石墨烯基生物半导体构建无标记生物传感器及在肿瘤早期诊断中的应用研究

In this project, biological semiconductors will be employed for the study, which are developed by the combination of antibody or other bio-recognition units with graphene. Due to the excellent electrical conductivity and electrical percolation of graphene, the electric resistance of biological semiconductor will reduce with the concentration increasing of graphene. There is a percolation concentration for graphene in the process. And the electric resistance of biological semiconductor will decrease sharply around the percolation concentration. Based on this feature, a novel label-free biosensor can be fabricated by biological semicaonductor, which will be immobilized onto some specific substrates to form membrane with three-dimensional network structure. The sensitive tumor-diagnosis is relied on the remarkable resistance change of the membrane after the capture of tumor marker. The suggested method can realize the on-site detection of tumor markers without labeling while simply through measuring the resistance change before and after binding targets by biological semiconductor, which fits well with the guidance established by World Health Organization for developing point-of-care diagnostic tests in resource-poor settings. Biological semiconductor chip can be developed by the integration of many biosensors onto one chip, which can be used for the high-throughput, high specific and simultaneous detection of one or multiple tumor markers. As a result, POCT can be set up for the early-diagnosis, screening and prognosis monitor of various tumors in resource-poor regions in our country.

本项目拟利用具有优异导电性及电渗流特性的石墨烯与抗体等生物识别体结合构建生物半导体，其电阻在随石墨烯的浓度增大而降低的过程中存在着一个突跃浓度，生物半导体电阻在该浓度附近会呈现出显著降低的规律。基于这一特性，可以将石墨烯固定抗体等所构成的生物半导体修饰在特定基底上形成具有三维网络结构的薄膜，将其作为传感单元构建无标记型生物传感器，利用这种新型传感器捕获肿瘤标志物引起薄膜电阻显著改变来实现对肿瘤的高灵敏诊断。本项目所提出的方法仅通过测量电阻在生物半导体结合识别对象前后电阻变化，无需标记即可实现肿瘤标志物现场灵敏检测，符合世界卫生组织提出的针对医疗资源缺乏区域开发POCT医疗诊断平台的指南。基于传感器制备简单的特点，能够有效地将多个传感器整合到芯片上，制得生物半导体芯片，应用到单一或多个肿瘤标志物高通量特异性共时检测，开发出针对我国医疗资源贫乏地区肿瘤早期诊断、筛查及预后监测的POCT平台。

癌症的早期诊断对于其治疗起着极为重要的作用。我国农村和西部等区医疗设备及医务工作者匮乏地区癌症死亡率的上升速度明显高于城市，为此类地区病患提供简单、便捷、准确的肿瘤早期诊断就显得尤为重要。本项目建立了一种基于优异导电性及电渗流特性的石墨烯基纳米材料与抗体等生物识别体结合所得生物半导体，其电阻随石墨烯的浓度增大而降低的过程中存在着一个突变浓度，生物半导体电阻在该浓度附近会呈现出显著降低的规律。我们成功利用此类生物半导体构建了无标记型生物传感器，通过测定结合肿瘤标志物前后生物半导体电阻的显著变化，实现了对以肝癌典型标志物为对象的灵敏检测。该技术可进一步发展成为适用于我国医疗资源贫乏地区肿瘤筛查与早期诊断的技术平台。在一年期的项目研究中，我们初步构建了基于石墨烯基生物半导体的具有高灵敏的蛋白类肿瘤标志物定量检测特性的薄膜电阻型生物传感器。项目组共有9名研究人员，先后在著名刊物发表3篇高质量SCI论文（累计影响因子16.311；单篇平均影响因子5.437），其中项目承担人以通讯作者或第一作者身份在本领域一区SCI刊物发表论文2篇，为Biosensors & Bioelectronics (影响因子 5.437; 2篇)。研究成果获得了同行的关注，据ISI检索引用次数达9。项目的实施不仅取得了令人满意的研究结果，同时培养了2名生物分析检测专业人才，并获得了一定的社会影响，基本达到预期成果。