npj BiosensingPub Date : 2026-01-01Epub Date: 2026-05-22DOI: 10.1038/s44328-026-00095-w
Bingchen Wu, Elisa Castagnola, Elaine Robbins, Mariya Kaminsky, Subramaniam Sanker, Colleen A McClung, Xinyan Tracy Cui
{"title":"Tonic dopamine sensing reveals a D2 and D3-mediated dopamine response to raclopride in <i>Clock</i>Δ<i>19</i> mice model.","authors":"Bingchen Wu, Elisa Castagnola, Elaine Robbins, Mariya Kaminsky, Subramaniam Sanker, Colleen A McClung, Xinyan Tracy Cui","doi":"10.1038/s44328-026-00095-w","DOIUrl":"10.1038/s44328-026-00095-w","url":null,"abstract":"<p><p>The circadian rhythm regulates physiological and behavioral processes, with disruptions linked to metabolic and neuropsychiatric disorders. Circadian genes play a crucial role in the regulation of dopaminergic signaling, yet the underlying molecular mechanisms remain unclear. This study investigates how the <i>Clock</i> gene modulates dopamine (DA) dynamics using in vivo electrochemical DA sensing and molecular profiling. Utilizing carbon fiber electrodes (CFEs) with poly(3,4-ethylenedioxythiophene)/carbon nanotube (PEDOT/CNT) coatings, we measured extracellular DA levels in the striatum of wild-type (WT) and <i>Clock</i>Δ<i>19</i> mutant mice via square wave voltammetry (SWV). Pharmacological perturbation with raclopride (D2/D3 receptor antagonist) and nomifensine (DA reuptake inhibitor) revealed an increased DA receptor sensitivity in <i>Clock</i>Δ<i>19</i> mice, with a significantly faster DA response to raclopride. Molecular profiling via qRT-PCR showed elevated <i>tyrosine hydroxylase</i> (<i>TH</i>) expression in the ventral tegmental area (VTA) of <i>Clock</i>Δ<i>19</i> mice, suggesting increased DA synthesis. Additionally, <i>Clock</i>Δ<i>19</i> mice exhibited higher expression of D2 DA receptors and glutamate decarboxylase 67 (Gad67) in the VTA and of D3 DA receptors in the nucleus accumbens (NAc), implicating altered dopaminergic and γ-aminobutyric acid (GABA)ergic regulation. These findings highlight the <i>Clock</i> gene's role in DA homeostasis, revealing its impact on neurotransmission.</p>","PeriodicalId":501705,"journal":{"name":"npj Biosensing","volume":"3 1","pages":"30"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13197223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148019819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
npj BiosensingPub Date : 2026-01-01Epub Date: 2026-04-01DOI: 10.1038/s44328-026-00090-1
Skye Shepherd, Seemesh Bhaskar, Hui Xu, Huimin Zhang, Weinan Liu, Brian T Cunningham
{"title":"Ultrasensitive non-enzymatic protein detection using proximity immunoassay with photonic resonator absorption microscopy.","authors":"Skye Shepherd, Seemesh Bhaskar, Hui Xu, Huimin Zhang, Weinan Liu, Brian T Cunningham","doi":"10.1038/s44328-026-00090-1","DOIUrl":"10.1038/s44328-026-00090-1","url":null,"abstract":"<p><p>Proximity assays have emerged as a leading technology for protein detection, yet broad adoption is currently limited by complex workflows that include enzymatic amplification, thermocycling, and expensive laboratory equipment for signal readout. In this report, we introduce a Proximity Initiated Nucleic Acid Target Amplification (PINATA) assay that is performed at room temperature with a simple two-step, 90-min protocol using a low-cost detection instrument. In contrast to alternative proximity assays, PINATA applies toehold-mediated strand displacement of nucleic acids for enzyme-free reactions that occur at room temperature to uniquely combine linear amplification and digital detection using Photonic Resonator Absorption Microscopy (PRAM). Utilizing human interleukin-6, we demonstrate a detection limit of 37 fg/ml with 6-log dynamic range, high selectivity against non-target cytokines, and assays were performed with complex sample matrices without significant loss of efficacy. We envision that PINATA can address a range of protein quantitation applications for life science research and diagnostics.</p>","PeriodicalId":501705,"journal":{"name":"npj Biosensing","volume":"3 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13186449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147984889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Regional variations in seeding activity, phosphorylation, and protein levels of tau in Alzheimer’s disease brain","authors":"Yirong Yang, Huiying Guan, Zihao Zhang, Hailun Wu, Ying Xiong, Can Xu, Hengxu Mao, Wuxin You, Yaoyun Kuang, Qi‐Lei Zhang, Hancun Yi, Mengting Li, Yuhai Gu, Chengsi Wu, Kuan Ning, Pengcheng Huang, Xiao‐Xin Yan, Ansgar Poetsch, Yang Shi, Zhong Pei, Pingyi Xu, Yue Huang, Daojun Hong, Wen‐Quan Zou","doi":"10.1038/s44328-025-00056-9","DOIUrl":"https://doi.org/10.1038/s44328-025-00056-9","url":null,"abstract":"In Alzheimer’s disease (AD), hyperphosphorylated tau propagates across brain regions through its seeding activity, much like prions. We assessed regional tau seeding activity and phosphorylation by RT-QuIC, western blotting (WB), and mass spectrometry in entorhinal cortex (ENT), inferior/middle/superior temporal gyri (ITG/MTG/STG), and cerebellum (CER). Tau-seeding was highest in ENT among the brain regions examined and correlated positively with Braak staging. AD-derived RT-QuIC products formed tau fibrils, propagating intracellularly in cell models. WB showed significantly higher pTau217/pTau396 in ITG vs. STG/CER. Seeding-activity correlated with WB levels of pTau217/pTau262/pTau396 (p = 0.004, p = 0.0028, p = 0.003) and Braak/Thal staging in temporal regions. Anti-tau antibodies varied in immunodepleting seeding (pTau217 > TAU5 > pTau181 > pTau396). Mass spectrometry identified 11 phospho-sites in ITG tau, while pTau231/pTau262/pTau263/pTau396 were AD-specific. Regional tau-seeding correlates with local phospho-tau levels and pathology, supporting plasma pTau217 for diagnosis and seeding activity as a potential biomarker.","PeriodicalId":501705,"journal":{"name":"npj Biosensing","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44328-025-00056-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147903919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
npj BiosensingPub Date : 2025-01-01Epub Date: 2025-01-16DOI: 10.1038/s44328-024-00018-7
Annie Yang-Schulz, Maria Zacharopoulou, Sema Zeynep Yilmaz, Anupam Banerjee, Satyaki Saha, Daniel Nietlispach, Michael Ohlmeyer, Mert Gur, Laura S Itzhaki, Ivet Bahar, Reuven Gordon
{"title":"Direct observation of small molecule activator binding to single PR65 protein.","authors":"Annie Yang-Schulz, Maria Zacharopoulou, Sema Zeynep Yilmaz, Anupam Banerjee, Satyaki Saha, Daniel Nietlispach, Michael Ohlmeyer, Mert Gur, Laura S Itzhaki, Ivet Bahar, Reuven Gordon","doi":"10.1038/s44328-024-00018-7","DOIUrl":"10.1038/s44328-024-00018-7","url":null,"abstract":"<p><p>The reactivation of heterotrimeric protein phosphatase 2A (PP2A) through small molecule activators is of interest to therapeutic intervention due to its dysregulation, which is linked to chronic conditions. This study focuses on the PP2A scaffold subunit PR65 and a small molecule activator, ATUX-8385, designed to bind directly to this subunit. Using a label-free single-molecule approach with nanoaperture optical tweezers (NOT), we quantify its binding, obtaining a dissociation constant of 13.6 ± 2.5 μM, consistent with ensemble fluorescence anisotropy results but challenging to achieve with other methods due to low affinity. Single-molecule NOT measurements reveal that binding increases optical scattering, indicating PR65 elongation. This interpretation is supported by all-atom molecular dynamics simulations showing PR65 adopts more extended conformations upon binding. This work highlights NOT's utility in quantifying binding kinetics and structural impact, offering insights valuable for drug discovery.</p>","PeriodicalId":501705,"journal":{"name":"npj Biosensing","volume":"2 1","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11738983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
npj BiosensingPub Date : 2025-01-01Epub Date: 2025-01-31DOI: 10.1038/s44328-024-00021-y
David A M Colburn, Terry L Chern, Vincent E Guo, Kennedy A Salamat, Daniel N Pugliese, Corey K Bradley, Daichi Shimbo, Samuel K Sia
{"title":"A method for blood pressure hydrostatic pressure correction using wearable inertial sensors and deep learning.","authors":"David A M Colburn, Terry L Chern, Vincent E Guo, Kennedy A Salamat, Daniel N Pugliese, Corey K Bradley, Daichi Shimbo, Samuel K Sia","doi":"10.1038/s44328-024-00021-y","DOIUrl":"10.1038/s44328-024-00021-y","url":null,"abstract":"<p><p>Cuffless noninvasive blood pressure (BP) measurement could enable early unobtrusive detection of abnormal BP patterns, but when the sensor is placed on a location away from heart level (such as the arm), its accuracy is compromised by variations in the position of the sensor relative to heart level; such positional variations produce hydrostatic pressure changes that can cause swings in tens of mmHg in the measured BP if uncorrected. A standard method to correct for changes in hydrostatic pressure makes use of a bulky fluid-filled tube connecting heart level to the sensor. Here, we present an alternative method to correct for variations in hydrostatic pressure using unobtrusive wearable inertial sensors. This method, called IMU-Track, analyzes motion information with a deep learning model; for sensors placed on the arm, IMU-Track calculates parameterized arm-pose coordinates, which are then used to correct the measured BP. We demonstrated IMU-Track for BP measurements derived from pulse transit time, acquired using electrocardiography and finger photoplethysmography, with validation data collected across 20 participants. Across these participants, for the hand heights of 25 cm below or above the heart, mean absolute errors were reduced for systolic BP from 13.5 ± 1.1 and 9.6 ± 1.1 to 5.9 ± 0.7 and 5.9 ± 0.5 mmHg, respectively, and were reduced for diastolic BP from 15.0 ± 1.0 and 11.5 ± 1.5 to 6.8 ± 0.5 and 7.8 ± 0.8, respectively. On a commercial smartphone, the arm-tracking inference time was ~134 ms, sufficiently fast for real-time hydrostatic pressure correction. This method for correcting hydrostatic pressure may enable accurate passive cuffless BP monitors placed at positions away from heart level that accommodate everyday movements.</p>","PeriodicalId":501705,"journal":{"name":"npj Biosensing","volume":"2 1","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
npj BiosensingPub Date : 2025-01-01Epub Date: 2025-05-02DOI: 10.1038/s44328-025-00038-x
Cameron Gilroy, Callum D Silver, Casper Kunstmann-Olsen, Lisa M Miller, Steven D Johnson, Thomas F Krauss
{"title":"A passive blood separation sensing platform for point-of-care devices.","authors":"Cameron Gilroy, Callum D Silver, Casper Kunstmann-Olsen, Lisa M Miller, Steven D Johnson, Thomas F Krauss","doi":"10.1038/s44328-025-00038-x","DOIUrl":"https://doi.org/10.1038/s44328-025-00038-x","url":null,"abstract":"<p><p>The blood test is one of the most performed investigations in clinical practice, with samples typically analysed in a centralised laboratory. Many of these tests monitor routine conditions that would benefit from a point-of-care approach, reducing the burden on practitioners, patients and healthcare systems. Such a decentralised model requires the development of sophisticated, yet easy-to-use technology; however, platforms that combine high-performance with low-cost and simplicity remain scarce. Moreover, most research papers only address a subset of requirements and study specific aspects in isolation. A systems approach that considers the interplay between each element of the technology is clearly required to develop a coherent solution. Here, we present such a systems approach in the context of testing for C-reactive protein (CRP), a commonly requested test in clinical practise that indicates inflammation and is particularly relevant for monitoring patients with chronic diseases, e.g. those with rheumatoid arthritis or who are undergoing cancer therapy. The approach we take here features an entirely passive microfluidic cartridge for blood separation, integrated with a high-performance sensing platform which we have tested in a real-world context. The device is compatible with a handheld detection unit and is simple to use yet can accurately detect CRP levels at clinically relevant levels.</p>","PeriodicalId":501705,"journal":{"name":"npj Biosensing","volume":"2 1","pages":"19"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metabolite microextraction on surface-enhanced Raman scattering nanofibres and D<sub>2</sub>O probing accelerate antibiotic susceptibility testing.","authors":"Malama Chisanga, Claudèle Lemay-St-Denis, Xinran Wei, Yuzhang Liang, Mengdi Lu, Wei Peng, Joelle N Pelletier, Jean-Francois Masson","doi":"10.1038/s44328-025-00039-w","DOIUrl":"10.1038/s44328-025-00039-w","url":null,"abstract":"<p><p>Rapid antibiotic susceptibility tests (AST) are vital for the effective treatment of disease, necessitating the development of analytical tools to address unmet needs in healthcare. Leveraging the sensitivity of plasmonic nanosensors and isotopic labelling has the potential to accelerate AST. Here, we developed surface-enhanced Raman scattering (SERS)-based nanofibre sensors and heavy water [deuterium oxide (D<sub>2</sub>O)] labelling (SERS-DIP) for detecting the minimum inhibitory concentration (MIC) and AST for trimethoprim (TMP) against <i>E. coli</i>. SERS-DIP rapidly detected the MIC of TMP for the susceptible strain in 2 h. TMP-resistant cells retained the metabolic activity regardless of TMP levels, confirming the resistance phenotype. Kinetic analysis of D uptake by resistant cells treated with TMP (2 × MIC) revealed increasing D levels proportional to peak redshifts over time, confirmed by machine learning-driven data exploration. Our results demonstrate the utility of nanofibre-enabled SERS-DIP for robust AST, uncovering new spectral biomarkers that may impact clinical medicine.</p>","PeriodicalId":501705,"journal":{"name":"npj Biosensing","volume":"2 1","pages":"21"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12129813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
npj BiosensingPub Date : 2025-01-01Epub Date: 2025-05-02DOI: 10.1038/s44328-025-00040-3
Khuong Duy Mac, Judith Su
{"title":"Optical biosensors for diagnosing neurodegenerative diseases.","authors":"Khuong Duy Mac, Judith Su","doi":"10.1038/s44328-025-00040-3","DOIUrl":"10.1038/s44328-025-00040-3","url":null,"abstract":"<p><p>Neurodegenerative diseases involve the progressive loss of neurons in the brain and nervous system, leading to functional decline. Early detection is critical for improving outcomes and advancing therapies. Optical biosensors, some of which offer rapid, label-free, and ultra-sensitive detection, have been applied to early diagnosis and drug screening. This review examines the principles and performance of different optical biosensors used for diagnosing neurodegenerative diseases and discusses potential future advancements.</p>","PeriodicalId":501705,"journal":{"name":"npj Biosensing","volume":"2 1","pages":"20"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
npj BiosensingPub Date : 2025-01-01Epub Date: 2025-02-21DOI: 10.1038/s44328-025-00033-2
Steven M Quarin, Der Vang, Ruxandra I Dima, George Stan, Pietro Strobbia
{"title":"AI in SERS sensing moving from discriminative to generative.","authors":"Steven M Quarin, Der Vang, Ruxandra I Dima, George Stan, Pietro Strobbia","doi":"10.1038/s44328-025-00033-2","DOIUrl":"10.1038/s44328-025-00033-2","url":null,"abstract":"<p><p>This perspective discusses the present and future role of artificial intelligence (AI) and machine learning (ML) in surface-enhanced Raman scattering (SERS) sensing. Our goal is to guide the reader through current applications, mainly focused on discriminative approaches aimed at developing new and improved SERS diagnostic capabilities, towards the future role of AI in SERS sensing, with the use of generative approaches to design new materials and biomaterials.</p>","PeriodicalId":501705,"journal":{"name":"npj Biosensing","volume":"2 1","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11845314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
npj BiosensingPub Date : 2025-01-01Epub Date: 2025-11-07DOI: 10.1038/s44328-025-00057-8
Srishti Johri, Dennis Chan, Roslyn S Massey, Daniel Knight, Maria C DeRosa, Matthew R Holahan, Ravi Prakash
{"title":"Organic electrolyte gated field effect transistor for detecting alpha synuclein longitudinally in Parkinsonism mouse model.","authors":"Srishti Johri, Dennis Chan, Roslyn S Massey, Daniel Knight, Maria C DeRosa, Matthew R Holahan, Ravi Prakash","doi":"10.1038/s44328-025-00057-8","DOIUrl":"10.1038/s44328-025-00057-8","url":null,"abstract":"<p><p>Parkinson's Disease (PD) is an age-progressive disorder caused by misfolding of alpha-synuclein (α-Syn) that can begin years before clinical symptoms appear, making early diagnosis crucial for timely intervention. In this study, a novel antibody-functionalized Organic Electrolyte-Gated Field-Effect-Transistor (Ab-OEGFET) biosensor was implemented to detect α-Syn levels in blood serum samples from an A53T Transgenic (TG) mouse line. PD-like pathology was examined in blood serum using Ab-OEGFET devices and in brain tissue samples using Western Blot and immunohistochemistry. Different forms (monomeric, phosphorylated, oligomeric) of α-Syn were identified in low volumes of blood serum samples collected from TG and Wild Type (WT) populations of mice at ages 2, 5 and 8 months, and the biosensor response was correlated to Blot and immunohistochemistry results. The Ab-OEGFETs performance in this study is a promising result towards a minimally invasive blood biomarker-based multianalyte testing strategy for early screening of PD and similar neurodegenerative disease pathologies.</p>","PeriodicalId":501705,"journal":{"name":"npj Biosensing","volume":"2 1","pages":"39"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12594612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145484445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}