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使用与纳米结构平台偶联的重组抗体检测生物标志物。

Detection of biomarkers using recombinant antibodies coupled to nanostructured platforms.

作者信息

Kierny Michael R, Cunningham Thomas D, Kay Brian K

机构信息

Department of Biological Sciences, University of Illinois at Chicago (UIC), Chicago, IL, USA.

出版信息

Nano Rev. 2012;3. doi: 10.3402/nano.v3i0.17240. Epub 2012 Jul 23.

Abstract

The utility of biomarker detection in tomorrow's personalized health care field will mean early and accurate diagnosis of many types of human physiological conditions and diseases. In the search for biomarkers, recombinant affinity reagents can be generated to candidate proteins or post-translational modifications that differ qualitatively or quantitatively between normal and diseased tissues. The use of display technologies, such as phage-display, allows for manageable selection and optimization of affinity reagents for use in biomarker detection. Here we review the use of recombinant antibody fragments, such as scFvs and Fabs, which can be affinity-selected from phage-display libraries, to bind with both high specificity and affinity to biomarkers of cancer, such as Human Epidermal growth factor Receptor 2 (HER2) and Carcinoembryonic antigen (CEA). We discuss how these recombinant antibodies can be fabricated into nanostructures, such as carbon nanotubes, nanowires, and quantum dots, for the purpose of enhancing detection of biomarkers at low concentrations (pg/mL) within complex mixtures such as serum or tissue extracts. Other sensing technologies, which take advantage of 'Surface Enhanced Raman Scattering' (gold nanoshells), frequency changes in piezoelectric crystals (quartz crystal microbalance), or electrical current generation and sensing during electrochemical reactions (electrochemical detection), can effectively provide multiplexed platforms for detection of cancer and injury biomarkers. Such devices may soon replace the traditional time consuming ELISAs and Western blots, and deliver rapid, point-of-care diagnostics to market.

摘要

生物标志物检测在未来个性化医疗领域的应用将意味着对多种人类生理状况和疾病进行早期准确诊断。在寻找生物标志物的过程中,可以针对正常组织和患病组织之间在质量或数量上存在差异的候选蛋白质或翻译后修饰生成重组亲和试剂。利用展示技术,如噬菌体展示,能够对用于生物标志物检测的亲和试剂进行可控的筛选和优化。在此,我们综述了重组抗体片段(如单链抗体和Fab片段)的应用,这些片段可从噬菌体展示文库中进行亲和筛选,以高特异性和亲和力与癌症生物标志物(如人表皮生长因子受体2(HER2)和癌胚抗原(CEA))结合。我们讨论了如何将这些重组抗体制备成纳米结构,如碳纳米管、纳米线和量子点,以便在血清或组织提取物等复杂混合物中增强对低浓度(pg/mL)生物标志物的检测。其他传感技术,如利用“表面增强拉曼散射”(金纳米壳)、压电晶体的频率变化(石英晶体微天平)或电化学反应过程中的电流产生和传感(电化学检测),可以有效地提供用于检测癌症和损伤生物标志物的多重平台。此类设备可能很快会取代传统耗时的酶联免疫吸附测定(ELISA)和蛋白质印迹法,并将快速即时诊断推向市场。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/057c/3404449/9cb297fd76f7/NANO-3-17240-g001.jpg

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