Abstract：
Traumatic brain injury (TBI) is widely recognized as a global public health crisis, affecting millions of people each year, leading to permanent neurologic, emotional, and occupational disability, and highlighting the urgent need for rapid, sensitive, and early assessment. Here, we design a novel and simple lithography-free method for preparing dual-channel graphene-based field-effect transistors (G-FETs) and integrating them with microfluidic channels for simultaneously multiplexed detection of key blood TBI biomarkers: neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP). The G-FET utilizes an ingenious dual-channel electrode array design, where the source is shared between channels and the drains are independent of each other, which is the key to achieving simultaneous output of dual detection signals. At the same time, the microfluidic chip realizes microscale fluidic control and fast sample response time. This integrated detection system shows excellent sensitivity in biological fluids for the TBI biomarkers with detection limits as low as 55.63 fg/mL for NFL and 144.45 fg/mL for GFAP in phosphate-buffered saline (PBS) buffer, respectively. Finally, the clinical sample analysis shows promising performance for TBI detection, with an area under the curve (AUC) of 0.98 for the two biomarkers. And the combined dual-protein assay is also a good predictor of intracranial injury findings on computed tomography (CT) scans (AUC = 0.907). The integrated microfluidic G-FET device with a dual-signal output strategy has important potential for application in clinical practice, providing more comprehensive information for brain injury assessment.
摘要：
创伤性脑损伤(TBI)是公认的全球性公共卫生危机,每年影响数百万人，导致永久性神经学，情感,和职业残疾，并强调迫切需要快速，敏感,早期评估。这里,我们设计了一种新颖且简单的无光刻方法，用于制备基于石墨烯的双通道场效应晶体管（G-FET），并将其与微流体通道集成，以同时多路检测关键的血液TBI生物标志物：神经丝轻链（NFL）和胶质纤维酸性蛋白（GFAP）。G-FET采用巧妙的双通道电极阵列设计，其中源在通道之间共享，并且排水管彼此独立，这是实现双检测信号同时输出的关键。同时,微流控芯片实现了微尺度的流体控制和快速的样品响应时间。这种集成的检测系统在生物流体中对TBI生物标志物具有出色的灵敏度，在磷酸盐缓冲盐水（PBS）缓冲液中，NFL的检出限低至55.63fg/mL，GFAP的检出限低至144.45fg/mL。分别。最后,临床样本分析显示了TBI检测的良好性能，两种生物标志物的曲线下面积(AUC)为0.98。并且组合的双蛋白测定也是计算机断层扫描（CT）扫描（AUC=0.907）的颅内损伤发现的良好预测指标。具有双信号输出策略的集成微流体G-FET器件在临床实践中具有重要的应用潜力，为脑损伤评估提供更全面的信息。
