Immunotherapy Study on Non-small-Cell Lung Cancer (NSCLC) Combined with Cytotoxic T Cells and miRNA34a.

Immunotherapy has emerged as a promising approach for cancer treatment, and the use of microRNAs (miRNAs) as therapeutic agents has gained significant attention. In this study, we investigated the effectiveness of immunotherapy utilizing miRNA34a and Jurkat T cells in inducing cell death in non-small-cell lung cancer cells, specifically A549 cells. Moreover, we explored the impact of Jurkat T cell activation and miRNA34a delivery using iron oxide nanorods (IONRs) on the killing of cancer cells. A549 cells were cocultured with both activated and inactivated Jurkat T cells, both before and after the delivery of miRNA34a. Surprisingly, our results revealed that even inactive Jurkat T cells were capable of inducing cell death in cancer cells. This unexpected observation suggested the presence of alternative mechanisms by which Jurkat T cells can exert cytotoxic effects on cancer cells. We stimulated Jurkat T cells using anti-CD3/CD28 and analyzed their efficacy in killing A549 compared to that of the inactive Jurkat T cells in conjunction with miRNA34a. Our findings indicated that the activation of Jurkat T cells significantly enhanced their cytotoxic potential against cancer cells compared to their inactive counterparts. The combined treatment of A549 cells with activated Jurkat T cells and miRNA34a demonstrated the highest level of cancer cell death, suggesting a synergistic effect between Jurkat T cell activation and miRNA therapy. Besides the apoptosis mechanism for the Jurkat T cells' cytotoxic effects on A549 cells, we furthermore investigated the ferroptosis pathway, which was found to have an impact on the cancer cell killing due to the presence of miRNA34a and IONRs as the delivery agent inside the cancer cells.

Redox-Concatenated Aptamer Integrated Skin Mimicking Electrochemical Patch for Noninvasive Detection of Cortisol.

This research focuses on developing and validating a wearable electrochemical biosensor called the concatenated aptamer integrated skin patch, also known as the Captain Patch. The main objective is to detect cortisol levels in sweat, which can provide valuable insights into an individual's health. The biosensor utilizes a corrugated surface that mimics the skin, allowing for better attachment and an improved electrochemical performance. The study demonstrates the successful application of Captain Patch on the human body by using artificially spiked sweat samples. The results indicate good measurement accuracy and conformity when the patch is worn on the body. However, for long-term usage, the patch needs to be changed every 3-4 h or worn three times a day to enable monitoring of cortisol levels. Despite the need for frequent patch changes, the cost-effectiveness and ease of operation make these skin patches suitable for longitudinal cortisol monitoring and other sweat analytes. By customization of the biorecognition probe, the developed biowearable can be used to monitor a variety of vital biomarkers. Overall, Captain Patch, with its capability of detecting specific health markers such as cortisol, hints at the future potential of wearables to offer valuable data on various other biomarkers. Our approach presents the first step in integrating a cost-effective wearable electrochemical patch integrated with a redox-concatenated aptamer for noninvasive biomarker detection. This personalized approach to monitoring can lead to improved patient outcomes and increased patient engagement in managing their health.

A study report on the effect of COVID-19 pandemic in providing in-and-out-patient psychiatric services in a level-3 COVID hospital.

Background: COVID-19 pandemic disrupted all routine and emergency hospital services, including our out-and-in-patient psychiatric services. Aim: To study the effect of the COVID-19 pandemic and subsequent lockdown in providing in-and-out-patient psychiatric services and the experience of tele-consultation services in our level-3 COVID hospital. Materials and Methods: We conducted a retrospective observational study using an administrative database at psychiatry in-and-out-patient department. All the cases that were reported to us, through emergency Out-Patient Department (OPD) and tele-consultation OPD, from April 2020 to October 2020, were included in the study. Data, thus obtained, were compared with the out-and-in-patient data during the same period on the previous year. Results: During the study period, there was a decline in out-patient registration of patients by 94.5%, and a reduction in admission rate was 75.5%, in comparison with the previous year. During 3 months of tele-consultation service provided, 23.5% of patients had the diagnosis of depression, 21.4% of them had various types of headaches, 15.9% of patients had psychosis, 15.3% had anxiety disorders, and 8.8% had a bipolar-affective disorder. Conclusion: Being a level-3 COVID hospital, our hospital suffered significantly in relation to psychiatric in-and-out-patients attendance and service recipients during the study period of COVID-19 pandemic.

Characterization and antimicrobial evaluation of anthraquinones and triterpenes from Rubia cordifolia.

Chemical investigation of roots of the plant, Rubia cordifolia Linn, led to the isolation of an undescribed anthraquinone, cordifoquinone R, determined as 1,2-dihydroxy-6-methoxyanthracene-9,10-dione (6) based on the 1D and 2D NMR analyses and HRESIMS. Ten other known compounds viz.1,4-dihydroxy-2-methoxyanthracene-9,10-dione (1), rubiadin (2), xanthopurpurin (3), 1-methoxy-3-hydroxy-2-carbomethoxy-9,10-anthraquinone (4), alizarin (5), ß-sitosterol glucoside (7), scopoletin (8), oleanolic acid, (9), pomolic acid (10), queretaroic acid (11) were also isolated. Out of these compounds, 4, 10, and 11 are first reported from this plant species. Compounds 2, 3, 6, 7, and 10 showed activity in the range of 16-32 µg/ml against S. aureus ATCC 29213.

Comparing the Variants of Iron Oxide Nanoparticle-Mediated Delivery of miRNA34a for Efficiency in Silencing of PD-L1 Genes in Cancer Cells.

The blocking of programmed death-ligand 1 (PD-L1) in tumor cells represents a powerful strategy in cancer immunotherapy. Using viral vectors to deliver the cargo for inactivating the PD-L1 gene could be associated with host cell genotoxicity and concomitant immune attack. To develop an alternative safe gene delivery method, we designed a unique combination for miRNA34a delivery using a transgene carrier in the form of iron oxide magnetic nanoparticles (IONPs) via magnetofection to downregulate PD-L1 expression in cancer cells. We synthesized IONPs of multiple shapes (IONRs (iron oxide nanorods), IONSs (iron oxide nanospheres), and ITOHs (iron oxide truncated octahedrons)), surface-functionalized with polyethyleneimine (PEI) using the ligand exchange method, as gene delivery systems. Under the guidance of an external magnetic field, PEI@IONPs loaded with plasmid DNA (DNA/PEI@IONPs) encoding GFP showed high transfection efficiency at different weight ratios and time points in A549 and MDA-MB-231 cells. Additionally, the DNA/PEI@IONPs with miRNA34a inserts under a static magnetic field resulted in significant knockdown of the PD-L1 gene, as demonstrated via immunoblotting of the PD-L1 protein. Among the three shapes of IONPs, IONRs showed the highest PD-L1 knockdown efficiency. The genetic expression of miRNA34a was also studied using qPCR and it showed high expression of miRNA in cells treated with PEI@IONRs. Flow cytometry and a live/dead assay confirmed apoptosis after transfection with miRNA34a. To conclude, in this paper, a promising transgene carrier with low cost, negligible cytotoxicity, and high transfection efficiency has been successfully established for miRNA gene delivery in the context of cancer immunotherapy.

Electrochemical DNAzyme-based biosensors for disease diagnosis.

DNAzyme-based electrochemical biosensors provide exceptional analytical sensitivity and high target recognition specificity for disease diagnosis. This review provides a critical perspective on the fundamental and applied impact of incorporating DNAzymes in the field of electrochemical biosensing. Specifically, we highlight recent advances in creating DNAzyme-based electrochemical biosensors for diagnosing infectious diseases, cancer and regulatory diseases. We also develop an understanding of challenges around translating the research in the field of DNAzyme-based electrochemical biosensors from labs to clinics, followed by a discussion on different strategies that can be applied to enhance the performance of the currently existing technologies to create truly point-of-care electrochemical DNAzyme biosensors.

Altered sperm fate in the reproductive tract milieu due to oxidative stress leads to sub-fertility in type 1 diabetes females: A Drosophila-based study.

AIMS: Female sub-fertility, a prominent complication due to Type 1 diabetes (T1D), is generally attributed to disturbances in menstrual cycles and/or ovarian defects/disorders. T1D women, however, are high in oxidative stress, although the impact of the same on their reproduction and associated events remains unknown. Therefore, we assessed the repercussions of elevated oxidative stress on the sperm fate (storage/utilization) in the reproductive tract milieu of T1D females and their fertility using the Drosophila T1D model (Df[dilp1-5]), which lacks insulin-like peptides and displays reduced female fertility. MAIN METHODS: We mated Df[dilp1-5] females to normal males and thereafter examined sperm storage and/or utilization in conjunction with oxidative stress parameters in mated Df[dilp1-5] females at different time points. Also, the impact of antioxidant (Amla or Vitamin C) supplementation on the above oxidative stress parameters in Df[dilp1-5] females and the consequences on their sperm and fertility levels were examined. KEY FINDINGS: Df[dilp1-5] females showed elevated oxidative stress parameters and a few of their reproductive tract proteins are oxidatively modified. Also, these females stored significantly fewer sperm and also did not utilize sperm as efficiently as their controls. Surprisingly, amelioration of the oxidative stress in Df[dilp1-5] females' milieu through antioxidant (Amla or vitamin C) supplementation enhanced sperm storage and improved fertility. SIGNIFICANCE: Hyperglycemia coupled with elevated oxidative stress within the female reproductive tract environment affects the sperm fate, thereby reducing female fertility in T1D. In addition, these findings suggest that antioxidant supplementation may substantially aid in the mitigation of sub-fertility in T1D females.

Recent Advances, Opportunities, and Challenges in Developing Nucleic Acid Integrated Wearable Biosensors for Expanding the Capabilities of Wearable Technologies in Health Monitoring.

Wearable biosensors are becoming increasingly popular due to the rise in demand for non-invasive, real-time monitoring of health and personalized medicine. Traditionally, wearable biosensors have explored protein-based enzymatic and affinity-based detection strategies. However, in the past decade, with the success of nucleic acid-based point-of-care diagnostics, a paradigm shift has been observed in integrating nucleic acid-based assays into wearable sensors, offering better stability, enhanced analytical performance, and better clinical applicability. This narrative review builds upon the current state and advances in utilizing nucleic acid-based assays, including oligonucleotides, nucleic acid, aptamers, and CRISPR-Cas, in wearable biosensing. The review also discusses the three fundamental blocks, i.e., fabrication requirements, biomolecule integration, and transduction mechanism, for creating nucleic acid integrated wearable biosensors.

A DNA Barcode-Based Aptasensor Enables Rapid Testing of Porcine Epidemic Diarrhea Viruses in Swine Saliva Using Electrochemical Readout.

Pen-side testing of farm animals for infectious diseases is critical for preventing transmission in herds and providing timely intervention. However, most existing pathogen tests have to be conducted in centralized labs with sample-to-result times of 2-4 days. Herein we introduce a test that uses a dual-electrode electrochemical chip (DEE-Chip) and a barcode-releasing electroactive aptamer for rapid on-farm detection of porcine epidemic diarrhea viruses (PEDv). The sensor exploits inter-electrode spacing reduction and active field mediated transport to accelerate barcode movement from electroactive aptamers to the detection electrode, thus expediting assay operation. The test yielded a clinically relevant limit-of-detection of 6 nM (0.37 µg mL-1 ) in saliva-spiked PEDv samples. Clinical evaluation of this biosensor with 12 porcine saliva samples demonstrated a diagnostic sensitivity of 83 % and specificity of 100 % with a concordance value of 92 % at an analysis time of one hour.

DNAzyme-Immobilizing Microgel Magnetic Beads Enable Rapid, Specific, Culture-Free, and Wash-Free Electrochemical Quantification of Bacteria in Untreated Urine.

Rapid, ultrasensitive, and specific detection and identification of bacteria in unprocessed clinical specimens is critically needed to enable point-of-care diagnosis of infectious diseases. However, existing systems require sample processing and/or analyte enrichment for direct bacterial analysis in clinical samples, which significantly adds to the assay time and complexity. Herein, we integrate RNA-cleaving DNAzymes specific to Escherichia coli (E. coli) and programmed for electrochemical signal transduction, multifunctional microgel magnetic beads for immobilizing the DNAzyme into a hydrated and three-dimensional scaffold, and hierarchical electrodes for ultrasensitive electrochemical readout to achieve rapid bacterial analysis in undiluted and unprocessed urine collected from symptomatic patients suspected of having urinary tract infections (UTIs). The microgel magnetic bead assay enables highly efficient conjugation and hydration of the immobilized DNAzymes, resulting in low limits-of-detection of 6 CFU/mL in buffer and 138 CFU/mL in unprocessed urine with high specificity against multiple urinary pathogens within a 1 hour assay time. The assay successfully identifies which patients are infected with E. coli as the causative organism for their UTI symptoms, indicating the clinical relevance of this assay.

Ethanolic Extract of Tridax procumbens Mitigates Pulmonary Inflammation via Inhibition of NF-κB/p65/ERK Mediated Signalling in an Allergic Asthma Model.

BACKGROUND: Tridax procumbens is a traditionally used medicinal plant with high content of active phytoconstituents having anti-inflammatory activity. Accumulating evidences have shown that Tridax procumbens efficaciously diminished oxidative stress and inflammation. However the anti-inflammatory role of Tridax procumbens is not obscured in allergic asthma. PURPOSE: Aim of this study was to decipher the anti-inflammatory role of Tridax procumbens in allergic asthma and its underlying mechanism. METHODS: Ethanolic extract of Tridax procumbens (TP) was prepared and major phytoconstituents (flavonoids) were characterized by biochemical and UPLC/MS analysis. Rats were sensitized and challenged with environmental allergen ovalbumin (OVA) and lipopolysaccharide (LPS) to establish an allergic asthma model. Persuasive anti-inflammatory role of TP was demonstrated in vivo (100, 200 and 400 mg/kg) and in vitro (250, 125, 75 and 25 µg/ml) experiments. RESULTS: Characterization by UPLC/MS analysis showed the presence of various bioactive flavonoids. In in vitro study, significant reduction in ROS production, apoptosis and mitochondrial dysfunction were observed in alveolar type II cells upon pre-treatment with TP (250, 125, 75 and 25 µg/ml) in a concentration-dependant manner. In vivo, TP (200 mg/kg) oral administration showed robust anti-oxidative activity. TP treatment abrogated bronchial wall thickening, immune cell infiltration and bronchial wall fibre deposition. Immunohistochemical analysis showed the diminished expression of IL-1ß, IL-6 in bronchial epithelium and vascular endothelium. TP abrogated inflammation by reducing the level of inflammatory cytokines including IL-2, IFN-γ, IL-6 and MCP-1, as well as inflammatory markers including TWEAK, TNF-α, TNF-R1 and its downstream transcription factor NF-Ò¡B/p65 activation and its nuclear translocation. Western blot analysis of TP treated lung tissue and alveolar type II cells showed reduced phosphorylation of ERK1/2 significantly. CONCLUSION: TP exhibited anti-inflammatory activity by inhibition of ROS production and down-regulation of NF-Ò¡B/ERK signalling in vitro and in vivo asthma model. Thus, TP can be envisaged as an effective anti-inflammatory agent for OVA-induced allergic asthma.

Two-Step Competitive Hybridization Assay: A Method for Analyzing Cancer-Related microRNA Embedded in Extracellular Vesicles.

With an increased understanding of the role of microRNAs (miRNAs) in cancer evolution, there is a growing interest in the use of these non-coding nucleic acids in cancer diagnosis, prognosis, and treatment monitoring. miRNAs embedded in extracellular vesicles (EVs) are of particular interest given that circulating EVs carry cargo that are strongly correlated to their cells of origin such as tumor cells while protecting them from degradation. As such, there is a tremendous interest in new simple-to-operate vesicular microRNA analysis tools for widespread use in performing liquid biopsies. Herein, we present a two-step competitive hybridization assay that is rationally designed to translate low microRNA concentrations to large electrochemical signals as the measured signal is inversely proportional to the microRNA concentration. Using this assay, with a limit-of-detection of 122 aM, we successfully analyzed vesicular miRNA 200b from prostate cancer cell lines and human urine samples, demonstrating the expected lower expression levels of miRNA 200b in the EVs from prostate cancer cells and in the prostate cancer patient's urine samples compared to healthy patients and non-tumorigenic cell lines, validating the suitability of our approach for clinical analysis.

High-Affinity Dimeric Aptamers Enable the Rapid Electrochemical Detection of Wild-Type and B.1.1.7 SARS-CoV-2 in Unprocessed Saliva.

We report a simple and rapid saliva-based SARS-CoV-2 antigen test that utilizes a newly developed dimeric DNA aptamer, denoted as DSA1N5, that specifically recognizes the spike proteins of the wildtype virus and its Alpha and Delta variants with dissociation constants of 120, 290 and 480 pM, respectively, and binds pseudotyped lentiviruses expressing the wildtype and alpha trimeric spike proteins with affinity constants of 2.1 pM and 2.3 pM, respectively. To develop a highly sensitive test, DSA1N5 was immobilized onto gold electrodes to produce an electrochemical impedance sensor, which was capable of detecting 1000 viral particles per mL in 1:1 diluted saliva in under 10 min without any further sample processing. Evaluation of 36 positive and 37 negative patient saliva samples produced a clinical sensitivity of 80.5 % and specificity of 100 % and the sensor could detect the wildtype virus as well as the Alpha and Delta variants in the patient samples, which is the first reported rapid test that can detect any emerging variant of SARS-CoV-2.

Integrating programmable DNAzymes with electrical readout for rapid and culture-free bacterial detection using a handheld platform.

The detection and identification of bacteria currently rely on enrichment steps such as bacterial culture and nucleic acid amplification to increase the concentration of target analytes. These steps increase assay time, cost and complexity, making it difficult to realize a truly rapid point-of-care test. Here we report the development of an electrical assay that uses electroactive RNA-cleaving DNAzymes (e-RCDs) to identify specific bacterial targets and subsequently release a DNA barcode for transducing a signal onto an electrical chip. Integrating e-RCDs into a two-channel electrical chip with nanostructured electrodes provides the analytical sensitivity and specificity needed for clinical analysis. The e-RCD assay is capable of detecting 10 CFU (equivalent to 1,000 CFU ml-1) of Escherichia coli selectively from a panel containing multiple non-specific bacterial species. Clinical evaluation of this assay using 41 patient urine samples demonstrated a diagnostic sensitivity of 100% and specificity of 78% at an analysis time of less than one hour compared with the several hours needed for currently used culture-based methods.

Enhancing the Sensitivity of Photoelectrochemical DNA Biosensing Using Plasmonic DNA Barcodes and Differential Signal Readout.

Photoelectrochemical biosensors hold great promise for sensitive bioanalysis; however, similar to their electrochemical analogues, they are highly affected by the variable backgrounds caused by biological matrices. We developed a new PEC biosensing strategy that uses differential signal generation, combining signals from two separate but correlated binding events on the biosensor, for improving the limit-of-detection, sensitivity, and specificity of PEC DNA biosensors in biological samples. In this assay, the binding of unlabeled target DNA is followed by the capture of a signal amplification barcode featuring a plasmonic nanoparticle. The interaction of the plasmonic barcode with the semiconductive building blocks of the biosensor results in significant signal amplification, and together with differential signal processing enhances the limit of detection and sensitivity of the assay by up to 15- and three-fold, respectively, compared to the previously-used PEC assays with a single binding event, demonstrating a limit of detection of 3 fM.

Dynamic Bio-Barcode Assay Enables Electrochemical Detection of a Cancer Biomarker in Undiluted Human Plasma: A Sample-In-Answer-Out Approach.

There is a need for biosensing systems that can be operated at the point-of-care (POC) for disease screening and diagnostics and health monitoring. In spite of this, simple to operate systems with the required analytical sensitivity and specificity in clinical samples, using a sample-in-answer-out approach, remain elusive. Reported here is an electrochemical bio-barcode assay (e-biobarcode assay) that integrates biorecognition with signal transduction using molecular (DNA/protein) machines and signal readout using nanostructured electrodes. The e-biobarcode assay eliminates multistep processing and uses a single step for analysis following sample collection into the reagent tube. A clinically relevant performance for the analysis of prostate specific antigen (PSA) in undiluted and unprocessed human plasma: a log-linear range of 1 ng mL-1 -200 ng mL-1 and a LOD of 0.4 ng mL-1 , was achieved. The e-biobarcode assay offers a realistic solution for biomarker analysis at the POC.

Roadmap to the Bioanalytical Testing of COVID-19: From Sample Collection to Disease Surveillance.

The disease caused by SARS-CoV-2, coronavirus disease 2019 (COVID-19), has led to a global pandemic with tremendous mortality, morbidity, and economic loss. The current lack of effective vaccines and treatments places tremendous value on widespread screening, early detection, and contact tracing of COVID-19 for controlling its spread and minimizing the resultant health and societal impact. Bioanalytical diagnostic technologies have played a critical role in the mitigation of the COVID-19 pandemic and will continue to be foundational in the prevention of the subsequent waves of this pandemic along with future infectious disease outbreaks. In this Review, we aim at presenting a roadmap to the bioanalytical testing of COVID-19, with a focus on the performance metrics as well as the limitations of various techniques. The state-of-the-art technologies, mostly limited to centralized laboratories, set the clinical metrics against which the emerging technologies are measured. Technologies for point-of-care and do-it-yourself testing are rapidly emerging, which open the route for testing in the community, at home, and at points-of-entry to widely screen and monitor individuals for enabling normal life despite of an infectious disease pandemic. The combination of different classes of diagnostic technologies (centralized and point-of-care and relying on multiple biomarkers) are needed for effective diagnosis, treatment selection, prognosis, patient monitoring, and epidemiological surveillance in the event of major pandemics such as COVID-19.

Differential Photoelectrochemical Biosensing Using DNA Nanospacers to Modulate Electron Transfer between Metal and Semiconductor Nanoparticles.

As dynamic biorecognition agents such as functional nucleic acids become widely used in biosensing, there is a need for ultrasensitive signal transduction strategies, beyond fluorescence, that are robust and stable for operation in heterogeneous biological samples. Photoelectrochemical readout offers a pathway toward this goal as it offers the simplicity and scalability of electrochemical readout, in addition to compatibility with a broad range of nanomaterials used as labels for signal transduction. Here, a differential photoelectrochemical biosensing approach is reported, in which DNA nanospacers are used to program the response of two sensing channels. The differences in the motional dynamics of DNA probes immobilized on different channels are used to control the interaction between Au and TiO2 nanoparticles positioned at the two ends of the DNA nanospacer to achieve differential signal generation. Depending on the composition of the DNA constructs (fraction of the DNA sequence i.e., double-stranded), the channels can be programmed to produce a signal-on or a signal-off response. Incident photon-to-current conversion efficiency, UV-vis spectroscopy, and flat-band potential measurement indicate that direct transfer of electrons between metallic and semiconductive nanoparticles is responsible for the signal-on response, and incident light absorption and steric hindrance are responsible for the signal-off response. The differential photoelectrochemical signal readout developed here increases the device sensitivity by up to three times compared to a single channel design and demonstrates a limit of detection of 800 aM.

A platinum-nickel bimetallic nanocluster ensemble-on-polyaniline nanofilm for enhanced electrocatalytic oxidation of dopamine.

We report a new approach to design flexible functional material platforms based on electropolymerized polyaniline (PANI) polymer nanofilms modified with bimetallic nanoclusters (NCs) for efficient electro-oxidation of small organic molecules. Composition defined ligand free Pt0.75Ni0.25 NCs were synthesized in the gas phase using the Cluster Beam Deposition (CBD) technology and characterized using RToF, HAADF-STEM, XAFS and XPS. NCs were then directly deposited on PANI coated templates to construct electrodes. Dopamine (DP) molecules were used as a representative organic analyte and the influence of the NC-PANI hybrid atomistic structure on the electrochemical and electrocatalytic performance was investigated. The as prepared, nearly monodispersed, Pt0.75Ni0.25 NCs of ca. 2 nm diameter featuring a PtOx surface combined with a shallow platelet-like Ni-O(OH) phase formed a densely packed active surface on PANI at ultralow metal coverages. Electrochemical measurements (EIS and CV) show a 2.5 times decrease in charge transfer resistance and a remarkable 6-fold increase at lower potential in the mass activity for Pt0.75Ni0.25 NCs in comparison with their pure Pt counterparts. The enhanced electrochemical performance of the Pt0.75Ni0.25 NC hybrid's interface is ascribed to the formation of mixed Pt metal and Ni-O(OH) phases at the surface of the alloyed PtNi cores of the bimetallic NCs under electrochemical conditions combined with an efficient charge conduction pathway between NCs.

Affinity-Based Detection of Biomolecules Using Photo-Electrochemical Readout.

Detection and quantification of biologically-relevant analytes using handheld platforms are important for point-of-care diagnostics, real-time health monitoring, and treatment monitoring. Among the various signal transduction methods used in portable biosensors, photoelectrochemcial (PEC) readout has emerged as a promising approach due to its low limit-of-detection and high sensitivity. For this readout method to be applicable to analyzing native samples, performance requirements beyond sensitivity such as specificity, stability, and ease of operation are critical. These performance requirements are governed by the properties of the photoactive materials and signal transduction mechanisms that are used in PEC biosensing. In this review, we categorize PEC biosensors into five areas based on their signal transduction strategy: (a) introduction of photoactive species, (b) generation of electron/hole donors, (c) use of steric hinderance, (d) in situ induction of light, and (e) resonance energy transfer. We discuss the combination of strengths and weaknesses that these signal transduction systems and their material building blocks offer by reviewing the recent progress in this area. Developing the appropriate PEC biosensor starts with defining the application case followed by choosing the materials and signal transduction strategies that meet the application-based specifications.