Deptartment of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040, China.
Deptartment of Physics, Fudan University, Shanghai, 200040, China.
Sci Rep. 2017 Aug 17;7(1):8596. doi: 10.1038/s41598-017-08674-8.
The ability to simultaneously detect JAK2 V617F and MPL W515K/L mutations would substantially improve the early diagnosis of myeloproliferative neoplasms (MPNs) and decrease the risk of arterial thrombosis. The goal of this study is to achieve a point of care testing platform for simultaneous analysis of major genetic alterations in MPN. Here, we report a microfluidic platform including a glass capillary containing polypropylene matrix that extracts genomic DNA from a drop of whole blood, a microchip for simultaneous multi-gene mutation screening, and a handheld battery-powered heating device. The µmLchip system was successfully used for point-of-care identification of the JAK2 V617F and MPL W515K/L mutations. The µmLchip assays were then validated by mutation analysis with samples from 100 MPN patients who had previously been analyzed via unlabeled probe melting curve analysis or real-time PCR. The results from the µmLchip were in perfect agreement with those from the other methods, except for one discrepant result that was negative in the unlabeled probe melting curve analysis but positive in the µmLchip. After T-A cloning, sequences of cloned PCR products revealed JAK2 V617F mutation in the sample. The portable microfluidic platform may be very attractive in developing point-of-care diagnostics for MPL W515K/L and JAK2 V617F mutations.
同时检测 JAK2 V617F 和 MPL W515K/L 突变的能力将极大地提高骨髓增殖性肿瘤(MPN)的早期诊断率,并降低动脉血栓形成的风险。本研究的目的是开发一种即时检测平台,用于同时分析 MPN 中的主要遗传改变。在这里,我们报告了一个微流控平台,包括一个含有聚丙烯基质的玻璃毛细管,该毛细管可从一滴全血中提取基因组 DNA,一个用于同时进行多基因突变筛选的微芯片,以及一个手持式电池供电的加热装置。µmLchip 系统成功地用于即时识别 JAK2 V617F 和 MPL W515K/L 突变。然后,通过对 100 名 MPN 患者的样本进行突变分析来验证 µmLchip 检测,这些患者之前已经通过非标记探针熔解曲线分析或实时 PCR 进行了分析。µmLchip 的结果与其他方法完全一致,除了一个不一致的结果,即在非标记探针熔解曲线分析中为阴性,但在 µmLchip 中为阳性。在 T-A 克隆后,克隆 PCR 产物的序列显示该样本存在 JAK2 V617F 突变。这种便携式微流控平台在开发 MPL W515K/L 和 JAK2 V617F 突变的即时检测诊断方面可能非常有吸引力。