Kumar Ashok A, Patton Matthew R, Hennek Jonathan W, Lee Si Yi Ryan, D'Alesio-Spina Gaetana, Yang Xiaoxi, Kanter Julie, Shevkoplyas Sergey S, Brugnara Carlo, Whitesides George M
School of Engineering and Applied Sciences.
Department of Chemistry and Chemical Biology, and.
Proc Natl Acad Sci U S A. 2014 Oct 14;111(41):14864-9. doi: 10.1073/pnas.1414739111. Epub 2014 Sep 2.
Although effective low-cost interventions exist, child mortality attributable to sickle cell disease (SCD) remains high in low-resource areas due, in large part, to the lack of accessible diagnostic methods. The presence of dense (ρ > 1.120 g/cm(3)) cells is characteristic of SCD. The fluid, self-assembling step-gradients in density created by aqueous multiphase systems (AMPSs) identifies SCD by detecting dense cells. AMPSs separate different forms of red blood cells by density in a microhematocrit centrifuge and provide a visual means to distinguish individuals with SCD from those with normal hemoglobin or with nondisease, sickle-cell trait in under 12 min. Visual evaluation of a simple two-phase system identified the two main subclasses of SCD [homozygous (Hb SS) and heterozygous (Hb SC)] with a sensitivity of 90% (73-98%) and a specificity of 97% (86-100%). A three-phase system identified these two types of SCD with a sensitivity of 91% (78-98%) and a specificity of 88% (74-98%). This system could also distinguish between Hb SS and Hb SC. To the authors' knowledge, this test demonstrates the first separation of cells by density with AMPSs, and the usefulness of AMPSs in point-of-care diagnostic hematology.
尽管存在有效的低成本干预措施,但在资源匮乏地区,镰状细胞病(SCD)导致的儿童死亡率仍然很高,这在很大程度上是由于缺乏可及的诊断方法。存在致密细胞(ρ > 1.120 g/cm³)是SCD的特征。由水相多相系统(AMPSs)产生的流体、自组装密度梯度通过检测致密细胞来识别SCD。AMPSs在微量血细胞比容离心机中按密度分离不同形式的红细胞,并提供一种视觉手段,可在12分钟内将SCD患者与正常血红蛋白或非疾病性镰状细胞性状患者区分开来。对一个简单的两相系统进行视觉评估,识别出SCD的两个主要亚类[纯合子(Hb SS)和杂合子(Hb SC)],灵敏度为90%(73 - 98%),特异性为97%(86 - 100%)。一个三相系统识别这两种类型SCD的灵敏度为91%(78 - 98%),特异性为88%(74 - 98%)。该系统还可以区分Hb SS和Hb SC。据作者所知,这项测试展示了首次利用AMPSs按密度分离细胞,以及AMPSs在即时诊断血液学中的实用性。