[论文解读] Ultrasensitive Real-Time Detection of SARS-CoV-2 Proteins with Arrays of Biofunctionalized Graphene Field-Effect Transistors
本工作展示了在单芯片集成的自动微流控系统中,通过一组生物功能化石墨烯场效应晶体管阵列,进行实时的SARS-CoV-2刺突蛋白与核衣壳蛋白的多路检测,达到阿摩尔级灵敏度。
With the growing interest in graphene field-effect transistors (GFETs) for biosensing applications, there is a strong demand for strategies enabling flexible and multiplexed biofunctionalization, as well as highly parallel, real-time electronic readout integrated with microfluidic control. Here we present a methodology that addresses these challenges by enabling real-time, parallel monitoring of multiple GFETs integrated on a single microfabricated chip within an automated electronic and microfluidic platform. We demonstrate the capabilities of this approach through ultrasensitive detection of the SARS-CoV-2 spike (S) and nucleocapsid (N) proteins. GFET chips are functionalized via van der Waals assembly using 1 nm-thick molecular two-dimensional (2D) materials - carbon nanomembranes - which enable multiplexed biofunctionalization. The chips are integrated into a custom-developed microelectronic and microfluidic system that allows parallel, real-time, and automated measurements of 15 GFETs. We present in situ biofunctionalization of the GFETs with antibodies, followed by highly specific detection of the S- and N-proteins with limits of detection down to 10 aM and a dynamic range spanning four orders of magnitude. Owing to its versatility, the presented methodology is readily adaptable for sensing a wide range of biological and chemical targets.
研究动机与目标
- 满足对GFETs进行灵活多路生物功能化以用于生物传感的需求。
- 开发一个与微流控整合在单芯片上的并行、实时电子读出平台。
- 利用GFETs的多重功能化实现对S和N蛋白的超灵敏检测。
提出的方法
- 使用范德瓦尔斯组装将GFET功能化为1 nm厚的碳纳米薄膜,以实现多路生物功能化。
- 将GFET芯片与自定义电子学和微流控系统集成,实现15个GFET的并行、实时测量。
- 原位进行抗S和N蛋白的生物功能化,然后进行检测。
- 实现下限达到10 aM,且动态范围跨越四个数量级。
实验结果
研究问题
- RQ1单芯片上的生物功能化GFET阵列能否提供对SARS-CoV-2蛋白的实时多路检测?
- RQ2使用该平台可达到的S和N蛋白的检测下限和动态范围是多少?
- RQ3范德瓦尔斯组装的碳纳米薄膜功能化是否与自动化微流控集成的并行读出兼容?
主要发现
- 在一个自动化平台中对15个GFET进行实时、并行监测。
- 原位生物功能化,使用抗体实现对SARS-CoV-2 S和N蛋白的特异性检测。
- 目标蛋白的检测下限达到10 aM。
- 动态范围跨越四个数量级。
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