Development and validation of an optical biosensor for rapid monitoring of adalimumab in serum of patients with Crohn's disease
Development and validation of an optical biosensor for rapid monitoring of adalimumab in serum of patients with Crohn's disease
复制标题
DOI：
10.1002/dta.2250
复制
发表时间：
2018-03-01
影响因子：
2.9
通讯作者：
Gils, Ann
中科院分区：
文献类型：
--
作者：
Bian, Sumin;Lu, Jiadi;Gils, Ann
阿达利单抗的治疗药物监测建议用于改善克罗恩病患者的治疗结果。进行酶联免疫吸附试验需要相当长的时间才能得出结果，而且有必要收集多个样本，以降低每次测定阿达利单抗的成本。在这项研究中，我们旨在开发和验证一种适用于使用基于光纤表面等离子体共振(FO-SPR)的传感器来测量单个阿达利单抗血清样本的快速检测方法。因此，我们将MA-ADM28B8作为捕获抗体固定在FO-探针上，并结合MA-ADM40D8作为金纳米颗粒的检测抗体。在1/400稀释血清中，阿达利单抗的量效曲线范围为2.5~40 ng/m L。阿达利玛单抗浓度在1到16g/mL之间的患者的血清样本被检测，而阴性对照的样本中添加16g/mL的英夫利昔单抗，没有明显的信号。使用预功能化的FO探头，该技术测量单个样品只需不到45分钟。生物传感器与酶联免疫吸附试验的测量结果显示，皮尔逊相关系数为0.99，类内系数为0.99，具有很好的一致性。与酶联免疫吸附试验相比，缩短的检测时间和测量单个样本的可能性是主要的优势。开发和验证的光学adalimumab生物传感器可以作为克罗恩病患者adalimumab定量的有价值的护理点诊断工具。
Therapeutic drug monitoring of adalimumab is recommended to improve therapeutic outcome in patients with Crohn's disease. Performing an ELISA requires a rather long time-to-result and the necessity of collecting multiple samples to decrease the cost per adalimumab determination. In this study, we aim to develop and validate a rapid assay suitable for measuring a single adalimumab serum sample using a fiber-optic surface plasmon resonance (FO-SPR) based sensor. Therefore, we have immobilized MA-ADM28B8 as capture antibody on an FO-probe and conjugated MA-ADM40D8 as detecting antibody to gold nanoparticles. A dose-response curve ranging from 2.5 to 40ng/mL adalimumab was obtained in 1/400 diluted serum. Serum samples of patients with adalimumab concentrations between 1 and 16g/mL were measured whereas the negative control, a sample spiked with infliximab at a concentration of 16g/mL, showed no significant signal. Using a pre-functionalized FO-probe, the technology requires less than 45minutes for measuring a single sample. Comparison of measurements between the biosensor and the ELISA revealed an excellent agreement with a Pearson r coefficient of 0.99 and an intra-class coefficient of 0.99. The reduced assay time and the possibility of measuring a single sample are major advantages compared to the ELISA. The developed and validated optical adalimumab biosensor could be a valuable point-of-care diagnostic tool for adalimumab quantification in patients with Crohn's disease.