International Iberian Nanotechnology Laboratory (INL), Avda. Mestre José Veiga, 4715-310 Braga, Portugal.
Life and Health Sciences Research Institute (ICVS), Escola de Medicina, Universidade do Minho, Campus Gualtar, 4710-057 Braga, Portugal.
Analyst. 2024 May 13;149(10):2812-2825. doi: 10.1039/d4an00158c.
Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and associated with poor prognosis. Unfortunately, most of the patients that achieve clinical complete remission after the treatment will ultimately relapse due to the persistence of minimal residual disease (MRD), that is not measurable using conventional technologies in the clinic. Microfluidics is a potential tool to improve the diagnosis by providing early detection of MRD. Herein, different designs of microfluidic devices were developed to promote lateral and vertical mixing of cells in microchannels to increase the contact area of the cells of interest with the inner surface of the device. Possible interactions between the cells and the surface were studied using fluid simulations. For the isolation of leukemic blasts, a positive selection strategy was used, targeting the cells of interest using a panel of specific biomarkers expressed in immature and aberrant blasts. Finally, once the optimisation was complete, the best conditions were used to process patient samples for downstream analysis and benchmarking, including phenotypic and genetic characterisation. The potential of these microfluidic devices to isolate and detect AML blasts may be exploited for the monitoring of AML patients at different stages of the disease.
急性髓细胞白血病（AML）是成人中最常见的急性白血病形式，预后不良。不幸的是，大多数在治疗后达到临床完全缓解的患者最终会因微小残留病（MRD）的持续存在而复发，而 MRD 在临床上使用常规技术是无法检测到的。微流控技术是一种通过提供对 MRD 的早期检测来改善诊断的潜在工具。本文中，开发了不同设计的微流控装置以促进细胞在微通道中的横向和纵向混合，从而增加与装置内表面接触的目标细胞的接触面积。使用流体模拟研究了细胞与表面之间的可能相互作用。为了分离白血病母细胞，使用了正向选择策略，使用在不成熟和异常母细胞中表达的特定生物标志物组合来靶向目标细胞。最后，一旦优化完成，就使用最佳条件处理患者样本进行下游分析和基准测试，包括表型和遗传特征。这些微流控装置分离和检测 AML 母细胞的潜力可用于监测疾病不同阶段的 AML 患者。
