Stein Erich W, Singh Saurabh, McShane Michael J
Biomedical Engineering Program and Institute for Micromanufacturing, Louisiana Tech University, Ruston, Louisiana 71272, USA.
Anal Chem. 2008 Mar 1;80(5):1408-17. doi: 10.1021/ac701738e. Epub 2008 Feb 1.
Microscale implantable fluorescent sensors that can be transdermally interrogated using light are being pursued as a minimally invasive biochemical monitoring technology for in vivo applications. Previously, we reported the development of an enzymatic-based sensing platform characterized using glucose as a model biochemical analyte for minimally invasive diabetic monitoring. In this work, surface-adsorbed polyelectrolyte nanofilms were employed to modulate the relative fluxes of glucose and oxygen into the sensor, allowing response characteristics, namely, analytical range and sensitivity, to be tuned. Modulation of substrate transport properties were obtained by varying surface-adsorbed nanofilm thicknesses, ionic strength of assembly conditions, and outermost constituents. In general, increasing film thickness through additional cycles of adsorption resulted in consistently decreased glucose flux, correspondingly decreasing sensitivity and increasing range. While the two components of the nanofilms remained the same [poly(allylamine hydrochloride), PAH; poly(sodium 4-styrenesulfonate)}, the assembly conditions and terminal layer were found to strongly influence sensor behavior. Specifically, without added salt in assembly conditions, glucose diffusion was significantly decreased when films were capped with PAH, resulting in reduced sensitivity and extended range of response. With added salt, however, sensor response was the same for films of the same thickness but different terminal materials. These findings demonstrate that sensor response may be customized to cover the hypo- (0-80 mg/dL), normo- (80-120 mg/dL), and hyperglycemic levels (>120 mg/dL) from a single batch of particles through appropriate selection of coating structure and assembly conditions. Furthermore, the results indicate nanofilms of only 12-nm thickness could significantly affect response behavior, confirming predicted behavior by models of sensor reaction-diffusion kinetics. These findings demonstrate the ability to engineer sensor response properties using a simple, cost-effective means and lay the groundwork for developing additional highly sensitive biochemical monitors.
可通过光进行经皮询问的微型植入式荧光传感器正作为一种用于体内应用的微创生化监测技术而被研究。此前，我们报道了一种基于酶的传感平台的开发，该平台以葡萄糖作为微创糖尿病监测的模型生化分析物进行表征。在这项工作中，使用表面吸附的聚电解质纳米膜来调节葡萄糖和氧气进入传感器的相对通量，从而能够调整响应特性，即分析范围和灵敏度。通过改变表面吸附纳米膜的厚度、组装条件的离子强度和最外层成分来实现对底物传输特性的调节。一般来说，通过额外的吸附循环增加膜厚度会导致葡萄糖通量持续下降，相应地降低灵敏度并扩大范围。虽然纳米膜的两种成分保持不变[聚（烯丙胺盐酸盐），PAH；聚（4-苯乙烯磺酸钠）]，但发现组装条件和终端层对传感器行为有强烈影响。具体而言，在组装条件下不添加盐时，当膜用PAH封端时，葡萄糖扩散显著降低，导致灵敏度降低和响应范围扩大。然而，添加盐后，相同厚度但不同终端材料的膜的传感器响应相同。这些发现表明，通过适当选择涂层结构和组装条件，可以定制传感器响应以覆盖来自同一批颗粒的低血糖（0-80mg/dL）、正常血糖（80-120mg/dL）和高血糖水平（>120mg/dL）。此外，结果表明仅12纳米厚的纳米膜就能显著影响响应行为，证实了传感器反应扩散动力学模型预测的行为。这些发现证明了使用简单、经济高效的方法设计传感器响应特性的能力，并为开发更多高灵敏度生化监测器奠定了基础。
