Neairat Tajweed, Al-Gawati Mahmoud, Tul Ain Qura, Assaifan Abdulaziz K, Alshamsan Aws, Alarifi Abdulaziz, Alodhayb Abdullah N, Alzahrani Khalid E, Albrithen Hamad
Department of Physics and Astronomy, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
Biological and Environmental Sensing Research Unit, King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, Saudi Arabia.
Saudi Pharm J. 2024 Jun;32(6):102051. doi: 10.1016/j.jsps.2024.102051. Epub 2024 Mar 27.
The ongoing global concern of cancer worldwide necessitates the development of advanced diagnostic and therapeutic strategies. The majority of recent detection strategies involve the employment of biomarkers. A critical biomarker for cancer immunotherapy efficacy and patient prognosis is Programmed Death Ligand 1 (PD-L1), which is a key immune checkpoint protein. PD-L1 can be particularly linked to cancer progression and therapy response. Current detection methods, such as enzyme-linked immunosorbent assay (ELISA), face limitations like high cost, time consumption, and complexity. This study introduces a microcantilever-based biosensor designed for the detection of soluble PD-L1 (sPD-L1), which has a specific association with PD-L1. The biosensor utilizes anti-PD-L1 as the sensing layer, capitalizing on the specific binding affinity between anti-PD-L1 and sPD-L1. The presence of the sensing layer was confirmed through Atomic Force Microscopy (AFM) and contact angle measurements. Binding between sPD-L1 and anti-PD-L1 induces a shift in the microcantilever's resonance frequency, which is proportional to the PD-L1 concentration. Notably, the resonance frequency shift demonstrates a robust linear relationship with the increasing biomarker concentration, ranging from 0.05 ng/ml to 500 ng/ml. The detection limit of the biosensor was determined to be approximately 10 pg/ml. The biosensor demonstrates excellent performance in detecting PD-L1 with high specificity even in complex biological matrices. This innovative approach not only provides a promising tool for early cancer diagnosis but also holds potential for monitoring immunotherapy efficacy, paving the way for personalized and effective cancer treatments.
全球范围内对癌症的持续关注使得先进的诊断和治疗策略的开发成为必要。最近的大多数检测策略都涉及生物标志物的应用。癌症免疫治疗疗效和患者预后的一个关键生物标志物是程序性死亡配体1(PD-L1),它是一种关键的免疫检查点蛋白。PD-L1与癌症进展和治疗反应密切相关。当前的检测方法,如酶联免疫吸附测定(ELISA),面临着成本高、耗时和复杂等局限性。本研究介绍了一种基于微悬臂梁的生物传感器,用于检测与PD-L1具有特异性关联的可溶性PD-L1(sPD-L1)。该生物传感器利用抗PD-L1作为传感层,利用抗PD-L1与sPD-L1之间的特异性结合亲和力。通过原子力显微镜(AFM)和接触角测量证实了传感层的存在。sPD-L1与抗PD-L1之间的结合会导致微悬臂梁共振频率的偏移,该偏移与PD-L1浓度成正比。值得注意的是,共振频率偏移与生物标志物浓度增加呈现出稳健的线性关系,范围从0.05 ng/ml到500 ng/ml。该生物传感器的检测限确定为约10 pg/ml。该生物传感器即使在复杂的生物基质中也能以高特异性检测PD-L1,表现出优异的性能。这种创新方法不仅为早期癌症诊断提供了一种有前景的工具,而且在监测免疫治疗疗效方面也具有潜力,为个性化和有效的癌症治疗铺平了道路。