Aslan Mete, Seymour Elif, Brickner Howard, Clark Alex E, Celebi Iris, Townsend Michael B, Satheshkumar Panayampalli S, Riley Megan, Carlin Aaron F, Ünlü M Selim, Ray Partha
Department of Electrical and Computer Engineering, Boston University, Boston, MA, 02215, USA.
iRiS Kinetics, Boston University, Business Incubation Center, Boston, MA, 02215, USA.
medRxiv. 2024 Jul 5:2024.07.03.24309903. doi: 10.1101/2024.07.03.24309903.
Diagnostic approaches that combine the high sensitivity and specificity of laboratory-based digital detection with the ease of use and affordability of point-of-care (POC) technologies could revolutionize disease diagnostics. This is especially true in infectious disease diagnostics, where rapid and accurate pathogen detection is critical to curbing the spread of disease. We have pioneered an innovative label-free digital detection platform that utilizes Interferometric Reflectance Imaging Sensor (IRIS) technology. IRIS leverages light interference from an optically transparent thin film, eliminating the need for complex optical resonances to enhance the signal by harnessing light interference and the power of signal averaging in shot-noise-limited operation to achieve virtually unlimited sensitivity. In our latest work, we have further improved our previous 'Single-Particle' IRIS (SP-IRIS) technology by allowing the construction of the optical signature of target nanoparticles (whole virus) from a single image. This new platform, 'Pixel-Diversity' IRIS (PD-IRIS), eliminated the need for z-scan acquisition, required in SP-IRIS, a time-consuming and expensive process, and made our technology more applicable to POC settings. Using PD-IRIS, we quantitatively detected the Monkeypox virus (MPXV), the etiological agent for Monkeypox (Mpox) infection. MPXV was captured by anti-A29 monoclonal antibody (mAb 69-126-3) on Protein G spots on the sensor chips and were detected at a limit-of-detection (LOD) - of 200 PFU/ml (~3.3 attomolar). PD-IRIS was superior to the laboratory-based ELISA (LOD - 1800 PFU/mL) used as a comparator. The specificity of PD-IRIS in MPXV detection was demonstrated using Herpes simplex virus, type 1 (HSV-1), and Cowpox virus (CPXV). This work establishes the effectiveness of PD-IRIS and opens possibilities for its advancement in clinical diagnostics of Mpox at POC. Moreover, PD-IRIS is a modular technology that can be adapted for the multiplex detection of pathogens for which high-affinity ligands are available that can bind their surface antigens to capture them on the sensor surface.
将基于实验室的数字检测的高灵敏度和特异性与即时检测（POC）技术的易用性和可承受性相结合的诊断方法，可能会彻底改变疾病诊断。在传染病诊断中尤其如此，因为快速准确的病原体检测对于遏制疾病传播至关重要。我们开创了一种创新的无标记数字检测平台，该平台利用干涉反射成像传感器（IRIS）技术。IRIS利用来自光学透明薄膜的光干涉，通过利用光干涉和散粒噪声限制操作中的信号平均能力来增强信号，从而无需复杂的光学共振即可实现几乎无限的灵敏度。在我们的最新工作中，我们通过允许从单个图像构建目标纳米颗粒（全病毒）的光学特征，进一步改进了我们之前的“单颗粒”IRIS（SP-IRIS）技术。这个新平台“像素多样性”IRIS（PD-IRIS），消除了SP-IRIS中所需的z扫描采集，这是一个耗时且昂贵的过程，并使我们的技术更适用于POC设置。使用PD-IRIS，我们定量检测了猴痘病毒（MPXV），这是猴痘（Mpox）感染的病原体。MPXV被传感器芯片上蛋白G斑点上的抗A29单克隆抗体（mAb 69-126-3）捕获，并在检测限（LOD）为200 PFU/ml（~3.3阿托摩尔）时被检测到。PD-IRIS优于用作对照的基于实验室的ELISA（LOD - 1800 PFU/mL）。使用1型单纯疱疹病毒（HSV-1）和牛痘病毒（CPXV）证明了PD-IRIS在MPXV检测中的特异性。这项工作确立了PD-IRIS的有效性，并为其在POC的Mpox临床诊断中的进一步发展开辟了可能性。此外，PD-IRIS是一种模块化技术，可以适用于对有高亲和力配体可用以结合其表面抗原以在传感器表面捕获它们的病原体进行多重检测。
