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单分子免疫检测技术研究进展 被引量:3

Advances in Single Molecule Immunoassay
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摘要 早诊断、早发现、早治疗是提升肿瘤患者生存率的主要手段。临床常用的免疫学检测方法如酶联免疫吸附法、化学发光法等,其检测灵敏度多限制在10^(-14)~10^(-12)mol/L,无法满足早期诊断的需求。单分子免疫检测法,可将待检测分子限制在极小空间范围内(nL以下),对检测信号进行绝对计数,从而实现痕量(可达10^(-18)mol/L)标志物的检测。这一超高灵敏度技术实现的关键在于将检测范围限制在极小体积内。经过数十年发展,不论是物理隔离还是利用纳米孔,抑或通过改进显微镜性能,均可在极小体积内(10^(-21)L)对信号进行检测。目前基于微阵列的SimoA检测系统已成为单分子免疫检测的金标准,Quanterix公司基于此开发的HD-1分析仪已进入市场应用。基于微液滴的单分子免疫检测技术主要限于实验室,但具有床旁检测的优势。重点介绍了基于物理隔离形式如微阵列和微液滴的单分子免疫检测进展,为进一步开发超高灵敏度检测方法并促进未来临床应用提供理论基础。 Early diagnosis,early detection,and early treatment is an important strategy for improving the survival rate of patients.However,the current immunological reagents based on enzyme-linked immunosorbent assay and chemiluminescence are mostly limited to 10^(-14)~10^(-12)mol/L,which cannot meet the needs for early diagnosis.On the contrary,single molecule detection allows to detect very low amount of biomarkers(~10^(-18)mol/L)through limiting the immune complex into extremely small space(below nL).The results are produced by counting positive spots.The key for this technology is to create an array of small space.After decades of development,the detection range has been successfully limited to z L(10^(-21)L)through physical isolation,nanopores,or high-resolution microscope.For now,the SiMoA based on microarray has become the gold standard for single-molecule immunoassays.And the Quanterix’s HD-1 analyzer based on SiMoA has been applied for clinical practice,while the technology based microdroplets are mainly used for laboratory research.However,the later provide an avenue for point of care testing(POCT).Herein,this review will focus on the progress of single-molecule detection based on microarrays and microdroplets.It will provide a theoretical basis for the development of ultra-high sensitivity detection methods and promote this technology into clinical applica-tions.
作者 张雪洁 汤家宝 李廷栋 葛胜祥 ZHANG Xue-jie;TANG Jia-bao;LI Ting-dong;GE Sheng-xiang(School of Public H ealth,Xiamen University,State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics,National Institute of Diagnostics and Vaccine Development in Infectious Diseases,Collaborative Innovation Centers of Biological Products,Xiamen University,Xiamen 361102,China)
出处 《中国生物工程杂志》 CAS CSCD 北大核心 2021年第4期47-54,共8页 China Biotechnology
基金 国家科技重大专项(2017ZX10302201)资助项目。
关键词 单分子免疫检测 微阵列 微液滴 Single molecule detection Microarray Microdroplets
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