Abstract：
Lateral flow devices (LFDs) or lateral flow tests (LFTs) are one of the most widely used biosensor platforms for point-of-care (POC) diagnostics. The basic LFD design has remained largely unchanged since its first appearance, and this has limited LFD use in clinical applications due to a general lack of analytical sensitivity. We report here a comprehensive study of the use of laser-patterned geometric control barriers that influence the flow dynamics within an LFD, with the specific aim of enhancing LFD sensitivity and lowering the limit of detection (LOD). This control of sample flow produces an increase in the time available for optimizing the binding kinetics of the implemented assay. The geometric modification to the flow path is in the form of a constriction that is produced by depositing a photo-sensitive polymer onto the nitrocellulose membrane which when polymerized, creates impermeable barrier walls through the depth of the membrane. Both the position of the constriction within the flow path and the number of constrictions allow for an increase in the sensitivity because of a slower overall flow rate within the test and a larger volume of sample per unit width of the test line. For these high sensitivity LFDs (HS-LFD), through optimization of the constriction position and addition of a second constriction we attained a 62% increase in test line color intensity for the detection of procalcitonin (PCT) and were also able to lower the LOD from 10 ng/mL to 1 ng/mL. In addition, of relevance for future commercial exploitation, this also significantly decreases the antibody consumption per device leading to reduced costs for test production. We have further tested our HS-LFD with contrived human samples, validating its application for future clinical use.
摘要：
侧流装置(LFD)或侧流测试(LFT)是用于即时(POC)诊断的最广泛使用的生物传感器平台之一。基本的LFD设计自首次出现以来基本保持不变，这限制了LFD在临床应用中的使用，因为一般缺乏分析灵敏度。我们在这里报告了对影响LFD内流动动力学的激光图案化几何控制屏障的使用的全面研究。具体目的是提高LFD灵敏度和降低检测限(LOD)。样品流的这种控制导致可用于优化实施的测定的结合动力学的时间增加。对流动路径的几何修改是通过将光敏聚合物沉积到硝化纤维素膜上而产生的收缩形式，当聚合时，通过膜的深度创建不可渗透的屏障墙。由于测试内较慢的总流速和测试线的每单位宽度的较大体积的样品,所以流动路径内的收缩部的位置和收缩部的数量都允许灵敏度的增加。对于这些高灵敏度LFD（HS-LFD），通过优化收缩位置和添加第二个收缩，我们获得了用于检测降钙素原（PCT）的测试线颜色强度的62％增加，并且还能够将LOD从10ng/mL降低到1ng/mL。此外,与未来的商业开发有关，这也显著降低了每个设备的抗体消耗,从而降低了测试生产成本.我们用人为样本进一步测试了我们的HS-LFD，验证其未来临床应用。
