Detection of Glial Fibrillary Acidic Protein in Patient Plasma Using On-Chip Graphene Field-Effect Biosensors, in Comparison with ELISA and Single-Molecule Array.
Detection of Glial Fibrillary Acidic Protein in Patient Plasma Using On-Chip Graphene Field-Effect Biosensors, in Comparison with ELISA and Single-Molecule Array.
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DOI：
10.1021/acssensors.1c02232
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发表时间：
2022-01-28
期刊：
影响因子：
8.9
通讯作者：
Li B
中科院分区：
文献类型：
--
作者：
Xu L;Ramadan S;Akingbade OE;Zhang Y;Alodan S;Graham N;Zimmerman KA;Torres E;Heslegrave A;Petrov PK;Zetterberg H;Sharp DJ;Klein N;Li B
胶质原纤维酸性蛋白（GFAP）是许多神经系统疾病（如创伤性脑损伤）的特异性血液生物标志物。使用生物传感器检测缓冲溶液中的GFAP已得到证实，但尚未报道患者样品中GFAP的准确定量，但迫切需要。在此，我们展示了一种强大的片上石墨烯场效应晶体管（GFET）生物传感方法，用于灵敏和超快地检测患者血浆中的GFAP。梅奥分类法定义的中重度创伤性脑损伤患者被招募提供血浆样本。靶GFAP与偶联在单层GFET器件上的特异性抗体结合，触发其Dirac点的移位，这种信号变化与患者血浆中GFAP浓度相关。该方法在缓冲液中的检出限为20 fg/mL (400 aM)，在患者血浆中的检出限为231 fg/mL （4 fM）。同时，我们首次将我们的结果与最先进的单分子阵列（Simoa）技术和经典的酶联免疫吸附试验（ELISA）进行比较，以供参考。GFET生物传感器对Simoa具有竞争力的LOD （1.18 pg/mL）和更快的样品到结果时间（<15 min），并且它更便宜，更用户友好。与ELISA相比，GFET具有总检测时间、检测灵敏度和简便等优点。这种GFET生物传感平台对GP手术和患者家庭的创伤性脑损伤的即时诊断和监测具有很高的前景。
Glial fibrillary acidic protein (GFAP) is a discriminative blood biomarker for many neurological diseases, such as traumatic brain injury. Detection of GFAP in buffer solutions using biosensors has been demonstrated, but accurate quantification of GFAP in patient samples has not been reported, yet in urgent need. Herein, we demonstrate a robust on-chip graphene field-effect transistor (GFET) biosensing method for sensitive and ultrafast detection of GFAP in patient plasma. Patients with moderate–severe traumatic brain injuries, defined by the Mayo classification, are recruited to provide plasma samples. The binding of target GFAP with the specific antibodies that are conjugated on a monolayer GFET device triggers the shift of its Dirac point, and this signal change is correlated with the GFAP concentration in the patient plasma. The limit of detection (LOD) values of 20 fg/mL (400 aM) in buffer solution and 231 fg/mL (4 fM) in patient plasma have been achieved using this approach. In parallel, for the first time, we compare our results to the state-of-the-art single-molecule array (Simoa) technology and the classic enzyme-linked immunosorbent assay (ELISA) for reference. The GFET biosensor shows competitive LOD to Simoa (1.18 pg/mL) and faster sample-to-result time (<15 min), and also it is cheaper and more user-friendly. In comparison to ELISA, GFET offers advantages of total detection time, detection sensitivity, and simplicity. This GFET biosensing platform holds high promise for the point-of-care diagnosis and monitoring of traumatic brain injury in GP surgeries and patient homes.
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