MIP Diagnostics Ltd., Fielding Johnson Building, University of Leicester, LE1 7RH, UK.
Nanoscale. 2018 Jan 25;10(4):2081-2089. doi: 10.1039/c7nr07785h.
Molecularly Imprinted Polymers (MIPs) are synthetic receptors that are able to selectively bind their target molecule and, for this reason, they are currently employed as recognition elements in sensors. In this work, MIP nanoparticles (nanoMIPs) are produced by solid-phase synthesis for a range of templates with different sizes, including a small molecule (biotin), two peptides (one derived from the epithelial growth factor receptor and vancomycin) and a protein (trypsin). NanoMIPs are then dipcoated on the surface of thermocouples that measure the temperature inside a liquid flow cell. Binding of the template to the MIP layer on the sensitive area of the thermocouple tip blocks the heat-flow from the sensor to the liquid, thereby lowering the overall temperature measured by the thermocouple. This is subsequently correlated to the concentration of the template, enabling measurement of target molecules in the low nanomolar regime. The significant improvement in the limit of detection (a magnitude of three orders compared to previously used MIP microparticles) can be attributed to their high affinity, enhanced conductivity and increased surface-to-volume ratio. It is the first time that these nanosized recognition elements are used in combination with thermal detection, and it is the first report on MIP-based thermal sensors for determining protein levels. The developed thermal sensors have a high selectivity, fast measurement time (<5 min), and data analysis is straightforward, which makes it possible to monitor biomolecules in real-time. The set of biomolecules discussed in this manuscript show that it is possible to cover a range of template molecules regardless of their size, demonstrating the general applicability of the biosensor platform. In addition, with its high commercial potential and biocompatibility of the MIP receptor layer, this is an important step towards sensing assays for diagnostic applications that can be used in vivo.
分子印迹聚合物（MIPs）是能够选择性结合其目标分子的合成受体，因此，它们目前被用作传感器中的识别元件。在这项工作中，通过固相合成生产了一系列具有不同尺寸的模板的 MIP 纳米颗粒（nanoMIPs），包括小分子（生物素）、两种肽（一种来自表皮生长因子受体和万古霉素）和一种蛋白质（胰蛋白酶）。然后，将 nanoMIPs 浸涂在热电偶的表面上，热电偶测量液体流动池内的温度。模板与热电偶尖端敏感区域上的 MIP 层的结合阻止了热量从传感器流向液体，从而降低了热电偶测量的整体温度。这随后与模板的浓度相关联，从而能够在纳摩尔级低的范围内测量目标分子。检测限的显著提高（与之前使用的 MIP 微球相比提高了三个数量级）归因于它们的高亲和力、增强的导电性和增加的表面积与体积比。这是第一次将这些纳米级识别元件与热检测结合使用，也是首次报道基于 MIP 的用于测定蛋白质水平的热传感器。所开发的热传感器具有高选择性、快速测量时间（<5 分钟）和简单的数据分析，这使得能够实时监测生物分子。本文讨论的一组生物分子表明，无论其大小如何，都可以覆盖一系列模板分子，证明了生物传感器平台的通用性。此外，由于 MIP 受体层具有高商业潜力和生物相容性，这是朝着可用于体内的诊断应用的传感分析迈出的重要一步。
