Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America ; Department of Laboratory Medicine, Boston Children's Hospital, Boston, Massachusetts, United States of America.
PLoS One. 2013 Sep 30;8(9):e75616. doi: 10.1371/journal.pone.0075616. eCollection 2013.
Monitoring for drug-induced liver injury (DILI) via serial transaminase measurements in patients on potentially hepatotoxic medications (e.g., for HIV and tuberculosis) is routine in resource-rich nations, but often unavailable in resource-limited settings. Towards enabling universal access to affordable point-of-care (POC) screening for DILI, we have performed the first field evaluation of a paper-based, microfluidic fingerstick test for rapid, semi-quantitative, visual measurement of blood alanine aminotransferase (ALT). Our objectives were to assess operational feasibility, inter-operator variability, lot variability, device failure rate, and accuracy, to inform device modification for further field testing. The paper-based ALT test was performed at POC on fingerstick samples from 600 outpatients receiving HIV treatment in Vietnam. Results, read independently by two clinic nurses, were compared with gold-standard automated (Roche Cobas) results from venipuncture samples obtained in parallel. Two device lots were used sequentially. We demonstrated high inter-operator agreement, with 96.3% (95% C.I., 94.3-97.7%) agreement in placing visual results into clinically-defined "bins" (<3x, 3-5x, and >5x upper limit of normal), >90% agreement in validity determination, and intraclass correlation coefficient of 0.89 (95% C.I., 0.87-0.91). Lot variability was observed in % invalids due to hemolysis (21.1% for Lot 1, 1.6% for Lot 2) and correlated with lots of incorporated plasma separation membranes. Invalid rates <1% were observed for all other device controls. Overall bin placement accuracy for the two readers was 84% (84.3%/83.6%). Our findings of extremely high inter-operator agreement for visual reading-obtained in a target clinical environment, as performed by local practitioners-indicate that the device operation and reading process is feasible and reproducible. Bin placement accuracy and lot-to-lot variability data identified specific targets for device optimization and material quality control. This is the first field study performed with a patterned paper-based microfluidic device and opens the door to development of similar assays for other important analytes.
在资源丰富的国家，对可能导致肝损伤的药物（例如用于治疗艾滋病毒和结核病的药物）进行定期监测，通过连续测量转氨酶来监测药物性肝损伤（DILI），这是常规做法，但在资源有限的环境中通常无法进行。为了实现普遍获得负担得起的即时护理（POC）DILI 筛查，我们首次对基于纸张的微流控指尖测试进行了现场评估，用于快速、半定量、可视化测量血液丙氨酸氨基转移酶（ALT）。我们的目标是评估操作可行性、操作员间变异性、批间变异性、设备故障率和准确性，为进一步的现场测试提供设备改进信息。在越南，600 名接受艾滋病毒治疗的门诊患者进行了现场指尖采血，使用基于纸张的 ALT 测试在 POC 进行。由两名诊所护士独立读取结果，并与同时从静脉穿刺样本获得的金标准自动化（罗氏 Cobas）结果进行比较。连续使用了两个设备批次。我们证明了高度的操作员间一致性，将视觉结果放入临床定义的“箱”（<3x、3-5x 和>5x 正常值上限）中的一致性为 96.3%（95%置信区间，94.3-97.7%），有效性确定的一致性>90%，以及 0.89（95%置信区间，0.87-0.91）的组内相关系数。由于溶血，两个批次的无效率观察到不同（批次 1 为 21.1%，批次 2 为 1.6%），并且与所包含的血浆分离膜批次相关。所有其他设备对照的无效率均<1%。两位读者的整体箱放置准确性为 84%（84.3%/83.6%）。我们发现，在当地从业者执行的目标临床环境中，通过视觉读取获得的操作员间高度一致的结果表明，设备操作和读取过程是可行且可重复的。箱放置准确性和批间变异性数据为设备优化和材料质量控制确定了具体目标。这是第一个针对图案化纸张基微流控设备进行的现场研究，为开发其他重要分析物的类似分析方法开辟了道路。
