Pub 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
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.
{"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}
Pub Date : 2024-06-26DOI: 10.1038/s44328-024-00001-2
Mohamed Elgendi, Lynnette Lyzwinski, Eric Kübler, Alexander V. Shokurov, Newton Howard, Carlo Menon
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.
这一观点强调了唾液唾液酸（SA）作为癌症预检，尤其是口腔癌和乳腺癌预检的重要工具的有力证据。唾液唾液酸检测的潜在益处包括早期癌症检测和治疗反应监测。本文讨论了开发便携式癌症检测设备所面临的挑战和机遇。通过唾液SA检测实现方便、及时的预检有可能挽救生命，并为低风险人群提供乳房X光检查的替代方法。便携式拉曼光谱仪在唾液酸分析方面大有可为，但需要注意成本和灵敏度方面的挑战。个性化医疗、多路复用能力和远程协作的潜力进一步提升了便携式拉曼癌症检测设备的价值。落实这些建议可使便携式设备在未来通过唾液 SA 分析进行癌症检测。唾液SA作为预筛或辅助生物标志物的潜力远不止于临床环境，将其整合到日常实践中可增强个人在家中进行癌症检测的能力，从而实现更方便、更有效的健康监测。
{"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}
Pub 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
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.
{"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}
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.
{"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}
Pub Date : 2024-06-26DOI: 10.1038/s44328-024-00002-1
Mohamed Elgendi, Igor Martinelli, Carlo Menon
Remote photoplethysmography (rPPG) enables non-invasive monitoring of circulatory signals using mobile devices, a crucial advancement in biosensing. Despite its potential, ensuring signal quality amidst noise and artifacts remains a significant challenge, particularly in healthcare applications. Addressing this, our study focuses on a singular signal quality index (SQI) for rPPG, aimed at simplifying high-quality video capture for heart rate detection and cardiac assessment. We introduce a practical threshold for this SQI, specifically the signal-to-noise ratio index (NSQI), optimized for straightforward implementation on portable devices for real-time video analysis. Employing (NSQI < 0.293) as our threshold, our methodology successfully identifies high-quality cardiac information in video frames, effectively mitigating the influence of noise and artifacts. Validated on publicly available datasets with advanced machine learning algorithms and leave-one-out cross-validation, our approach significantly reduces computational complexity. This innovation not only enhances efficiency in health monitoring applications but also offers a pragmatic solution for remote biosensing. Our findings constitute a notable advancement in rPPG signal quality assessment, marking a critical step forward in the development of remote cardiac monitoring technologies with extensive healthcare implications.
{"title":"Optimal signal quality index for remote photoplethysmogram sensing","authors":"Mohamed Elgendi, Igor Martinelli, Carlo Menon","doi":"10.1038/s44328-024-00002-1","DOIUrl":"10.1038/s44328-024-00002-1","url":null,"abstract":"Remote photoplethysmography (rPPG) enables non-invasive monitoring of circulatory signals using mobile devices, a crucial advancement in biosensing. Despite its potential, ensuring signal quality amidst noise and artifacts remains a significant challenge, particularly in healthcare applications. Addressing this, our study focuses on a singular signal quality index (SQI) for rPPG, aimed at simplifying high-quality video capture for heart rate detection and cardiac assessment. We introduce a practical threshold for this SQI, specifically the signal-to-noise ratio index (NSQI), optimized for straightforward implementation on portable devices for real-time video analysis. Employing (NSQI < 0.293) as our threshold, our methodology successfully identifies high-quality cardiac information in video frames, effectively mitigating the influence of noise and artifacts. Validated on publicly available datasets with advanced machine learning algorithms and leave-one-out cross-validation, our approach significantly reduces computational complexity. This innovation not only enhances efficiency in health monitoring applications but also offers a pragmatic solution for remote biosensing. Our findings constitute a notable advancement in rPPG signal quality assessment, marking a critical step forward in the development of remote cardiac monitoring technologies with extensive healthcare implications.","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/s44328-024-00002-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141489093","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}
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