Białas Katarzyna, Tay Hui Min, Petchakup Chayakorn, Salimian Razieh, Ward Stephen G, Lindsay Mark A, Hou Han Wei, Estrela Pedro
Centre for Bioengineering & Biomedical Technologies (CBio), University of Bath, Calverton Down, Bath, BA2 7AY, United Kingdom.
Department of Electronic & Electrical Engineering, University of Bath, Claverton Down, Bath, BA2 7AY, United Kingdom.
Microsyst Nanoeng. 2025 Apr 9;11(1):63. doi: 10.1038/s41378-025-00893-8.
Since the onset of the HIV epidemic, assessing CD4 T-cells has become a routine procedure for evaluating immune deficiency, with flow cytometry established as the gold standard. Over time, various strategies and platforms have been introduced to improve CD4 cell enumeration, aiming to enhance the performance of diagnostic devices and bring the service closer to patients. These advancements are particularly critical for low-resource settings and point-of-care applications, where the excellent performance of flow cytometry is hindered by its unsuitability in such environments. This work presents an innovative electrochemical microfluidic device that, with further development, could be applied for HIV management in low resource settings. The setup integrates an electrochemical sensor within a PDMS microfluidic structure, allowing for on-chip electrode functionalization and cell detection. Using electrochemical impedance spectroscopy, the biosensor demonstrates a linear detection range from 1.25 × 10 to 2 × 10 cells/mL, with a detection limit of 1.41 × 10 cells/mL for CD4 cells isolated from blood samples, aligning with clinical ranges for both healthy and HIV patients. The biosensor shows specificity towards CD4 cells with negligible response to monocytes, neutrophils, and bovine serum albumin. Its integration with a microfluidic chip for sensor fabrication and cell detection, compact size, minimal manual handling, ease of fabrication, electrochemical detection capability, and potential for multiplexing together with the detection range make the device particularly advantageous for use in low-resource settings, standing out among other devices described in the literature. This study also investigates the integration of a microfluidic Dean Flow Fractionation (DFF) chip for cell separation.
自艾滋病毒流行以来,评估CD4 T细胞已成为评估免疫缺陷的常规程序,流式细胞术被确立为金标准。随着时间的推移,人们引入了各种策略和平台来改进CD4细胞计数,旨在提高诊断设备的性能并使服务更贴近患者。这些进展对于资源匮乏地区和即时检测应用尤为关键,在这些环境中,流式细胞术因其不适用性而无法发挥其卓越性能。这项工作展示了一种创新的电化学微流控装置,经过进一步开发,可应用于资源匮乏地区的艾滋病毒管理。该装置将电化学传感器集成在聚二甲基硅氧烷(PDMS)微流控结构中,实现芯片上电极功能化和细胞检测。利用电化学阻抗谱,该生物传感器对从血样中分离出的CD4细胞的线性检测范围为1.25×10至2×10个细胞/毫升,检测限为1.41×10个细胞/毫升,与健康人和艾滋病毒患者的临床范围相符。该生物传感器对CD4细胞具有特异性,对单核细胞、中性粒细胞和牛血清白蛋白的反应可忽略不计。它与用于传感器制造和细胞检测的微流控芯片集成、尺寸紧凑、人工操作最少、易于制造、具有电化学检测能力以及与检测范围相关的多重检测潜力,使得该装置在资源匮乏地区使用时特别具有优势,在文献中描述的其他装置中脱颖而出。本研究还探讨了用于细胞分离的微流控迪恩流分馏(DFF)芯片的集成。