Chen Kuan-Yu, Tsai Yi-Cheng, Kuo Feng-Chih, Lee Mel S, Hu Chih-Chien, Lee Gwo-Bin
Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
Department of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Anal Chim Acta. 2025 Jan 22;1336:343493. doi: 10.1016/j.aca.2024.343493. Epub 2024 Nov 28.
Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes joint damage and progressive destruction of adjacent cartilage and bones. Quick and accurate detection of rheumatoid factors (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP) in serum is effective in diagnosing RA and preventing its progression. However, current methods for detecting these two biomarkers are costly, time-consuming, labor-intensive, and require specialized equipment. To address these limitations, a new microfluidic chip was developed to automatically conduct the dual-RA biomarker detection assay.
The integrated chip, which was equipped with micropumps, microvalves, and micromixers, was positioned underneath an optical detection module composed of a light-emitting diode, optical filters, condenser lenses, and a silicon photomultiplier to quantify the fluorescence signals of magnetic bead-bound analytes in two separate micro-chambers. The dual-target assay required only 5 μL of serum and took only 100 min to complete, accurately measuring RF and anti-CCP at concentrations ranging from 0.8 to 106.0 IU/mL and 6.0-59.0 U/mL, respectively. Compared with the gold standard, the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the developed on-chip assays were 95.5 %, 94.4 %, 100.0 %, 100.0 %, 80.0 % for both RF and anti-CCP detection with 30 clinical samples.
With its compact size of only 350 mm × 238 mm x 153 mm and low volumes of samples/reagents required, this system shows promise for point-of-care testing. The compact size, low sample volume requirement, and high performance of the developed system could significantly improve RA management and patient outcomes by providing rapid and accurate diagnostics in clinical settings.
类风湿性关节炎（RA）是一种慢性自身免疫性疾病，可导致关节损伤以及相邻软骨和骨骼的渐进性破坏。快速准确地检测血清中的类风湿因子（RF）和抗环瓜氨酸肽抗体（抗CCP）对于诊断RA和预防其进展有效。然而，目前检测这两种生物标志物的方法成本高、耗时、劳动强度大，且需要专门设备。为解决这些局限性，开发了一种新型微流控芯片以自动进行双RA生物标志物检测分析。
集成芯片配备有微泵、微阀和微混合器，位于由发光二极管、光学滤光片、聚光透镜和硅光电倍增管组成的光学检测模块下方，以量化两个独立微腔中磁珠结合分析物的荧光信号。双靶点分析仅需5μL血清，仅需100分钟即可完成，分别准确测量浓度范围为0.8至106.0 IU/mL和6.0 - 59.0 U/mL的RF和抗CCP。与金标准相比，对于30份临床样本的RF和抗CCP检测，所开发的芯片检测方法的准确性、敏感性、特异性、阳性预测值和阴性预测值均为95.5%、94.4%、100.0%、100.0%、80.0%。
该系统尺寸紧凑，仅为350 mm×238 mm x 153 mm，所需样本/试剂体积小，有望用于即时检测。所开发系统的紧凑尺寸、低样本量要求和高性能可通过在临床环境中提供快速准确的诊断，显著改善RA的管理和患者预后。
