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可能会对发病率和死亡率造成重大损失，特别是在传染病方面。对于几种危重的医疗条件，可靠的诊断测试目前需要数小时到数天的周转时间，此外还需要昂贵的设备和训练有素的人员。医疗点(POC)诊断通过分散化和快速结果时间实现更好的疾病管理和患者护理，并且使用量正在迅速增长。在所有现有和潜在的POC技术和格式中，侧向流动测试(LFT)是一项已有近30年历史的技术，最容易满足可用性标准，因此在适用和具有足够灵敏度的情况下，它比其他格式更受欢迎。然而，商业上可获得的几种危重疾病的LFT缺乏分析灵敏度和成本效益高的量化能力，无法产生巨大的临床影响。当针对分析物的特定和稳定的抗体与由正确成分组成的LFT试条结合使用时，LFT的分析灵敏度取决于报告颗粒的可检测性。到目前为止，为克服比色标签的局限性而开发的LFT记录器在POC市场上没有产生太大影响，由于成本和实用性的结合，它们的采用可能仍然受到限制。所提出技术的关键创新是使用纳米荧光粉，即二氧化硅封装的永久发光纳米颗粒，作为侧向流动测试(LFT)记录器。纳米磷光体可以通过LFT客观、超灵敏和定量地测量复杂样品中的分析物水平，这种LFT只使用手机的内置光学元件和廉价的塑料附件进行读出。由于其通用性和简单性，LFT是使用最广泛的护理点检测格式之一。LFT在包括家庭怀孕测试在内的应用中取得了巨大的成功，但它不是定量的，而且受到灵敏度和重复性的限制。纳米荧光粉在接触到廉价光学元件(如手机闪光灯)提供的光线后，会发出强烈的发光，持续几分钟。因此，它们比目前使用的和目视读取的胶体金更容易检测，当用作LFT报告时，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.