Centre for Personalised Nanomedicine, Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Corner College and Cooper Roads (Bldg 75), Brisbane, QLD, 4072, Australia.
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, 4072, Australia.
Small. 2017 Mar;13(9). doi: 10.1002/smll.201602902. Epub 2016 Dec 22.
Cancer diagnosis and patient monitoring require sensitive and simultaneous measurement of multiple cancer biomarkers considering that single biomarker analysis present inadequate information on the underlying biological transformations. Thus, development of sensitive and selective assays for multiple biomarker detection might improve clinical diagnosis and expedite the treatment process. Herein, a microfluidic platform for the rapid, sensitive, and parallel detection of multiple cancer-specific protein biomarkers from complex biological samples is presented. This approach utilizes alternating current electrohydrodynamic-induced surface shear forces that provide exquisite control over fluid flow thereby enhancing target-sensor interactions and minimizing non-specific binding. Further, the use of surface-enhanced Raman scattering-based spectral encoding with individual barcodes for different targets enables specific and simultaneous detection of captured protein biomarkers. Using this approach, the specific and sensitive detection of clinically relevant biomarkers including human epidermal growth factor receptor 2 (HER2); Mucin 1, cell surface associated (MUC1); epidermal growth factor receptor; and Mucin 16, cell surface associated (MUC16) at concentrations as low as 10 fg mL in patient serum is demonstrated. Successful target detection from patient samples further demonstrates the potential of this current approach for the clinical diagnosis, which envisages a clinical translation for a rapid and sensitive appraisal of clinical samples in cancer diagnostics.
癌症诊断和患者监测需要敏感且同时测量多种癌症生物标志物，因为单一生物标志物分析提供的关于潜在生物学转化的信息不足。因此，开发用于多种生物标志物检测的敏感和选择性测定法可能会改善临床诊断并加速治疗过程。在此，提出了一种用于从复杂生物样品中快速、敏感和并行检测多种癌症特异性蛋白质生物标志物的微流控平台。该方法利用交流电动流体动力诱导的表面剪切力，对流体流动进行精密控制，从而增强目标-传感器相互作用并最小化非特异性结合。此外，使用基于表面增强拉曼散射的光谱编码和针对不同靶标的单个条形码，可实现捕获的蛋白质生物标志物的特异性和同时检测。使用这种方法，可以在患者血清中低至 10 fg/mL 的浓度下特异性和敏感地检测到包括人表皮生长因子受体 2 (HER2)、黏蛋白 1，细胞表面相关 (MUC1)、表皮生长因子受体和黏蛋白 16，细胞表面相关 (MUC16) 在内的临床相关生物标志物。从患者样本中成功检测到目标进一步证明了这种方法在临床诊断中的应用潜力，这预示着该方法可用于快速和敏感地评估癌症诊断中的临床样本。
