Gong Yan, Hu Jie, Choi Jane Ru, You Minli, Zheng Yamin, Xu Bo, Wen Ting, Xu Feng
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi'an Jiaotong University.
Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University.
Int J Nanomedicine. 2017 Jun 15;12:4455-4466. doi: 10.2147/IJN.S135735. eCollection 2017.
Heart failure (HF) has become a major cause of morbidity and mortality with a significant global economic burden. Although well-established clinical tests could provide early diagnosis, access to these tests is limited in developing countries, where a relatively higher incidence of HF is present. This has prompted an urgent need for developing a cost-effective, rapid and robust diagnostic tool for point-of-care (POC) detection of HF. Lateral flow immunoassay (LFIA) has found widespread applications in POC diagnostics. However, the low sensitivity of LFIA limits its ability to detect important HF biomarkers (e.g., brain natriuretic peptide [BNP]) that are normally present in low concentration in blood. To address this issue, we developed an improved LFIA by optimizing the gold nanoparticle (GNP)-antibody conjugate conditions (e.g., the conjugate pH and the amount of added antibody), the diameter of GNP and the concentration of antibody embedded on the test line and modifying the structure of test strip. Through these improvements, the proposed test strip enabled the detection of BNP down to 0.1 ng/mL within 10-15 min, presenting ~15-fold sensitivity enhancement over conventional lateral flow assay. We also successfully applied our LFIA in the analysis of BNP in human serum samples, highlighting its potential use for clinical assessment of HF. The developed LFIA for BNP could rapidly rule out HF with the naked eye, offering tremendous potential for POC test and personalized medicine.
心力衰竭(HF)已成为发病和死亡的主要原因,带来了巨大的全球经济负担。尽管成熟的临床试验能够提供早期诊断,但在HF发病率相对较高的发展中国家,这些检测手段的可及性有限。这促使人们迫切需要开发一种经济高效、快速且可靠的诊断工具,用于即时检测(POC)HF。侧向流动免疫分析(LFIA)在POC诊断中得到了广泛应用。然而,LFIA的低灵敏度限制了其检测血液中通常以低浓度存在的重要HF生物标志物(如脑钠肽[BNP])的能力。为了解决这一问题,我们通过优化金纳米颗粒(GNP)-抗体偶联条件(如偶联物pH值和添加抗体的量)、GNP直径以及包被在检测线上的抗体浓度,并对试纸条结构进行修饰,开发了一种改进的LFIA。通过这些改进,所提出的试纸条能够在10 - 15分钟内检测低至0.1 ng/mL的BNP,与传统侧向流动分析相比,灵敏度提高了约15倍。我们还成功地将我们的LFIA应用于人体血清样本中BNP的分析,突出了其在HF临床评估中的潜在用途。所开发的用于BNP的LFIA能够用肉眼快速排除HF,为POC检测和个性化医疗提供了巨大潜力。