Digital immunoassay for biomarker concentration quantification using solid-state nanopores.
Digital immunoassay for biomarker concentration quantification using solid-state nanopores.
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DOI：
10.1038/s41467-021-25566-8
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发表时间：
2021-09-09
影响因子：
16.6
通讯作者：
Tabard-Cossa V
中科院分区：
文献类型：
--
作者：
He L;Tessier DR;Briggs K;Tsangaris M;Charron M;McConnell EM;Lomovtsev D;Tabard-Cossa V
单分子计数是确定溶液中生物标记物浓度的最准确和最精确的方法，并导致了能够实现精确医学的数字诊断平台的出现。原则上，固态纳米孔--具有单分子灵敏度的全电子传感器--非常适合这项任务。在这里，我们提出了一种数字免疫分析方案，能够可靠地定量复杂生物液中的目标蛋白质浓度，克服了使用固态纳米孔进行蛋白质传感所带来的特异性、敏感性和一致性挑战。这是通过使用易于识别的DNA纳米结构作为通过磁珠夹心免疫分析捕获的目标蛋白的存在(“1”)或不存在(“0”)的替代来实现的。作为概念验证，我们展示了从人类血清样本到高分子范围的促甲状腺激素浓度的量化。对该方法的进一步优化将提高灵敏度和动态范围，从而允许开发与护理点格式兼容的精密诊断工具。生物标志物在溶液中的浓度可以通过计数单分子来确定。在这里，作者报告了一种数字免疫分析方案，该方案使用固态纳米孔读数来量化目标蛋白，并使用该方案来测量人血清中的促甲状腺激素。
Single-molecule counting is the most accurate and precise method for determining the concentration of a biomarker in solution and is leading to the emergence of digital diagnostic platforms enabling precision medicine. In principle, solid-state nanopores—fully electronic sensors with single-molecule sensitivity—are well suited to the task. Here we present a digital immunoassay scheme capable of reliably quantifying the concentration of a target protein in complex biofluids that overcomes specificity, sensitivity, and consistency challenges associated with the use of solid-state nanopores for protein sensing. This is achieved by employing easily-identifiable DNA nanostructures as proxies for the presence (“1”) or absence (“0”) of the target protein captured via a magnetic bead-based sandwich immunoassay. As a proof-of-concept, we demonstrate quantification of the concentration of thyroid-stimulating hormone from human serum samples down to the high femtomolar range. Further optimization to the method will push sensitivity and dynamic range, allowing for development of precision diagnostic tools compatible with point-of-care format. The concentration of a biomarker in solution can be determined by counting single molecules. Here the authors report a digital immunoassay scheme with solid-state nanopore readout to quantify a target protein and use this to measure thyroid-stimulating hormone from human serum.
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影响因子：
10.8
作者：
Briggs K;Madejski G;Magill M;Kastritis K;de Haan HW;McGrath JL;Tabard-Cossa V
通讯作者：
Tabard-Cossa V
DOI：
10.1073/pnas.1205004109
发表时间：
2012-07-10
影响因子：
11.1
作者：
Bercovici, Moran;Han, Crystal M.;Santiago, Juan G.
通讯作者：
Santiago, Juan G.
影响因子：
8.9
作者：
Beamish, Eric;Tabard-Cossa, Vincent;Godin, Michel
通讯作者：
Godin, Michel
影响因子：
16.6
作者：
Cai, Shenglin;Sze, Jasmine Y. Y.;Edel, Joshua B.
通讯作者：
Edel, Joshua B.
影响因子：
10.8
作者：
Chen, Kaikai;Kong, Jinglin;Keyser, Ulrich F.
通讯作者：
Keyser, Ulrich F.