Time-of-flight (TOF) magnetic sensing of rolling immunomagnetically-labeled cells offers great potential for single cell function analysis at the bedside in even optically opaque media, such as whole blood. However, due to the spatial resolution of the sensor and the low flow rate regime required to observe the behavior of rolling cells, the concentration range of such a workflow is limited. Potential clinical applications, such as testing of leukocyte function, require a cytometer which can cover a cell concentration range of several orders of magnitude. This is a challenging task for an integrated dilution-free workflow, as for high cell concentrations coincidences need to be avoided, while for low cell concentrations sufficient statistics should be provided in a reasonable time-to-result. Here, we extend the spatial bandwidth of a magnetoresistive sensor with an adaptive and integratable workflow concept combining mechanical and magnetophoretic guiding of magnetically labeled targets for in-situ enrichment over a dynamic concentration range of 3 orders of magnitude. We achieve hybrid integration of the enrichment strategy in a cartridge mold and a giant-magnetoresistance (GMR) sensor in a functionalized Quad Flat No-Lead (QFN) package, which allows for miniaturization of the Si footprint for potential low-cost bedside testing. The enrichment results demonstrate that TOF magnetic flow cytometry with adaptive particle focusing can match the clinical requirements for a point-of-care (POC) cytometer and can potentially be of interest for other sheath-less methodologies requiring workflow integration.

滚动免疫磁标记细胞的飞行时间（TOF）磁感测甚至可以在不透光的介质（例如全血）中在床边进行单细胞功能分析，具有巨大的潜力。但是，由于传感器的空间分辨率和观察滚动池行为所需的低流速状态，这种工作流程的集中范围受到限制。潜在的临床应用（例如白细胞功能测试）要求使用流式细胞仪，该细胞仪可以覆盖几个数量级的细胞浓度范围。对于集成的无稀释工作流程而言，这是一项艰巨的任务，因为对于高细胞浓度，需要避免巧合，而对于低细胞浓度，则应在合理的时间内提供足够的统计数据。这里，我们通过自适应和可集成的工作流程概念扩展了磁阻传感器的空间带宽，该工作流程概念结合了磁性标记目标的机械和磁致导航，可在3个数量级的动态浓度范围内进行原位富集。我们实现了盒式模具中的富集策略与功能化四方扁平无铅（QFN）封装中的巨磁阻（GMR）传感器的混合集成，从而可以将Si的占位面积最小化，以进行潜在的低成本床边测试。富集结果表明，具有自适应粒子聚焦功能的TOF磁流式细胞术可以满足即时医疗（POC）细胞仪的临床需求，并且可能对于需要工作流程集成的其他无鞘方法很有兴趣。