Raman spectroscopy-based sensitive and specific detection of glycated hemoglobin.
Raman spectroscopy-based sensitive and specific detection of glycated hemoglobin.
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DOI：
10.1021/ac203266a
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发表时间：
2012-03-06
影响因子：
7.4
通讯作者：
Feld, Michael S.
中科院分区：
文献类型：
--
作者：
Barman, Ishan;Dingari, Narahara Chari;Kang, Jeon Woong;Horowitz, Gary L.;Dasari, Ramachandra R.;Feld, Michael S.
近年来，糖化血红蛋白（HbA 1c）已越来越多地被接受为糖尿病患者治疗中平均血糖的功能指标。重要的是，HbA 1c提供了总血糖暴露的替代指标，因为它代表了全天（包括餐后）的血糖。在本文中，我们提出并证明了拉曼光谱法作为一种新型分析方法定量检测HbA 1c的潜力，无需使用外部染料或试剂。使用滴涂沉积拉曼（DCDR）技术，我们观察到血红蛋白分子的非酶促糖基化（糖化）导致所获得的光谱中的细微但可辨别且高度可重复的变化，这使得能够使用标准化学计量学方法准确测定糖化和非糖化血红蛋白。所获得的拉曼光谱显示出在液滴中不同位置处的光谱特性的优异再现性，并且显示出光谱强度对分析物浓度的线性依赖性。此外，在溶血产物模型中，开发的HbA 1c多变量校准模型显示出高度的预测准确性和精密度-检测限几乎是临床实践中遇到的最低生理浓度的15倍。在这项概念验证研究中实现的出色准确性和再现性为表征和定量广泛用于生物制药开发的（治疗性）蛋白质的糖基化状态开辟了实质性途径。我们还设想，所提出的方法可以提供一个强大的工具，用于高通量HbA 1c传感多组分混合物，并可能在溶血和全血裂解物样品。
In recent years, glycated hemoglobin (HbA1c) has been increasingly accepted as a functional metric of mean blood glucose in the treatment of diabetic patients. Importantly, HbA1c provides an alternate measure of total glycemic exposure due to the representation of blood glucose throughout the day, including post-prandially. In this article, we propose and demonstrate the potential of Raman spectroscopy as a novel analytical method for quantitative detection of HbA1c, without using external dyes or reagents. Using the drop coating deposition Raman (DCDR) technique, we observe that the non-enzymatic glycosylation (glycation) of the hemoglobin molecule results in subtle but discernible and highly reproducible changes in the acquired spectra, which enable the accurate determination of glycated and non-glycated hemoglobin using standard chemometric methods. The acquired Raman spectra display excellent reproducibility of spectral characteristics at different locations in the drop and show a linear dependence of the spectral intensity on the analyte concentration. Furthermore, in hemolysate models, the developed multivariate calibration models for HbA1c show a high degree of prediction accuracy and precision - with a limit of detection that is nearly a factor of 15 smaller than the lowest physiological concentrations encountered in clinical practice. The excellent accuracy and reproducibility achieved in this proof-of-concept study opens substantive avenues for characterization and quantification of the glycosylation status of (therapeutic) proteins, which are widely used for biopharmaceutical development. We also envision that the proposed approach can provide a powerful tool for high-throughput HbA1c sensing in multi-component mixtures and potentially in hemolysate and whole blood lysate samples.
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