Department of Chemical Engineering, Loughborough University, Loughborough, Leicestershire LE11 3TU, UK.
Department of Chemical Engineering, Loughborough University, Loughborough, Leicestershire LE11 3TU, UK and Department of Chemical Engineering, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
Analyst. 2017 Mar 13;142(6):858-882. doi: 10.1039/c6an02445a.
The latest clinical procedures for the timely and cost-effective diagnosis of chronic and acute clinical conditions, such as cardiovascular diseases, cancer, chronic respiratory diseases, diabetes or sepsis (i.e. the biggest causes of death worldwide), involve the quantitation of specific protein biomarkers released into the blood stream or other physiological fluids (e.g. urine or saliva). The clinical thresholds are usually in the femtomolar to picolomar range, and consequently the measurement of these protein biomarkers heavily relies on highly sophisticated, bulky and automated equipment in centralised pathology laboratories. The first microfluidic devices capable of measuring protein biomarkers in miniaturised immunoassays were presented nearly two decades ago and promised to revolutionise point-of-care (POC) testing by offering unmatched sensitivity and automation in a compact POC format; however, the development and adoption of microfluidic protein biomarker tests has fallen behind expectations. This review presents a detailed critical overview into the pipeline of microfluidic devices developed in the period 2005-2016 capable of measuring protein biomarkers from the pM to fM range in formats compatible with POC testing, with a particular focus on the use of affordable microfluidic materials and compact low-cost signal interrogation. The integration of these two important features (essential unique selling points for the successful microfluidic diagnostic products) has been missed in previous review articles and explain the poor adoption of microfluidic technologies in this field. Most current miniaturised devices compromise either on the affordability, compactness and/or performance of the test, making current tests unsuitable for the POC measurement of protein biomarkers. Seven core technical areas, including (i) the selected strategy for antibody immobilisation, (ii) the surface area and surface-area-to-volume ratio, (iii) surface passivation, (iv) the biological matrix interference, (v) fluid control, (vi) the signal detection modes and (vii) the affordability of the manufacturing process and detection system, were identified as the key to the effective development of a sensitive and affordable microfluidic protein biomarker POC test.
最新的临床程序可用于及时且经济有效地诊断慢性和急性临床病症，例如心血管疾病、癌症、慢性呼吸道疾病、糖尿病或败血症（即全球最大的死亡原因），涉及到定量分析释放到血流或其他生理液（例如尿液或唾液）中的特定蛋白质生物标志物。临床阈值通常在飞摩尔到皮摩尔范围内，因此这些蛋白质生物标志物的测量严重依赖于中央病理学实验室中高度复杂、庞大且自动化的设备。近二十年前，第一批能够在微型免疫分析中测量蛋白质生物标志物的微流控设备面世，它们承诺通过在紧凑的 POCT 格式中提供无与伦比的灵敏度和自动化来彻底改变 POCT 测试；然而，微流控蛋白质生物标志物测试的开发和采用并未达到预期。本文详细介绍了 2005-2016 年期间开发的微流控设备的流水线，这些设备能够以与 POCT 测试兼容的格式测量 pM 到 fM 范围内的蛋白质生物标志物，特别关注使用经济实惠的微流控材料和紧凑的低成本信号检测。这两个重要特征（成功的微流控诊断产品的独特卖点）的集成在之前的综述文章中被忽略了，这解释了微流控技术在该领域采用率低的原因。目前的大多数小型化设备要么在测试的可负担性、紧凑性和/或性能方面做出妥协，要么使当前的测试不适合蛋白质生物标志物的 POCT 测量。七个核心技术领域，包括（i）抗体固定化的选择策略、（ii）表面积和表面积-体积比、（iii）表面钝化、（iv）生物基质干扰、（v）流体控制、（vi）信号检测模式以及（vii）制造过程和检测系统的负担能力，被确定为开发敏感且经济实惠的微流控蛋白质生物标志物 POCT 测试的关键。
