Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Lab Chip. 2017 Nov 7;17(22):3772-3784. doi: 10.1039/c7lc00722a.
The regulation effect of surface charges on the transport of electrons in nanomaterials and ions in nanofluidic devices has been widely used to develop highly sensitive and label-free electrical biosensors. The intrinsic limitation to the clinical application of surface charge-effect nano-electrical biosensors is that they usually do not function in physiological conditions normally with high ionic concentrations (∼160 mM), in which the surface charges are screened within a short distance (<1 nm at 160 mM). In this work, we developed a general strategy that enables surface charge-effect electrical biomolecular detection in physiological conditions with an integrated mechanism for enhancement of the limit of detection (LOD) by in situ preconcentration of target molecules during incubation and creation of a transient low ionic concentration environment during the signal read-out step using reconfigurable ion concentration polarization (ICP). We demonstrated the effectiveness of this strategy in a simple nanofluidic biosensor named a nanofluidic crystal (NFC), which can be prepared within hours and without expensive equipment. Our results indicate that the ion depletion effect of ICP could lower the ionic concentration by at least 200 fold and provide a stable ionic environment for over 15 s, enabling electrical detection of proteins and DNAs in serum and urine with LODs of 1-10 nM. We further reconfigured the device to preconcentrate target biomolecules before detection using the enrichment effect of ICP, obtaining LODs of 10-100 pM for proteins and DNAs in physiological conditions. By overcoming the inherent constraint on buffer conditions and the issues regarding fabrication, we believe that this work represents significant progress towards the practical application of surface charge-effect nano-electrical biosensors in point-of-care diagnostics and clinical medicine.
表面电荷对纳米材料中电子输运和纳米流体器件中离子输运的调节作用已被广泛用于开发高灵敏度和无标记的电生物传感器。表面电荷效应纳米电子生物传感器在临床应用中的固有局限性在于，它们通常不适用于生理条件下高离子浓度（约 160mM），在生理条件下，表面电荷在短距离内（160mM 时小于 1nm）被屏蔽。在这项工作中，我们开发了一种通用策略，使表面电荷效应电生物分子检测在生理条件下具有增强检测限（LOD）的集成机制，即在孵育过程中通过目标分子的原位预浓缩，以及在信号读出步骤中使用可重构离子浓度极化（ICP）创建瞬态低离子浓度环境。我们在一种简单的纳米流体生物传感器，即纳米流体晶体（NFC）中证明了这种策略的有效性，该传感器可以在数小时内制备，无需昂贵的设备。我们的结果表明，ICP 的离子耗尽效应可将离子浓度降低至少 200 倍，并为超过 15s 提供稳定的离子环境，从而能够在血清和尿液中以 1-10nM 的 LOD 进行蛋白质和 DNA 的电检测。我们进一步重新配置了该设备，在检测前使用 ICP 的浓缩效应来浓缩目标生物分子，从而在生理条件下获得蛋白质和 DNA 的 10-100pM 的 LOD。通过克服缓冲条件的固有约束和制造问题，我们相信这项工作代表了表面电荷效应纳米电子生物传感器在即时诊断和临床医学中的实际应用方面的重大进展。
