I-Corps: Nanophosphors as Ultra-Sensitive Lateral Flow Reporters in a Lab-on-Phone Platform

诊断的不确定性或延误会对发病率和死亡率造成重大影响，特别是在传染病方面。对于几种严重的医疗状况，可靠的诊断测试目前的周转时间为数小时至数天，此外还需要昂贵的设备和训练有素的人员。护理点（POC）诊断通过分散和快速的结果实现更好的疾病管理和患者护理，并且正在迅速增长。在所有现有的和潜在的POC技术和格式中，侧向流测试（LFT）是一种近三十年的技术，最容易满足可用性标准，因此，当它适用并具有足够的灵敏度时，它比其他格式更受欢迎。然而，用于几种危重疾病的市售LFT缺乏产生巨大临床影响所需的分析灵敏度和具有成本效益的定量能力。当分析物的特异性和稳定性抗体与由正确组分组成的LFT试纸组合使用时，LFT的分析灵敏度由报告颗粒的可检测性决定。 到目前为止，为了克服比色标记的局限性而开发的LFT报告物在POC市场上没有产生很大的影响，并且由于成本和实用性的结合，它们的采用可能仍然有限。所提出的技术中的关键创新是使用“纳米磷光体”，二氧化硅封装的持久发光纳米颗粒，作为侧向流动测试（LFT）报告物。纳米荧光粉可以通过LFT实现对复杂样品中分析物水平的客观、超灵敏和定量测量，LFT仅使用手机的内置光学器件和廉价的塑料附件进行读取。LFT由于其多功能性和简单性而成为最广泛使用的床旁检测形式之一。LFT在包括家庭妊娠测试在内的应用中取得了巨大的成功，但不是定量的，并且受到灵敏度和再现性的限制。纳米荧光粉具有强烈的发光发射，在暴露于从廉价的光学元件（如手机闪光灯）获得的光之后持续几分钟。因此，它们比目前使用的和视觉读取的胶体金更可检测，并且当用作LFT报告基因时，允许定量检测低得多的分析物浓度。

Diagnostic uncertainty or delay can exact a substantial toll on morbidity and mortality, especially with infectious diseases. For several critical medical conditions, reliable diagnostic tests currently have turnaround times of hours to days, besides requiring expensive equipment and trained personnel. Point-of-care (POC) diagnostics enable better disease management and patient care through decentralization and rapid time-to-result, and are rapidly growing in usage. Of all the existing and potential POC technologies and formats, the Lateral Flow Test (LFT), a nearly three decades-old technology, most readily meets the usability criteria and is, therefore, preferred over other formats when it is applicable and has sufficient sensitivity. However, commercially available LFTs for several critical diseases lack the analytical sensitivity and the cost-effective quantitative ability required to make a large clinical impact. When specific and stable antibodies to an analyte are used in combination with an LFT strip composed of the right components, the analytical sensitivity of an LFT is determined by the detectability of the reporter particle. The LFT reporters that have been developed thus far, to overcome the limitations of the colorimetric labels have not had a large impact in the POC market, and are likely to remain limited in their adoption, due to a combination of cost and practicality.The key innovation in the proposed technology is the use of 'nanophosphors', silica-encapsulated persistent luminescent nanoparticles, as Lateral Flow Test (LFT) reporters. Nanophosphors can enable the objective, ultrasensitive and quantitative measurement of analyte levels from complex samples through LFTs that use only a cell phone's built-in optics and an inexpensive plastic attachment for readout. The LFT is one of the most widely used point-of-care assay formats owing to its versatility and simplicity. LFTs have been hugely successful in applications including home pregnancy testing, but are not quantitative, and suffer from sensitivity and reproducibility limitations. Nanophosphors have an intense luminescence emission that lasts for several minutes after exposure to light available from inexpensive optical components like a cell phone flash. They are therefore more detectable than the currently used and visually-read colloidal gold, and when used as LFT reporters, allow the quantitative detection of much lower analyte concentrations.