Tunable Detection Sensitivity of Opiates in Urine via a Label-Free Porous Silicon Competitive Inhibition Immunosensor
Tunable Detection Sensitivity of Opiates in Urine via a Label-Free Porous Silicon Competitive Inhibition Immunosensor
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DOI：
10.1021/ac902453h
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发表时间：
2010-01-15
影响因子：
7.4
通讯作者：
DeLouise, Lisa A.
中科院分区：
文献类型：
--
作者：
Bonanno, Lisa M.;DeLouise, Lisa A.
目前，需要基于实验室的高通量和可靠的即时药物筛选方法。我们在此展示了一种基于芯片的无标记多孔硅 (PSi) 光子传感器，用于检测尿液中的阿片类药物。该技术为传统标记药物筛选免疫测定提供了一种经济高效的替代方案，并具有转化为多重分析的潜力。揭示了表面化学和竞争性结合测定方案对阿片检测灵敏度的重要影响。通过改变所应用的尿液样本体积（100-5μL），可以将灵敏度和检测范围调整大约3个数量级（18.0nM至10.8μM），从而导致竞争性结合响应曲线的系统性变化。尿液（15μL）中吗啡的检测范围（0.36-4.02μM）被设计为跨越目前医用阿片类尿液筛查中的阳性截止值（1.05μM吗啡）。除了其他常见阿片类药物、吗啡、吗啡-3-葡萄糖醛酸苷、6-乙酰吗啡之外，与羟考酮具有理想的高交叉反应性，这表明比目前的商业筛选测定具有优势，同时保持了对可卡因代谢物的低干扰。这项研究独特地展示了 PSi 传感器技术作为一种廉价、快速且可靠的药物筛选技术。此外，所开发的多功能表面化学可以在一系列固体支持的传感器上实施，以进行竞争性抑制测定。
Currently, there is need for laboratory-based high-throughput and reliable point-of-care drug screening methodologies. We demonstrate here a chip-based label-free porous silicon (PSi) photonic sensor for detecting opiates in urine. This technique provides a cost-effective alternative to conventional labeled drug screening immunoassays with potential for translation to multiplexed analysis. Important effects of surface chemistry and competitive binding assay protocol on the sensitivity of opiate detection are revealed. Capability to tune sensitivity and detection range over similar to 3 orders of magnitude (18.0 nM to 10.8 mu M) was achieved by varying the applied urine specimen volume (100-5 mu L), which results in systematic shifts in the competitive binding response curve. A detection range (0.36-4.02 mu M) of morphine in urine (15 mu L) was designed to span the current positive cutoff value (1.05 mu M morphine) in medical opiate urine screening. Desirable high cross-reactivity to oxycodone, in addition to other common opiates, morphine, morphine-3-glucuronide, 6-acetyl morphine, demonstrates an advantage over current commercial screening assays, while low interference with cocaine metabolite was maintained. This study uniquely displays PSi sensor technology as an inexpensive, rapid, and reliable drug screening technology. Furthermore, the versatile surface chemistry developed can be implemented on a range of solid-supported sensors to conduct competitive inhibition assays.