Nanotechnology platform for cell-based magnetic assays

描述(由申请人提供)： MagneSensors的计划旨在开发一种纳米技术平台，使用超灵敏的磁性传感器和磁性标签对活细胞进行强大的新细胞分析。该磁检测平台使用高温(高温)超导量子干涉器件(SQUID)来检测标记有磁性纳米颗粒的生物分子产生的磁场。第一阶段的工作专门旨在利用创新的纳米技术来减少和控制磁性传感器和磁性纳米颗粒标签的关键尺寸，以驱动下一代仪器，然后展示其在敏感细胞分析中的适用性。第一阶段使用模型系统进行概念验证细胞分析。细胞检测的特异性目标包括：1)检测100个贴壁活细胞(HUVEC)上的细胞表面受体(ICAM-1)，2)检测10个非贴壁活细胞(CRL-1923)上的细胞表面受体(Ig)，以及3)检测10,000个“正常”T细胞背景中的50个“罕见”B细胞。为了改进磁性传感器，需要更小(10-20 nm)的有源器件，以及更小(30-80 nm)、更均匀、更强大的磁性纳米颗粒，以进一步推动仪器的灵敏度朝着雄心勃勃的第二阶段目标--单细胞检测和稀有细胞检测--迈进。新细胞分析的好处包括：a)灵敏地检测“正常”细胞群中的稀有细胞(如母体血液中的胎儿细胞、转移的肿瘤细胞、受感染的宿主细胞)；b)对细胞表面受体或蛋白质进行超灵敏的“混合测量”分析，能够在血液的手指上进行，无需样品制备。后者最终可能取代细胞培养，用于感染(如败血症和感染性休克)的快速检测，在这些情况下，需要立即回答，而拖延可能被证明是致命的。这一“纳米生物技术”计划将受益于一群经验丰富的物理学家、化学家和生物学家的密切跨学科合作。

DESCRIPTION (provided by applicant): MagneSensors' program is aimed at developing a nanotechnology platform that uses ultra-sensitive magnetic sensors and magnetic labels to perform powerful new cell assays on live cells. This magnetic detection platform uses high temperature (high-Tc) superconducting quantum interference devices (SQUIDs) to detect the magnetic field generated by biomolecules tagged with magnetic nanoparticles. The Phase I effort is specifically aimed at employing innovative nanotechnology to reduce and control critical dimensions in magnetic sensors and magnetic nanoparticle labels to drive next generation instrumentation and then demonstrating applicability in sensitive cell assays. Phase I uses model systems for proof-of-concept cell assays. Cell assay specific aims include: 1) detection of cell surface receptors (ICAM-1) on 100 adherent live cells (HUVEC), 2) detection of cell surface receptors (Ig) on 10 non-adherent live cells (CRL-1923), and 3) detection of 50 "rare" B cells in a background of 10,000 "normal" T cells. Smaller (10-20 nm) active devices to improve the magnetic sensors, and small (30-80 nm), more uniform, and more powerful magnetic nanoparticles are required to further push the instrument sensitivity towards the ambitious Phase II goals of single cell detection and rare cell detection. The benefits of the new cell assays include: a) the sensitive detection of rare cells within a "normal" cell population (such as fetal cells in maternal blood, metastatic tumor cells, infected host cells), b) ultra-sensitive "mix and measure" assays on cell surface receptors or proteins capable of being performed on a finger stick of blood and no sample preparation. The latter could eventually replace cell culturing for the rapid detection of infections (e.g. sepsis and septic shock) where an immediate answer is needed and delay can prove fatal. This "nanobiotechnology" program will benefit from the close interdisciplinary collaboration of an experienced group of physicists, chemists, and biologists.