Department of Materials Science and Engineering, The Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv University, Tel Aviv 69978, Israel.
School of Chemistry, Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
ACS Nano. 2024 Nov 5;18(44):30848-30862. doi: 10.1021/acsnano.4c11612. Epub 2024 Oct 28.
Biomarkers detection has become essential in medical diagnostics and early detection of life-threatening diseases. Modern-day medicine relies heavily on painful and invasive tests, with the extraction of large volumes of venous blood being the most common tool of biomarker detection. These tests are time-consuming, complex, expensive and require multiple sample manipulations and trained staff. The application of "intradermal" biosensors utilizing microneedles as minimally invasive sensing elements for capillary blood biomarkers detection has gained extensive interest in the past few years as a central point-of-care (POC) detection platform. Herein, we present a diagnosis paradigm based on vertically aligned nanopillar array-embedded microneedles sampling-and-detection elements for the direct optical detection and quantification of biomarkers in capillary blood. We present here a demonstration of the simple fabrication route for the creation of a multidetection-zone silicon nanopillar array, embedded in microneedle elements, followed by their area-selective chemical modification, toward the multiplex intradermal biomarkers detection. The utilization of the rapid and specific antibody-antigen binding, combined with the intrinsically large sensing area created by the nanopillar array, enables the simultaneous efficient ultrafast and highly sensitive intradermal capillary blood sampling and detection of protein biomarkers of clinical relevance, without requiring the extraction of blood samples for the biomarkers analysis. Through preliminary and experiments, the direct intradermal in-skin blood extraction-free platform has demonstrated excellent sensitivity (low pM) and specificity for the accurate multiplex detection of protein biomarkers in capillary blood.
生物标志物检测在医学诊断和危及生命疾病的早期检测中变得至关重要。现代医学严重依赖痛苦和有创的测试，其中提取大量静脉血是生物标志物检测最常用的工具。这些测试既耗时又复杂，费用高昂，需要多次样本操作和经过培训的人员。在过去的几年中，利用微针作为微创传感元件的“皮内”生物传感器在毛细血管血液生物标志物检测中的应用引起了广泛关注，成为了一个重要的即时护理（POC）检测平台。在这里，我们提出了一种基于垂直排列纳米柱阵列嵌入式微针采样和检测元件的诊断范例，用于直接光学检测和定量毛细血管血液中的生物标志物。我们展示了一种简单的制造方法，用于创建嵌入微针元件的多检测区硅纳米柱阵列，然后对其进行选择性化学修饰，以实现多通道皮内生物标志物检测。利用快速且特异性的抗体-抗原结合，结合纳米柱阵列本身所创造的大固有传感面积，能够同时高效地进行超快速和高灵敏度的皮内毛细血管血液采样和检测，而无需提取血液样本进行生物标志物分析。通过初步实验，该免提取皮内血液的直接皮内平台已经证明了其在准确检测毛细血管血液中蛋白质生物标志物方面的出色灵敏度（低皮摩尔）和特异性。
