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Label-free functional imaging of vagus nerve stimulation-evoked potentials at the cortical surface 皮层表面迷走神经刺激诱发电位的无标记功能成像
Pub Date : 2024-09-10 DOI: 10.1038/s44328-024-00012-z
Laura RoaFiore, Trevor Meyer, Thaissa Peixoto, Pedro Irazoqui
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.
迷走神经刺激(VNS)是美国食品与药物管理局(FDA)批准的一种刺激疗法,用于治疗难治性癫痫患者。在这项工作中,我们使用相干全息成像系统来描述大脑皮层中迷走神经诱发电位(VEP)对 VNS 刺激范式的反应,而无需放置电极或任何遗传、结构或功能标签。我们分析了高达饱和的刺激幅度、高达 800 μs 的脉冲宽度以及从 10 Hz 到 30 Hz 的频率,发现刺激幅度对 VEPs 反应幅度有强烈的调节作用(效应大小为 0.401),而脉冲宽度对诱发电位幅度有适度的调节作用(效应大小为 0.127),频率几乎没有调节作用(效应大小为 0.009)。我们发现脉冲宽度和频率之间存在轻微的相互作用。这种非接触式无标记功能成像技术可作为一种无创快速反馈工具来描述 VEPs,并可提高 VNS 对难治性癫痫患者的疗效。
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引用次数: 0
Towards early diagnosis and screening of Alzheimer’s disease using frequency locked whispering gallery mode microtoroids 利用频率锁定的耳语廊模式微透镜实现阿尔茨海默病的早期诊断和筛查
Pub Date : 2024-08-28 DOI: 10.1038/s44328-024-00009-8
Adley Gin, Phuong-Diem Nguyen, Geidy Serrano, Gene E. Alexander, Judith Su
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.
阿尔茨海默病(AD)是一种以大脑中的淀粉样蛋白斑块和神经纤维缠结为特征的痴呆症。淀粉样蛋白β(Aβ)是一种与这些斑块和缠结有关的阿兹海默病生物标志物。测量 Aβ 的水平有助于早期诊断痴呆症,并有助于药物研究和延缓痴呆症的发生。然而,由于生物流体中的AD生物标记物水平较低,这项工作具有挑战性。在这里,我们使用 FLOWER(频率锁定光学耳语式蒸发共振器)来量化对照组、轻度认知障碍(MCI)组和注意力缺失(AD)组患者死后脑脊液(CSF)中 Aβ42 的水平。FLOWER 可测量微陀螺仪因其蒸发场内折射率变化而产生的共振波长偏移。FLOWER 能测量 CSF Aβ42(曲线下面积,AUC = 0.92),其性能高于 ELISA(AUC = 0.82),并能区分对照组和 MCI 样品。这证明了 FLOWER 能够筛查 CSF 样品以诊断 AD。
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引用次数: 0
Realtime bacteria detection and analysis in sterile liquid products using deep learning holographic imaging 利用深度学习全息成像技术实时检测和分析无菌液体产品中的细菌
Pub Date : 2024-08-23 DOI: 10.1038/s44328-024-00008-9
Nicholas Bravo-Frank, Rushikesh Zende, Lei Feng, Nicolas Mesyngier, Aditya Pachpute, Jiarong Hong
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.
我们介绍了一种结合深度学习(DL)的数字在线全息(DIH)方法,用于实时检测和分析液体悬浮液中的细菌。具体来说,我们设计了一种原型,将 DIH 与荧光成像集成在一起,高效捕捉微流控通道中流动的细菌全息图,利用荧光信号手动识别地面真相进行验证。我们使用定制的 DL 框架处理全息图,该框架包括预处理、检测和分类阶段,涉及在广泛数据集上训练的三个特定 DL 模型,这些数据集包括无菌液体中一般颗粒的全息图,以及具有不同形态、革兰氏染色属性和活力的五种细菌的全息图。通过对合成数据和添加了不同细菌的无菌液体进行实验验证,我们的方法能准确区分细菌和颗粒、活菌和死菌以及形态相似的革兰氏阳性和阴性细菌,同时最大限度地减少误报。这项研究强调了将 DIH 与 DL 结合起来作为临床和工业环境中快速细菌分析的变革性工具的潜力,并有可能扩展到其他应用领域,包括药物筛选、环境监测和疾病诊断。
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引用次数: 0
Functionalization of PEDOT:PSS for aptamer-based sensing of IL6 using organic electrochemical transistors 利用有机电化学晶体管对 PEDOT:PSS 进行功能化,以实现基于适配体的 IL6 检测
Pub Date : 2024-07-24 DOI: 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
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.
在此,我们提出了一种基于聚(乙烯二氧噻吩)-聚(苯乙烯磺酸)(PEDOT:PSS)的有机电化学晶体管(OECTs)的功能化策略,用于感测炎症细胞因子白细胞介素 6(IL6)。为此,我们使用重氮化学方法将 4-aminobenzoic acid 与 PSS 上的磺酸盐分子耦合,后者可作为适配体或其他识别元素(如荧光或氧化还原探针)的锚。我们使用商业丝网印刷 PEDOT:PSS 配方研究了这种方法,同时还研究了 PEDOT 与 PSS 的比例以及其他 PEDOT:PSS 配方中交联剂用量的影响。对于丝网印刷的 OECTs,可以区分缓冲溶液中的 IL6 和牛血清白蛋白 (BSA),并能在牛血浆中检测出纳摩尔范围内的 IL6。此外,与 OECTs 使用的 "标准 "溶液相比,PEDOT:PSS 含量更高的 PEDOT:PSS 配方的功能化与频率相关测量相结合,显示出检测低于 100 pM 的 IL6 浓度的潜力。
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引用次数: 0
Rapid on-site amplification and visual detection of misfolded proteins via microfluidic quaking-induced conversion (Micro-QuIC) 通过微流控震荡诱导转换(Micro-QuIC)对折叠错误的蛋白质进行现场快速扩增和可视检测
Pub Date : 2024-07-24 DOI: 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.
蛋白质错误折叠疾病,如朊病毒病、阿尔茨海默氏症和帕金森氏症,都有一个共同的分子机制,涉及特定蛋白质的错误折叠和聚集。目前迫切需要能准确检测这些错误折叠蛋白质的床旁诊断(POC)技术,以促进早期诊断和干预。在这里,我们介绍了微流体震荡诱导转换(Micro-QuIC),这是一种新型声学流体平台,可用于快速、灵敏地检测蛋白质错误折叠疾病。我们以慢性消耗性疾病(CWD)为模型系统展示了我们技术的实用性,因为野生白尾鹿的样本很容易获得,而且慢性消耗性疾病与人类蛋白质错误折叠疾病有相似之处。声流体混合技术能使试剂在高雷诺数条件下均匀混合,从而大大加快了 CWD 诊断的周转时间。我们的 Micro-QuIC 分析法扩增朊病毒的速度明显快于目前的黄金标准--实时震荡诱导转换(RT-QuIC)。此外,我们还将 Micro-QuIC 与基于金纳米粒子的裸眼检测方法整合在一起,这样就可以目测区分 CWD 阳性样本和 CWD 阴性样本,而无需使用笨重的荧光检测模块。这种集成创建了一个快速的 POC 检测平台,能够检测与各种蛋白质折叠错误疾病相关的折叠错误蛋白质。
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引用次数: 0
Author Correction: Optimal signal quality index for remote photoplethysmogram sensing 作者更正:遥感照相血压计的最佳信号质量指标
Pub Date : 2024-07-17 DOI: 10.1038/s44328-024-00010-1
Mohamed Elgendi, Igor Martinelli, Carlo Menon
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引用次数: 0
Editorial journal inauguration—npj Biosensing 编辑期刊创刊仪式-Npj 生物传感
Pub Date : 2024-06-26 DOI: 10.1038/s44328-024-00005-y
Laura Fabris, Nam-Joon Cho, Hirotsugu Ogi, Cullen Buie, Peter Zijlstra, Sang-Hyun Oh
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引用次数: 0
Advancing cancer detection with portable salivary sialic acid testing 利用便携式唾液唾液酸检测推进癌症检测工作
Pub Date : 2024-06-26 DOI: 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。
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引用次数: 0
Visual detection of misfolded alpha-synuclein and prions via capillary-based quaking-induced conversion assay (Cap-QuIC) 通过毛细管震荡诱导转换测定法(Cap-QuIC)目视检测折叠错误的α-突触核蛋白和朊病毒
Pub Date : 2024-06-26 DOI: 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.
神经退行性蛋白质错误折叠疾病影响着全球数千万人,导致数百万人死亡,并造成多方面的经济困难。据预测,神经退行性疾病的发病率将在未来几十年内大幅上升,但此类疾病的有效诊断方法却十分有限。大多数诊断都是在临床环境中通过观察外部症状得出的,而这些症状通常表现在疾病的相对晚期阶段,因此限制了潜在的治疗应用。虽然生物标志物检测正在取得进展,但其基本方法主要依赖于脆弱而昂贵的设备,这限制了其在医疗点的应用潜力,尤其是在发展中国家。在此,我们介绍基于毛细管的震荡诱导转化(Cap-QuIC),这是一种基于简单毛细管作用的可视化诊断测定,用于检测神经退行性疾病,无需昂贵而复杂的资本设备。通过成功区分与帕金森病(α-突触核蛋白)和慢性消耗性疾病(朊病毒)相关的错误折叠蛋白和健康蛋白,我们证明 Cap-QuIC 有潜力成为检测各种错误折叠蛋白的工具。此外,我们还发现 Cap-QuIC 能够对感染慢性消耗性疾病的野生白尾鹿生物组织样本进行准确分类。我们的研究结果阐明了Cap-QuIC检测法区分错误折叠蛋白的内在机制,凸显了它作为神经退行性疾病诊断技术的潜力。
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引用次数: 0
High-throughput light-induced immunoassay with milliwatt-level laser under one-minute optical antibody-coating on nanoparticle-imprinted substrate 用毫瓦级激光在纳米粒子印迹基底上进行一分钟光学抗体包被,实现高通量光诱导免疫测定
Pub Date : 2024-06-26 DOI: 10.1038/s44328-024-00004-z
Masatoshi Kanoda, Kota Hayashi, Yumiko Takagi, Mamoru Tamura, Shiho Tokonami, Takuya Iida
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.
有效检测蛋白质生物标志物对公共卫生至关重要。然而,传统抗原检测试剂盒的灵敏度相对较低,无法进行早期诊断,实验室免疫测定也需要复杂的预处理过程。如果能将目标纳米材料远程引导到检测部位,就能开发出更简单、更快速的方法。在这里,我们揭示了光诱导免疫测定的机理,即在一分钟内将抗SARS-CoV-2尖峰蛋白抗体涂布在我们开发的纳米粒子印迹质子基底(NPI-PS)亚毫米区域上,并通过使用NPI-PS的两步光学凝结,在几分钟内选择性地检测修饰有尖峰蛋白的纳米粒子,灵敏度可提高一到两个数量级。即使在毫瓦级非共振激光照射下,NPI-PS 也能表现出高性能的光学凝结和高光热特性,从而实现广泛的定量测量。这些发现支持通过高通量检测蛋白质生物标记物来减轻流行病威胁和各种疾病的创新战略。
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引用次数: 0
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