Department of Electrical Engineering, Kwangwoon University, 447-1 Wolgye, Nowon, Seoul, 01897, South Korea.
Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, Seoul, 02447, South Korea.
Sci Rep. 2017 Oct 30;7(1):14303. doi: 10.1038/s41598-017-14338-4.
Sensitivity and limit of detection (LOD) enhancement are essential criteria for the development of ultrasensitive molecular sensors. Although various sensor types have been investigated to enhance sensitivity and LOD, analyte detection and its quantification are still challenging, particularly for protein-protein interactions with low association constants. To solve this problem, here, we used ion concentration polarization (ICP)-based preconcentration to increase the local concentration of analytes in a microfluidic platform for LOD improvement. This was the first demonstration of a microfluidic device with an integrated ICP preconcentrator and interdigitated microelectrode (IME) sensor to detect small changes in surface binding between antigens and antibodies. We detected the amyloid beta (Aβ) protein, an Alzheimer's disease marker, with low binding affinity to its antibodies by adopting ICP preconcentration phenomena. We demonstrated that a combination of ICP preconcentrator and IME sensor increased the LOD by 13.8-fold to femtomolar level (8.15 fM), which corresponds to a significant advance for clinical applications.
灵敏度和检测限 (LOD) 的提升是开发超灵敏分子传感器的重要标准。尽管已经研究了各种传感器类型来提高灵敏度和 LOD，但分析物的检测及其定量仍然具有挑战性，特别是对于具有低缔合常数的蛋白质-蛋白质相互作用。为了解决这个问题，我们在这里使用基于离子浓度极化 (ICP) 的预浓缩来增加微流控平台中分析物的局部浓度，以提高 LOD。这是首次展示具有集成 ICP 预浓缩器和叉指微电极 (IME) 传感器的微流控设备，用于检测抗原和抗体之间表面结合的微小变化。我们通过采用 ICP 预浓缩现象来检测具有低结合亲和力的阿尔茨海默病标志物淀粉样蛋白 β (Aβ) 蛋白。我们证明，ICP 预浓缩器和 IME 传感器的组合将 LOD 提高了 13.8 倍，达到飞摩尔水平 (8.15 fM)，这对应于临床应用的重大进展。
