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手持式拉曼光谱仪在定量结核病生物标志物检测中的仪器性能评估:用于即时感染性疾病诊断的性能评估。

Handheld Raman Spectrometer Instrumentation for Quantitative Tuberculosis Biomarker Detection: A Performance Assessment for Point-of-Need Infectious Disease Diagnostics.

机构信息

1 Department of Chemistry, University of Utah, Salt Lake City, UT, USA.

2 Nano Institute of Utah, University of Utah, Salt Lake City, UT, USA.

出版信息

Appl Spectrosc. 2018 Jul;72(7):1104-1115. doi: 10.1177/0003702818770666. Epub 2018 Apr 17.

DOI:10.1177/0003702818770666
PMID:29664331
Abstract

Techniques for the detection of disease biomarkers are key components in the protection of human health. While work over the last few decades has redefined the low-level measurement of disease biomarkers, the translation of these capabilities from the formal clinical setting to point-of-need (PON) usage has been much more limited. This paper presents the results of experiments designed to examine the potential utility of a handheld Raman spectrometer as a PON electronic reader for a sandwich immunoassay based on surface-enhanced Raman scattering (SERS). In so doing, the study herein used a recently developed procedure for the SERS detection of phospho-myo-inositol-capped lipoarabinomannan (PILAM) as a means to compare the performance of laboratory-grade and handheld instrumentation and, therefore, gauge the utility of the handheld instrument for PON deployment. Phospho-myo-inositol-capped lipoarabinomannan is a non-pathogenic simulant for mannose-capped lipoarabinomannan (ManLAM), which is an antigenic marker found in serum and other body fluids of individuals infected with tuberculosis (TB). The results of the measurements with the field-portable spectrometer were then compared to those obtained for the same samples when using a much more sensitive benchtop Raman spectrometer. The results, albeit under different operational settings for the two spectrometers (e.g., signal integration time), are promising in that the limit of detection found for PILAM spiked in human serum when using the handheld system (0.18 ng/mL) approached that of the benchtop instrument (0.032 ng/mL). This work also: (1) identified potential adaptations (e.g., optimization of the plasmonically enhanced response for measurement by the handheld unit through a change in the excitation wavelength) to tighten the gap in performance; and (2) briefly examined the next steps and potential processes required to move this immunoassay platform closer to PON utility.

摘要

用于检测疾病生物标志物的技术是保护人类健康的关键组成部分。虽然过去几十年的工作已经重新定义了疾病生物标志物的低水平测量,但这些能力从正式临床环境到即时(PON)使用的转化要有限得多。本文介绍了旨在检查手持式拉曼光谱仪作为基于表面增强拉曼散射(SERS)的夹心免疫测定的 PON 电子读取器的潜在用途的实验结果。为此,本研究使用了最近开发的用于检测磷酸肌醇封端脂阿拉伯甘露聚糖(PILAM)的 SERS 检测程序,作为比较实验室级和手持式仪器性能的一种手段,从而评估手持式仪器用于 PON 部署的实用性。磷酸肌醇封端脂阿拉伯甘露聚糖是甘露糖封端脂阿拉伯甘露聚糖(ManLAM)的非致病性模拟物,甘露糖封端脂阿拉伯甘露聚糖是感染结核分枝杆菌(TB)个体血清和其他体液中发现的一种抗原标志物。然后将现场便携式光谱仪的测量结果与使用更灵敏的台式拉曼光谱仪获得的相同样品的结果进行比较。尽管两台光谱仪的操作设置不同(例如,信号积分时间),但结果很有希望,因为使用手持式系统检测到人血清中添加的 PILAM 的检测限(0.18ng/mL)接近台式仪器的检测限(0.032ng/mL)。这项工作还:(1)确定了潜在的适应方法(例如,通过改变激发波长来优化手持式仪器的等离子增强响应,以缩小性能差距);(2)简要检查了将该免疫测定平台更接近 PON 实用性所需的下一步和潜在过程。

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