Prokhorov General Physics Institute of the Russian Academy of Sciences, 38 Vavilov St, 119991, Moscow, Russia; Moscow Institute of Physics and Technology (National Research University), 9 Institutskii per., Dolgoprudny, Moscow Region, 141700, Russia.
Prokhorov General Physics Institute of the Russian Academy of Sciences, 38 Vavilov St, 119991, Moscow, Russia; Moscow Institute of Physics and Technology (National Research University), 9 Institutskii per., Dolgoprudny, Moscow Region, 141700, Russia.
Biosens Bioelectron. 2020 Jul 1;159:112187. doi: 10.1016/j.bios.2020.112187. Epub 2020 Apr 11.
A multiplex label-free biosensor is developed for diagnostics of autoimmune diseases by highly sensitive measuring in human serum both critical characteristics of autoantibody: concentration and native kinetic parameters that reflect autoantibody aggressiveness to the organism's tissues. The biosensor is based on the spectral-correlation interferometry and image processing of a microarray glass biochip, affordable to be single-used in medical applications. Simultaneous 25-min detection and activity characterization of several autoantibodies in the same serum sample have been demonstrated for anti-thyroglobulin (anti-TG) and anti-thyroid peroxidase (anti-TPO) as models. The biosensor offers extremely high sensitivity: limits of detection in serum are 1.7 IU/mL and 6 IU/mL for anti-TPO and anti-TG, respectively. The dynamic range covers the whole range of clinically relevant concentrations of the autoantibodies up to 1000 IU/mL. The developed method of characterization of autoantibody activity by recording the kinetics of their binding with free native antigens is based on autoantibody polyvalency. The measurements in clinical serum samples have shown that the native kinetic parameters are independent of concentration. The proposed biosensor and method of native kinetic registration can be used to develop new criteria for comprehensive diagnostics of autoimmune diseases, based not only on traditional measurements of concentration but also on quantitative evaluation of autoantibody aggressiveness. The developed method can be adapted to other label-free sensors such as those based on the surface plasmon resonance, optical waveguides, etc.
一种多重无标记生物传感器被开发出来，用于通过在人类血清中进行高灵敏度测量来诊断自身免疫性疾病，同时测量自身抗体的两个关键特征：浓度和反映自身抗体对机体组织侵袭性的天然动力学参数。该生物传感器基于光谱相关干涉测量法和微阵列玻璃生物芯片的图像处理，价格实惠，可在医疗应用中一次性使用。以抗甲状腺球蛋白（anti-TG）和抗甲状腺过氧化物酶（anti-TPO）为例，已经证明了在同一样本血清中同时检测和分析几种自身抗体的 25 分钟检测和活性特征。该生物传感器具有极高的灵敏度：在血清中的检测限分别为 anti-TPO 和 anti-TG 的 1.7 IU/mL 和 6 IU/mL。动态范围涵盖了自身抗体的整个临床相关浓度范围，高达 1000 IU/mL。通过记录其与游离天然抗原结合的动力学来表征自身抗体活性的方法是基于自身抗体的多价性。在临床血清样本中的测量表明，天然动力学参数与浓度无关。所提出的生物传感器和天然动力学记录方法可用于开发新的自身免疫性疾病综合诊断标准，不仅基于传统的浓度测量，还基于对自身抗体侵袭性的定量评估。该方法可以适应其他无标记传感器，如基于表面等离子体共振、光波导等的传感器。
