Department of Chemistry, Oregon State University, 153 Gilbert Hall, Corvallis, OR, 97331, USA.
Materials Science Program, College of Engineering, Oregon State University, Corvallis, OR, 97331, USA.
Anal Bioanal Chem. 2021 Jul;413(17):4511-4520. doi: 10.1007/s00216-021-03420-6. Epub 2021 May 27.
Separation of blood plasma or serum from blood is essential for accurate analysis. Conventional blood separation requires instrumentation, reagents, and large sample volumes, limiting this process to laboratory environments with trained personnel. Full implementation of effective blood separation and analysis on microliter sample volumes for point of care (POC) diagnostics has proven extremely challenging resulting in a growing market demand, with common challenges such as expensive device fabrication processes or devices being comprised of materials which are not easily disposable. We developed a membrane-based wicking microfluidic device which is made using a simple fabrication process. This device uses a unique 3D flow channel geometry, fabricated in a polycaprolactone-filled glass microfiber membrane, to efficiently separate microliter sample volumes of blood. Colorimetric assay chemistries were integrated to demonstrate utility of these devices in POC diagnostics. The devices are capable of separating both fresh and anticoagulant-treated blood at microscale sample volumes (<15.0 μL). Modifications to the base device are also reported herein which increased sample volume capacity and separation efficiency. Integrated colorimetric assay enabled semi-quantitative detection of conjugated bilirubin in real blood samples (1.0-1.5 mg/dL). These blood separation devices, fabricated on polycaprolactone-filled glass microfiber, enabled effective blood plasma (anticoagulant-treated blood) and serum (fresh blood) separation with microscale sample volumes. Sample volume capacity and separation efficiency are customizable for specific applications and devices can be integrated with downstream assay chemistries to develop complete POC devices that offer blood separation and diagnostics at the same time on a single membrane.
从血液中分离血浆或血清对于准确分析至关重要。传统的血液分离需要仪器、试剂和大量样本，这使得该过程仅限于配备有训练有素的人员的实验室环境。为了在即时护理（POC）诊断中实现对微升样本量的有效血液分离和分析，已经证明这是一项极具挑战性的任务，这导致市场需求不断增长，常见的挑战包括设备制造工艺昂贵或设备由不易处理的材料制成。我们开发了一种基于膜的吸液微流控装置，该装置采用简单的制造工艺制成。该装置使用独特的 3D 流道几何形状，在聚己内酯填充的玻璃微纤维膜中制造，可有效分离微升样本量的血液。集成了比色分析化学方法，以证明这些设备在 POC 诊断中的实用性。这些设备能够在微尺度样本量（<15.0 μL）下分离新鲜和抗凝处理的血液。本文还报道了对基础设备的改进，这些改进提高了样品容量和分离效率。集成的比色分析能够对半定量检测实际血液样本中的结合胆红素（1.0-1.5 mg/dL）。这些基于聚己内酯填充的玻璃微纤维的血液分离装置能够有效分离微升样本量的抗凝处理的血浆（血液）和新鲜的血清。可根据特定应用定制样品容量和分离效率，并且可以将设备与下游分析化学方法集成，在单个膜上同时提供血液分离和诊断功能，从而开发完整的 POC 设备。
