Institute for Collaborative Biotechnologies, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Sci Transl Med. 2013 Nov 27;5(213):213ra165. doi: 10.1126/scitranslmed.3007095.
A sensor capable of continuously measuring specific molecules in the bloodstream in vivo would give clinicians a valuable window into patients' health and their response to therapeutics. Such technology would enable truly personalized medicine, wherein therapeutic agents could be tailored with optimal doses for each patient to maximize efficacy and minimize side effects. Unfortunately, continuous, real-time measurement is currently only possible for a handful of targets, such as glucose, lactose, and oxygen, and the few existing platforms for continuous measurement are not generalizable for the monitoring of other analytes, such as small-molecule therapeutics. In response, we have developed a real-time biosensor capable of continuously tracking a wide range of circulating drugs in living subjects. Our microfluidic electrochemical detector for in vivo continuous monitoring (MEDIC) requires no exogenous reagents, operates at room temperature, and can be reconfigured to measure different target molecules by exchanging probes in a modular manner. To demonstrate the system's versatility, we measured therapeutic in vivo concentrations of doxorubicin (a chemotherapeutic) and kanamycin (an antibiotic) in live rats and in human whole blood for several hours with high sensitivity and specificity at subminute temporal resolution. We show that MEDIC can also obtain pharmacokinetic parameters for individual animals in real time. Accordingly, just as continuous glucose monitoring technology is currently revolutionizing diabetes care, we believe that MEDIC could be a powerful enabler for personalized medicine by ensuring delivery of optimal drug doses for individual patients based on direct detection of physiological parameters.
一种能够在体内持续测量血液中特定分子的传感器将为临床医生提供一个了解患者健康状况及其对治疗反应的有价值窗口。这种技术将实现真正的个性化医疗，治疗剂可以根据每个患者的最佳剂量进行定制，以最大限度地提高疗效并最小化副作用。不幸的是，目前只有少数目标（如葡萄糖、乳糖和氧气）能够进行连续实时测量，而少数现有的连续测量平台也不能用于监测其他分析物，如小分子治疗剂。有鉴于此，我们开发了一种能够实时跟踪活体动物中广泛循环药物的实时生物传感器。我们用于体内连续监测的微流控电化学探测器 (MEDIC) 不需要外源性试剂，在室温下运行，并且可以通过以模块化方式交换探针来重新配置以测量不同的目标分子。为了展示系统的多功能性，我们以高灵敏度和特异性在亚分钟的时间分辨率下测量了活老鼠和人全血中的阿霉素（一种化疗药物）和卡那霉素（一种抗生素）的治疗体内浓度数小时。我们表明 MEDIC 还可以实时获得单个动物的药代动力学参数。因此，正如连续血糖监测技术目前正在彻底改变糖尿病护理一样，我们相信 MEDIC 可以通过直接检测生理参数来确保为每个患者提供最佳药物剂量，从而成为个性化医疗的有力推动者。
