npj BiosensingPub Date : 2024-09-10DOI: 10.1038/s44328-024-00012-z
Laura RoaFiore, Trevor Meyer, Thaissa Peixoto, Pedro Irazoqui
{"title":"Label-free functional imaging of vagus nerve stimulation-evoked potentials at the cortical surface","authors":"Laura RoaFiore, Trevor Meyer, Thaissa Peixoto, Pedro Irazoqui","doi":"10.1038/s44328-024-00012-z","DOIUrl":"10.1038/s44328-024-00012-z","url":null,"abstract":"Vagus nerve stimulation (VNS) is an FDA-approved stimulation therapy to treat patients with refractory epilepsy. In this work, we use a coherent holographic imaging system to characterize vagus nerve-evoked potentials (VEPs) in the cortex in response to VNS stimulation paradigms without electrode placement or any genetic, structural, or functional labels. We analyze stimulation amplitude up to saturation, pulse width up to 800 μs, and frequency from 10 Hz to 30 Hz, finding that stimulation amplitude strongly modulates VEPs response magnitude (effect size 0.401), while pulse width has a moderate modulatory effect (effect size 0.127) and frequency has almost no modulatory effect (effect size 0.009) on the evoked potential magnitude. We find mild interactions between pulse width and frequency. This non-contact label-free functional imaging technique may serve as a non-invasive rapid-feedback tool to characterize VEPs and may increase the efficacy of VNS in patients with refractory epilepsy.","PeriodicalId":501705,"journal":{"name":"npj Biosensing","volume":" ","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44328-024-00012-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160263","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 : 2024-08-28DOI: 10.1038/s44328-024-00009-8
Adley Gin, Phuong-Diem Nguyen, Geidy Serrano, Gene E. Alexander, Judith Su
{"title":"Towards early diagnosis and screening of Alzheimer’s disease using frequency locked whispering gallery mode microtoroids","authors":"Adley Gin, Phuong-Diem Nguyen, Geidy Serrano, Gene E. Alexander, Judith Su","doi":"10.1038/s44328-024-00009-8","DOIUrl":"10.1038/s44328-024-00009-8","url":null,"abstract":"Alzheimer’s disease (AD) is a form of dementia marked by amyloid plaques and neurofibrillary tangles in the brain. Amyloid beta (Aβ) is an AD biomarker which is linked to these plaques and tangles. Measuring Aβ levels can help with early AD diagnosis and aid in drug studies and delaying dementia. This is challenging, however, due to low AD biomarker levels in biofluids. Here we use FLOWER (frequency-locked optical whispering evanescent resonator) to quantify levels of post-mortem cerebrospinal fluid (CSF) Aβ42 in control, mild cognitive impairment (MCI), and AD participants. FLOWER measures the resonant wavelength shift of a microtoroid due to changes in the refractive index within its evanescent field. FLOWER can measure CSF Aβ42 (area under curve, AUC = 0.92) with higher performance than ELISA (AUC = 0.82) and can distinguish between control and MCI samples. This demonstrates FLOWER’s ability to screen CSF samples for diagnosis of AD.","PeriodicalId":501705,"journal":{"name":"npj Biosensing","volume":" ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44328-024-00009-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142084616","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 : 2024-08-23DOI: 10.1038/s44328-024-00008-9
Nicholas Bravo-Frank, Rushikesh Zende, Lei Feng, Nicolas Mesyngier, Aditya Pachpute, Jiarong Hong
{"title":"Realtime bacteria detection and analysis in sterile liquid products using deep learning holographic imaging","authors":"Nicholas Bravo-Frank, Rushikesh Zende, Lei Feng, Nicolas Mesyngier, Aditya Pachpute, Jiarong Hong","doi":"10.1038/s44328-024-00008-9","DOIUrl":"10.1038/s44328-024-00008-9","url":null,"abstract":"We introduce a digital inline holography (DIH) method combined with deep learning (DL) for real-time detection and analysis of bacteria in liquid suspension. Specifically, we designed a prototype that integrates DIH with fluorescence imaging to efficiently capture holograms of bacteria flowing in a microfluidic channel, utilizing the fluorescent signal to manually identify ground truths for validation. We process holograms using a tailored DL framework that includes preprocessing, detection, and classification stages involving three specific DL models trained on an extensive dataset that included holograms of generic particles present in sterile liquid and five bacterial species featuring distinct morphologies, Gram stain attributes, and viability. Our approach, validated through experiments with synthetic data and sterile liquid spiked with different bacteria, accurately distinguishes between bacteria and particles, live and dead bacteria, and Gram-positive and negative bacteria of similar morphology, all while minimizing false positives. The study highlights the potential of combining DIH with DL as a transformative tool for rapid bacterial analysis in clinical and industrial settings, with potential extension to other applications including pharmaceutical screening, environmental monitoring, and disease diagnostics.","PeriodicalId":501705,"journal":{"name":"npj Biosensing","volume":" ","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44328-024-00008-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142041759","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 : 2024-07-24DOI: 10.1038/s44328-024-00007-w
Bernhard Burtscher, Chiara Diacci, Anatolii Makhinia, Marios Savvakis, Erik O. Gabrielsson, Lothar Veith, Xianjie Liu, Xenofon Strakosas, Daniel T. Simon
{"title":"Functionalization of PEDOT:PSS for aptamer-based sensing of IL6 using organic electrochemical transistors","authors":"Bernhard Burtscher, Chiara Diacci, Anatolii Makhinia, Marios Savvakis, Erik O. Gabrielsson, Lothar Veith, Xianjie Liu, Xenofon Strakosas, Daniel T. Simon","doi":"10.1038/s44328-024-00007-w","DOIUrl":"10.1038/s44328-024-00007-w","url":null,"abstract":"Here we propose a strategy to functionalize poly(ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) based organic electrochemical transistors (OECTs) for sensing the inflammatory cytokine interleukin 6 (IL6). For this aim we use diazonium chemistry to couple 4-aminobenzoic acid to sulfonate moieties on the PSS, which can act as anchors for aptamers or other recognition elements (e.g., fluorescent, or redox probes). We investigated this approach with a commercial screen-printable PEDOT:PSS formulation but also studied the effect of PEDOT to PSS ratio as well as the amount of crosslinker in other PEDOT:PSS formulations. For screen printed OECTs, it was possible to distinguish between IL6 and bovine serum albumin (BSA) in buffer solution and detect IL6 when added in bovine plasma in the nanomolar range. Furthermore, functionalization of PEDOT:PSS formulations with higher PSS content (compared to the “standard” solutions used for OECTs) combined with frequency dependent measurements showed the potential to detect IL6 concentrations below 100 pM.","PeriodicalId":501705,"journal":{"name":"npj Biosensing","volume":" ","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44328-024-00007-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141810110","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 : 2024-07-24DOI: 10.1038/s44328-024-00006-x
Dong Jun Lee, Peter R. Christenson, Gage Rowden, Nathan C. Lindquist, Peter A. Larsen, Sang-Hyun Oh
{"title":"Rapid on-site amplification and visual detection of misfolded proteins via microfluidic quaking-induced conversion (Micro-QuIC)","authors":"Dong Jun Lee, Peter R. Christenson, Gage Rowden, Nathan C. Lindquist, Peter A. Larsen, Sang-Hyun Oh","doi":"10.1038/s44328-024-00006-x","DOIUrl":"10.1038/s44328-024-00006-x","url":null,"abstract":"Protein misfolding diseases, such as prion diseases, Alzheimer’s, and Parkinson’s, share a common molecular mechanism involving the misfolding and aggregation of specific proteins. There is an urgent need for point-of-care (POC) diagnostic technologies that can accurately detect these misfolded proteins, facilitating early diagnosis and intervention. Here, we introduce the microfluidic quaking-induced conversion (Micro-QuIC), a novel acoustofluidic platform for the rapid and sensitive detection of protein misfolding diseases. We demonstrate the utility of our technology using chronic wasting disease (CWD) as a model system, since samples from wild white-tailed deer are readily accessible, and CWD shares similarities with human protein misfolding diseases. Acoustofluidic mixing enables homogeneous mixing of reagents in a high-Reynolds-number regime, significantly accelerating the turnaround time for CWD diagnosis. Our Micro-QuIC assay amplifies prions significantly faster than the current gold standard, real-time quaking-induced conversion (RT-QuIC). Furthermore, we integrated Micro-QuIC with a gold nanoparticle-based, naked-eye detection method, which enables visual discrimination between CWD-positive and CWD-negative samples without the need for a bulky fluorescence detection module. This integration creates a rapid, POC testing platform capable of detecting misfolded proteins associated with a variety of protein misfolding diseases.","PeriodicalId":501705,"journal":{"name":"npj Biosensing","volume":" ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44328-024-00006-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141810190","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 : 2024-06-26DOI: 10.1038/s44328-024-00001-2
Mohamed Elgendi, Lynnette Lyzwinski, Eric Kübler, Alexander V. Shokurov, Newton Howard, Carlo Menon
{"title":"Advancing cancer detection with portable salivary sialic acid testing","authors":"Mohamed Elgendi, Lynnette Lyzwinski, Eric Kübler, Alexander V. Shokurov, Newton Howard, Carlo Menon","doi":"10.1038/s44328-024-00001-2","DOIUrl":"10.1038/s44328-024-00001-2","url":null,"abstract":"This perspective emphasizes the robust evidence supporting salivary sialic acid (SA) as a valuable tool for cancer prescreening, particularly for oral and breast cancers. The potential benefits of salivary SA testing include early cancer detection and treatment response monitoring. The challenges and opportunities of developing a portable cancer detection device are discussed. Enabling accessible and timely prescreening through salivary SA testing has the potential to save lives and offer an alternative to mammograms for low-risk groups. Portable Raman spectrometers show promise for SA analysis, but cost and sensitivity challenges need attention. The potential for personalized medicine, multiplexing capabilities, and remote collaboration further enhances the value of portable Raman-based cancer detection devices. Implementing these recommendations may lead to the future use of portable devices in cancer detection through salivary SA analysis. Salivary SA’s promising potential as a prescreening or adjunct biomarker extends beyond the clinical setting, and its integration into routine practice could empower individuals for home-based cancer detection, enabling more convenient and effective health monitoring.","PeriodicalId":501705,"journal":{"name":"npj Biosensing","volume":" ","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44328-024-00001-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489062","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 : 2024-06-26DOI: 10.1038/s44328-024-00003-0
Peter R. Christenson, Hyeonjeong Jeong, Hyerim Ahn, Manci Li, Gage Rowden, Rachel L. Shoemaker, Peter A. Larsen, Hye Yoon Park, Sang-Hyun Oh
{"title":"Visual detection of misfolded alpha-synuclein and prions via capillary-based quaking-induced conversion assay (Cap-QuIC)","authors":"Peter R. Christenson, Hyeonjeong Jeong, Hyerim Ahn, Manci Li, Gage Rowden, Rachel L. Shoemaker, Peter A. Larsen, Hye Yoon Park, Sang-Hyun Oh","doi":"10.1038/s44328-024-00003-0","DOIUrl":"10.1038/s44328-024-00003-0","url":null,"abstract":"Neurodegenerative protein misfolding diseases impact tens of millions of people worldwide, contributing to millions of deaths and economic hardships across multiple scales. The prevalence of neurodegenerative disease is predicted to greatly increase over the coming decades, yet effective diagnostics for such diseases are limited. Most diagnoses come from the observation of external symptoms in clinical settings, which typically manifest during relatively advanced stages of disease, thus limiting potential therapeutic applications. While progress is being made on biomarker testing, the underlying methods largely rely on fragile and expensive equipment that limits their point-of-care potential, especially in developing countries. Here we present Capillary-based Quaking Induced Conversion (Cap-QuIC) as a visual diagnostic assay based on simple capillary action for the detection of neurodegenerative disease without necessitating expensive and complex capital equipment. We demonstrate that Cap-QuIC has the potential to be a detection tool for a broad range of misfolded proteins by successfully distinguishing misfolded versus healthy proteins associated with Parkinson’s disease (α-synuclein) and Chronic Wasting Disease (prions). Additionally, we show that Cap-QuIC can accurately classify biological tissue samples from wild white-tailed deer infected with Chronic Wasting Disease. Our findings elucidate the underlying mechanism that enables the Cap-QuIC assay to distinguish misfolded protein, highlighting its potential as a diagnostic technology for neurodegenerative diseases.","PeriodicalId":501705,"journal":{"name":"npj Biosensing","volume":" ","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44328-024-00003-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489095","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":"High-throughput light-induced immunoassay with milliwatt-level laser under one-minute optical antibody-coating on nanoparticle-imprinted substrate","authors":"Masatoshi Kanoda, Kota Hayashi, Yumiko Takagi, Mamoru Tamura, Shiho Tokonami, Takuya Iida","doi":"10.1038/s44328-024-00004-z","DOIUrl":"10.1038/s44328-024-00004-z","url":null,"abstract":"The efficient detection of protein biomarkers is critical for public health. However, the sensitivity of conventional antigen test kits is relatively low for early diagnosis, and laboratory immunoassays require complex pretreatment processes overnight. If target nanomaterials could be remotely guided to the detection site, simpler and faster methods would be developed. Here, we reveal the mechanism of light-induced immunoassay that anti-spike-protein antibodies for SARS-CoV-2 were coated on our developed nanoparticle-imprinted plasmonic substrate (NPI-PS) over the submillimeter area within one minute and nanoparticles modified with spike proteins can be selectively detected within a few minutes at one or two orders of higher sensitivity via a two-step optical condensation using NPI-PS. NPI-PS exhibits high-performance optical condensation with high photothermal properties even under milliwatt-class nonresonant laser irradiation, enabling a wide range of quantitative measurements. These findings support an innovative strategy to mitigate pandemic threats and various diseases through the high-throughput detection of protein biomarkers.","PeriodicalId":501705,"journal":{"name":"npj Biosensing","volume":" ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44328-024-00004-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489064","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}