity, detection limit, and specificity. This review systematically summarizes the latest molecular biomarkers and sensors for heart failure, which will provide comprehensive and cutting-edge authoritative scientific information for biomedical and electronic-sensing researchers in the field of heart failure, as well as patients. In addition, our proposed future outlook may provide new research ideas for researchers.

Surface Oxygen Deficiency Enabled Spontaneous Antiprotein Fouling in WO3 Nanosheets for Biosensing in Biological Fluids.

Biofouling deteriorates the performance of sensors operated in biofluids. Protein adsorption is believed to be the first step of biofouling, which also reduces biocompatibility by further inducing cell adhesion, platelet activation, and even inflammation. Current studies of antifouling coatings are focused on polymers and hydrogels, which have succeeded in remaining resistant to protein adsorption, but their application on sensor electrodes is limited due to low conductivity and biocompatibility. Here, we report a spontaneous antibiofouling strategy for sensor electrodes by controlling oxygen vacancies in WO3 nanosheets. Irreversible adsorption of proteins was reduced by 76% in unprocessed human plasma when electrodes were coated with WO3 rich in surface oxygen vacancy. These electrodes maintained 91% of the initial current density after 1 month of incubation in human plasma.

Nanotoxicity of tungsten trioxide nanosheets containing oxygen vacancy to human umbilical vein endothelial cells.

Because of the excellent performance in photochemistry, WO3 is increasingly applied in the field of biology and medicine. However, little is known about the mechanism of WO3 cytotoxicity. In this work, WO3 nanosheets with oxygen vacancy are synthesized by solvothermal method, then characterized and added to culture medium of human umbilical vein endothelial cells (HUVECs) with different concentrations. We characterized and analyzed the morphology of nano-WO3 by transmission electron microscopy and calculated the specific data of oxygen vacancy by XPS. It is the first time the effect of WO3-x on cells that WO3-x can cause oxidative stress in HUVEC cells, resulting in DNA damage and thus promoting apoptosis. Transcriptome sequencing is performed on cells treated with low and high concentrations of WO3-x, and a series of key signals affecting cell proliferation and apoptosis are detected in differentially expressed genes, which indicates the research direction of nanotoxicity. The expression levels of key genes are also verified by quantitative PCR after cell treatment with different concentrations of WO3-x. This work fills the gap between the biocompatibility of nano WO3-x materials and molecular cytology and paves the way for investigating the mechanism and risks of oxygen vacancy in cancer therapy.

Regulating the Polypyrrole Ion-Selective Membrane and Au Solid Contact Layer to Improve the Performance of Nitrate All-Solid Ion-Selective Electrodes.

With polymerization duration and Au3+ concentration of the electrolyte regulated, a desirable nitrate-doped polypyrrole ion-selective membrane (PPy(NO3-)-ISM) and Au solid contact layer of anticipate surface morphology were obtained, and the performance of nitrate all-solid ion-selective electrodes (NS ISEs) was improved. It was found that the roughest PPy(NO3-)-ISM remarkably increases the actual contact surface area of the PPy(NO3-)-ISMs with nitrate solution, which leads to better adsorption of NO3- ions upon the PPy(NO3-)-ISMs, and produces a larger number of electrons. The most hydrophobic Au solid contact layer avoids the formation of the aqueous layer at the interface between the PPy(NO3-)-ISM and Au solid contact layer, and ensures unimpeded transporting of the produced electrons. The PPy-Au-NS ISE for polymerization duration 1800 s and at Au3+ concentration 2.5 mM of the electrolyte displays an optimal nitrate potential response, including a Nernstian slope of 54.0 mV/dec, LOD of 1.1 × 10-4 M, rapid average response time less than 1.9 s, and long-term stability of more than 5 weeks. This indicates that the PPy-Au-NS ISE is an effective working electrode for the electrochemical determination of NO3- concentration.

Evaporation issues of acoustically levitated fuel droplets.

Fuel droplet evaporation is essential to the generation of flammable mixtures in thermal engines. Generally, liquid fuel is injected directly into the hot, high-pressure atmosphere to form scattered droplets. Many investigations on droplet evaporation have been conducted with techniques involving the influence of boundaries, such as suspended wires. Ultrasonic levitation is a non-contact and non-destructive technology that can avoid the impact of hanging wire on droplet shape and heat transfer. Besides, it can simultaneously levitate multiple droplets and allow them to associate with each other or be used to study droplet instability behaviors. This paper reviews the influences of the acoustic field on levitated droplets, the evaporation characteristics of acoustically levitated droplets, and the prospects and limitations of ultrasonic suspension methods for droplet evaporation, which can serve as references for relevant studies.

Advances in Electrochemical Biosensors Based on Nanomaterials for Protein Biomarker Detection in Saliva.

The focus on precise medicine enhances the need for timely diagnosis and frequent monitoring of chronic diseases. Moreover, the recent pandemic of severe acute respiratory syndrome coronavirus 2 poses a great demand for rapid detection and surveillance of viral infections. The detection of protein biomarkers and antigens in the saliva allows rapid identification of diseases or disease changes in scenarios where and when the test response at the point of care is mandated. While traditional methods of protein testing fail to provide the desired fast results, electrochemical biosensors based on nanomaterials hold perfect characteristics for the detection of biomarkers in point-of-care settings. The recent advances in electrochemical sensors for salivary protein detection are critically reviewed in this work, with emphasis on the role of nanomaterials to boost the biosensor analytical performance and increase the reliability of the test in human saliva samples. Furthermore, this work identifies the critical factors for further modernization of the nanomaterial-based electrochemical sensors, envisaging the development and implementation of next-generation sample-in-answer-out systems.

Biomarkers and detection methods of bipolar disorder.

Bipolar disorder is one of the severe mental diseases. Its high misdiagnosis rate and long-time delayed diagnosis are related to the fact that the diagnosis procedure is mainly conducted by doctors' subjective judgment. The diagnosis methods of bipolar disorder mainly include the International Classification of Diseases (ICD) or the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria and clinical guidelines based on clinical performance. To help psychiatrists make a more accurate diagnosis, in vitro diagnostic (IVD) techniques for bipolar disorder have been developed as the biomarkers research on bipolar disorder steadily increases. Here, we systematically review the recent studies in this area, summarizing the development of instant test products, potentially benefiting clinicians and their patients. The controversy over these biomarkers is discussed, pointing out that multilevel testing with more than one biomarker may provide better confidence in diagnoses. In some cases, more attention should be paid to the different reference values of some biomarkers in terms of age, gender, etc. The review on biomarkers for bipolar disorder may open new doors for the development of point-of-care testing (POCT) and instructing the R&D of future products.

Point-of-care COPD diagnostics: biomarkers, sampling, paper-based analytical devices, and perspectives.

Chronic obstructive pulmonary disease (COPD) has become the third leading cause of global death. Insufficiency in early diagnosis and treatment of COPD, especially COPD exacerbations, leads to a tremendous economic burden and medical costs. A cost-effective and timely prevention requires decentralized point-of-care diagnostics at patients' residences at affordable prices. Advances in point-of-care (POC) diagnostics may offer new solutions to reduce medical expenditures by measuring salivary and blood biomarkers. Among them, paper-based analytical devices have been the most promising candidates due to their advantages of being affordable, biocompatible, disposable, scalable, and easy to modify. In this review, we present salivary and blood biomarkers related to COPD endotypes and exacerbations, summarize current technologies to collect human whole saliva and whole blood samples, evaluate state-of-the-art paper-based analytical devices that detect COPD biomarkers in saliva and blood, and discuss existing challenges with outlooks on future paper-based POC systems for COPD diagnosis and management.

Mitigating hook effect in one-step quantitative sandwich lateral flow assay by timed conjugate release.

Sandwich lateral flow assay (LFA) is one of the most successfully commercialized paper-based biosensors, which offers a rapid, low-cost, one-step assay. Despite its advantages, conventional sandwich LFA is fundamentally limited by the high-dose "hook" effect-a phenomenon that occurs at very high analyte concentrations and results in false-negative results. In this paper, we present a novel strategy of automatic timed detection antibody release to mitigate the hook effect in sandwich LFA without additional manual steps. We introduced an intermediate pad treated with saturated sucrose solution to regulate the flow between the nitrocellulose membrane and the conjugate pad in order to delay the reaction between detection antibodies and analytes. Using C-reactive protein (CRP) as a representative analyte, we demonstrated that our strategy exhibited a range of detection 10 times wider than that of our conventional LFA, without sacrificing the limit of detection. Comparing to other published strategies, our work could offer a one-step, cost-effective approach that is closely unified with the benefits of the LFA.

A Dynamic Threshold Cancellation Technique for a High-Power Conversion Efficiency CMOS Rectifier.

Power conversion efficiency (PCE) has been one of the key concerns for power management circuits (PMC) due to the low output power of the vibrational energy harvesters. This work reports a dynamic threshold cancellation technique for a high-power conversion efficiency CMOS rectifier. The proposed rectifier consists of two stages, one passive stage with a negative voltage converter, and another stage with an active diode controlled by a threshold cancellation circuit. The former stage conducts the signal full-wave rectification with a voltage drop of 1 mV, whereas the latter reduces the reverse leakage current, consequently enhancing the output power delivered to the ohmic load. As a result, the rectifier can achieve a voltage and power conversion efficiency of over 99% and 90%, respectively, for an input voltage of 0.45 V and for low ohmic loads. The proposed circuit is designed in a standard 130 nm CMOS process and works for an operating frequency range from 800 Hz to 51.2 kHz, which is promising for practical applications.

Photodynamic Therapy Review: Principles, Photosensitizers, Applications, and Future Directions.

Photodynamic therapy (PDT) is a minimally invasive therapeutic modality that has gained great attention in the past years as a new therapy for cancer treatment. PDT uses photosensitizers that, after being excited by light at a specific wavelength, react with the molecular oxygen to create reactive oxygen species in the target tissue, resulting in cell death. Compared to conventional therapeutic modalities, PDT presents greater selectivity against tumor cells, due to the use of photosensitizers that are preferably localized in tumor lesions, and the precise light irradiation of these lesions. This paper presents a review of the principles, mechanisms, photosensitizers, and current applications of PDT. Moreover, the future path on the research of new photosensitizers with enhanced tumor selectivity, featuring the improvement of PDT effectiveness, has also been addressed. Finally, new applications of PDT have been covered.

Regulation of the Volume Flow Rate of Aqueous Methyl Blue Solution and the Wettability of CuO/ZnO Nanorods to Improve the Photodegradation Performance of Related Microfluidic Reactors.

Six CuO/ZnO nanorod (CuO/ZnONR)-based microfluidic reactors were constructed for different UV irradiation durations, with which an aqueous methylene blue (MB) solution was photodegraded at varied volume flow rate Q. Via numerical and experimental routes, the effects of the Q on the kinetic adsorption rate constant Ka and the initial rate constant KA of the CuO/ZnONR-based microfluidic reactors were discussed. Moreover, a reverse contacting angle (CA) trend of CuO/ZnONRs to the reaction constant K curve of corresponding CuO/ZnONR-based microfluidic reactor suggested that the CA of CuO/ZnONRs was another key influencing factor that affected greatly the photodegradation performance of the microfluidic reactors. The Q of the aqueous MB solution and the UV irradiation duration for the photodeposition of CuO/ZnONRs were optimized to be 125 µL/min and 1.0 h, the K of the CuO/ZnONR-based microfluidic reactors reached 4.84 min-1, and the related ΔKA/K was less than 6%. Similarly, these methods and results can be employed not only to enhance the mass transport and adsorption of specific species within other nanostructured matrix material-coated microchannels but also to enlarge the actual contacting surface areas between these microchannels and the related solution, which further improve the performance of other nanostructured catalyst-based microfluidic reactors, rGO microfluidic voltage generation, and a GOx/AuNW enzymatic glucose microfluidic sensor.

An ultrasensitive fluorimetric sensor for pre-screening of water microbial contamination risk.

In recent years, global efforts have been directed towards the development of water safety routines, consequently demanding cost-effective sensors capable of detecting outbreaks at early stages. This work reports the development and study of an original in-field tryptophan fluorimetric sensor as a potential indicator of real-time microbial contamination in water. The sensor excitation and emission wavelengths were selected with respect to the coliform bacteria tryptophan peak; 280 nm for excitation and 330 nm for emission. The in-lab tests with standard samples show a detection limit of 4.89 nM (≈0.1 µg/l) for L-tryptophan. The sensor exhibited good linearity over three orders of magnitude and considerable detection reproducibility, which was confirmed during calibration tests. Small-scale in situ tests showed that the sensor was better correlated with coliform bacteria than other online sensors such as turbidity. This suggests that the fluorimetric tryptophan sensor can be integrated into early warning systems that quickly assess changes in water microbial quality.

Recent methods and biosensors for foodborne pathogen detection in fish: progress and future prospects to sustainable aquaculture systems.

The aquaculture industry has advanced toward sustainable recirculating systems, in where parameters of food quality are strictly monitored. Despite that, as in the case of conventional aquaculture practices, the recirculating systems also suffer threats from Aeromonas spp., Vibrio spp., Streptococcus spp., among other foodborne pathogens infecting farmed fish. The aquaculture pathogens are routinely detected by conventional PCR methods or antibody-based tests, with the detection protocols confined to laboratory use. Emerging assay technologies and biosensors recently reported in the literature open new opportunities to the development of sensitive, specific, and portable analytical devices to use in the field. Techniques of DNA/RNA analysis, immunoassays and other nanomolecular technologies have been facing important advances in response time, sensitivity, and enhanced power of discrimination among and within species. Moreover, the recent developments of electrochemical and optical signal transduction have facilitated the incorporation of the innovative assays to practical miniaturized devices. In this work, it is provided a critical review over foodborne pathogen detection by existing and promising methods and biosensors applied to fish samples and extended to other food matrices. While isothermal DNA/RNA amplification methods can be highlighted among the assay methods for their promising analytical performance and suitability for point-of-care testing, the electrochemical transduction provides a way to achieve cost-effective biosensors amenable to use in the aquaculture field. The adoption of new methods and biosensors would constitute a step forward in securing sustainable aquaculture systems.

Sputum and salivary protein biomarkers and point-of-care biosensors for the management of COPD.

Chronic obstructive pulmonary disease (COPD) has become one of the most fatal diseases of the century considering mortality and morbidity levels worldwide. This disease is an inflammatory response to environmental stress and tobacco smoking. Although spirometry is the gold-standard diagnostic test administrated in primary and secondary care, it often exhibits low accuracy in cases of predicting disease worsening and possible bias due to the operator, patient, and conditions. Recent developments in proteomics research suggest that the presence of protein biomarkers can aid in the accurate diagnosis and prediction of disease outcomes. This review presents the cutting-edge research progress in the area of protein biomarkers towards the management of COPD. The literature review was confined to protein biomarkers in saliva and sputum because testing these bodily fluids shows great promise for point-of-care (POC) testing due to its practicality, non-invasiveness and inexpensive handling and sampling. Although it is conclusive that more studies on sputum and saliva are needed, this review studies the promising clinical value of interleukin (IL)-6 and IL-8, matrix metalloproteinase (MMP)-8 and MMP-9, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and neutrophil elastase (NE). Following the critical analysis of salivary and sputum biomarkers, the recent development of POC biosensors for the multiplexed detection of biomarkers is also reported. Overall, the review aims to explore the possibility for the future development of POC sensors for chronic lung disease management utilizing clinically relevant biomarkers in saliva and sputum.

A Fluorescence Sensing Method with Reduced DNA Typing and Low-Cost Instrumentation for Detection of Sample Tampering Cases in Urinalysis.

This work presents a method to unequivocally detect urine sample tampering in cases where integrity of the sample needs to be verified prior to urinalysis. The technique involves the detection of distinct patterns of a triplex short tandem repeats system in DNA extracted from human urine. The analysis is realized with single-dye fluorescence detection and using a regular smartphone camera. The experimental results had demonstrated the efficacy of the analytical approach to obtaining distinct profiles of amplicons in urine from different sample providers. Reproducibility tests with fresh and stored urine have revealed a maximum variation in the profiles within an interval of 5 to 9%. Cases of urine sample tampering via mixture were simulated in the study, and the experiments have identified patterns of mixed genotypes from dual mixtures of urine samples. Moreover, sample adulteration by mixing a non-human fluid with urine in a volume ratio over 25% can be detected. The low cost of the approach is accompanied by the compatibility of the technique to use with different DNA sample preparation protocols and PCR instrumentation. Furthermore, the possibility of realizing the method in an integrated microchip system open great perspectives to conducting sample integrity tests at the site of urine sample reception and/or at resource-limited settings.

Electrochemical methods for detection of biomarkers of Chronic Obstructive Pulmonary Disease in serum and saliva.

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death nowadays, and its underdiagnosis is still a great challenge. More effective diagnosis method is in urgent need since the traditional spirometry has many limitations in the practical application. The electrochemical (EC) detection methods have their unique advantages of high accuracy, short response time and easy integration of the system. In this review, recent works on the EC methods for COPD biomarkers including interleukin 6 (IL-6), interleukin 8 (IL-8) and C-reactive protein (CRP) are summarized. Five types of EC methods are highlighted in this study, as enzyme-labelled immunosensors, nanoparticle-labelled immunosensors, capacitive or impedimetric immunosensors, magnetoimmunosensors, and field effect transistor (FET) immunosensors. To date, EC immunosensors have been exhibiting high analytical performance with a detection limit that can achieve several pg/mL or even lower. The simplicity of EC immunosensors makes them a perfect solution for a future point-of-care device to use in settings for COPD diagnosis and follow-up. Nevertheless, more efforts need to be paid on the simultaneous detection of multiple biomarkers, a demand for the clinical diagnosis, and processes of assay simplification towards achieving one-step detection.

A fluorimetric nitrite biosensor with polythienothiophene-fullerene thin film detectors for on-site water monitoring.

A novel fluorimetric sensor for highly sensitive nitrite detection on the site is presented in this study. The proposed on-chip approach comprises the use of integrated polymer photodetectors to detect light from fluorescence reactions with a diaminofluorescein probe. The detectors were prepared with a heterostructured nanofilm of polythieno[3,4-b]thiophene/benzodithiophene and (6,6)-phenyl-C71-butyric-acid methyl-ester as a photoactive layer. Prior to fluorimetric detection, the quality of the spin-coated photoactive layer was characterized via nano-morphology and current-density measurements. Nitrite assays were conducted on a poly(methyl methacrylate) microchannel chip, to which polythienothiophene-C71 based detectors were aligned. Results of signal-to-noise ratio determination have indicated a detection limit below 0.55 µM, lower than the 0.1 mg L-1 maximum limit of operation in recirculating aquaculture systems for farming Atlantic salmon Salmo salar. An increase of the nitrite concentration to toxic levels may therefore be possible to detect. The fluorimetric sensor exhibited good linearity over three orders of magnitude and acceptable detection reproducibility, which confirmed its analytical value. Further tests revealed great promise of the integrated biosensor device for detecting nitrite in aquaculture-relevant samples with high precision. The approach reported hereby may provide impetus to in situ analytical tools for monitoring water quality at aquaculture facilities, the food industries or water monitoring stations.

PDMS Microlenses for Focusing Light in Narrow Band Imaging Diagnostics.

Minimally invasive medical devices can greatly benefit from Narrow Band Imaging (NBI) diagnostic capabilities, as different wavelengths allow penetration of distinct layers of the gastrointestinal tract mucosa, improving diagnostic accuracy and targeting different pathologies. An important performance parameter is the light intensity at a given power consumption of the medical device. A method to increase the illumination intensity in the NBI diagnostic technique was developed and applied to minimally invasive medical devices (e.g., endoscopic capsules), without increasing the size and power consumption of such instruments. Endoscopic capsules are generally equipped with light-emitting diodes (LEDs) operating in the RGB (red, green, and blue) visible light spectrum. A polydimethylsiloxane (PDMS) µ-lens was designed for a maximum light intensity at the target area of interest when placed on top of the LEDs. The PDMS µ-lens was fabricated using a low-cost hanging droplet method. Experiments reveal an increased illumination intensity by a factor of 1.21 for both the blue and green LEDs and 1.18 for the red LED. These promising results can increase the resolution of NBI in endoscopic capsules, which can contribute to early gastric lesions diagnosis.