Magnetic particles can enrich desired cell populations to aid in understanding cell-type functions and mechanisms, diagnosis, and therapy. As cells are heterogeneous in ligand type, location, expression, and density, careful consideration of magnetic particle design for positive isolation is necessary. Antigen-specific immune cells have low frequencies, which has made studying, identifying, and utilizing these cells for therapy a challenge. Here we demonstrate the importance of magnetic particle design based on the biology of T cells. We create magnetic particles which recognize rare antigen-specific T cells and quantitatively investigate important particle properties including size, concentration, ligand density, and ligand choice in enriching these rare cells. We observe competing optima among particle parameters, with 300 nm particles functionalized with a high density of antigen-specific ligand achieving the highest enrichment and recovery of target cells. In enriching and then activating an endogenous response, 300 nm aAPCs generate nearly 65% antigen-specific T cells with at least 450-fold expansion from endogenous precursors and a 5-fold increase in numbers of antigen-specific cells after only seven days. This systematic study of particle properties in magnetic enrichment provides a case study for the engineering design principles of particles for the isolation of rare cells through biological ligands.

磁性粒子可以丰富所需的细胞群，以帮助了解细胞类型的功能和机制、诊断和治疗。由于细胞在配体类型、位置、表达和密度方面是异质的，因此有必要仔细考虑用于阳性分离的磁粉设计。抗原特异性免疫细胞的频率较低，这使得研究、识别和利用这些细胞进行治疗成为一项挑战。在这里，我们展示了基于 T 细胞生物学的磁性粒子设计的重要性。我们创造了能够识别稀有抗原特异性 T 细胞的磁性粒子，并定量研究重要的粒子特性，包括大小、浓度、配体密度和配体选择，以丰富这些稀有细胞。我们观察到粒子参数之间的竞争最优，用高密度抗原特异性配体功能化的 300 nm 颗粒实现靶细胞的最高富集和回收率。在富集然后激活内源性反应时，300 nm aAPC 产生近 65% 的抗原特异性 T 细胞，仅 7 天后，内源性前体细胞扩增至少 450 倍，抗原特异性细胞数量增加 5 倍。这项对磁富集中粒子特性的系统研究为通过生物配体分离稀有细胞的粒子的工程设计原理提供了一个案例研究。300 nm aAPC 产生近 65% 的抗原特异性 T 细胞，仅 7 天后，内源性前体细胞扩增至少 450 倍，抗原特异性细胞数量增加 5 倍。这项对磁富集中粒子特性的系统研究为通过生物配体分离稀有细胞的粒子的工程设计原理提供了一个案例研究。300 nm aAPC 产生近 65% 的抗原特异性 T 细胞，仅 7 天后，内源性前体细胞扩增至少 450 倍，抗原特异性细胞数量增加 5 倍。这项对磁富集中粒子特性的系统研究为通过生物配体分离稀有细胞的粒子的工程设计原理提供了一个案例研究。