Application of high sensitive detection sensor chip in detection of brain glioma disease
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摘要: 太赫兹波因其指纹谱识别和无损探测等特性可被应用于物质的快速定性与定量识别。现阶段太赫兹技术方法对物质含量检测的下限在毫克量级,然而实际生物医学样本中待测物的浓度通常在微克量级甚至以下,现有方法限制了其检测灵敏度和可行性。研究中以脑胶质瘤里的特异性物质肌醇(MI)和γ-氨基丁酸(GABA)为例,基于电容电感效应,设计了一款增强太赫兹检测灵敏度的超材料芯片。然后通过测试MI和GABA在不同浓度下的太赫兹光谱,证明其各自随着浓度的变化,芯片谐振峰频移呈现不同的规律,从而进行有效的定性识别,且对于MI和GABA的已知样品,可以根据频移规律实现定量分析。根据实验数据计算可得,所设计的芯片对这两种样品含量检测下限分别为3.457 µg和2.552 µg,与传统压片法的检测极限相比提高了三个数量级。这些结果对后期生物医学中定性和定量检测疾病的微量特异性物质具有重要参考价值。Abstract: Terahertz wave can be applied to the rapid qualitative and quantitative identification of substances because of its characteristics of fingerprint identification and non-destructive detection. At present, the detection limit of terahertz technology is in the order of milligram. However, the concentration of the tested substance in the actual biomedical samples is usually in the order of microgram or even below, which limits the detection sensitivity and feasibility. In this study, by taking the glioma biomarkers: inositol (MI) and gamma aminobutyric acid (GABA) as an example, based on the inductive-capacitive (LC) resonance, a metamaterial chip was designed to enhance THz detection sensitivity. Then, the terahertz spectra of the chip covered by MI and GABA at different concentrations was tested to prove that their resonance frequency shifts show different rules with the change of concentration, basing on which the qualitative identification could be achieved. And for known samples of MI and GABA, quantitative analysis could be achieved according to the frequency shifts law. According to calculations based on experimental data, the lower detection limits of proposed chip for these two samples are 3.457 µg and 2.552 µg, respectively, which are three orders of magnitude higher than the detection limit of the conventional tableting method. These results have important reference value for the qualitative and quantitative detection of trace specific substances of diseases in later biomedicine.
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Key words:
- metamaterial sensor chip /
- terahertz /
- high sensitivity detection /
- brain glioma disease
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图 4 MI的测试结果。(a)不同浓度MI覆盖的超材料芯片的太赫兹光谱;(b)不同浓度MI下芯片谐振峰频移变化。测量误差棒标于各自曲线/点上
Figure 4. Testing results of MI. (a) Terahertz spectra of MI covered metamaterial chips with different concentrations; (b) The change of formant frequency shift of chip under different concentration of MI. The error bars are marked on the curves/points
图 5 GABA的测试结果。(a)不同GABA浓度覆盖的超材料芯片的太赫兹光谱;(b)不同GABA浓度下芯片谐振峰频移变化。测量误差棒标于各自曲线/点上
Figure 5. Testing results of GABA. (a) Terahertz spectra of metamaterial chips covered with different concentrations of GABA; (b) The change of formant frequency shift of chip under different concentrations of GABA.The error bars are marked on the curves/points
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[1] Li Can, Wang Xin, Zhai Shuang. Detection of diseased brain based on medical image [J]. Journal of Changchun University of Technology, 2020, 41(2): 162-167. (in Chinese) doi: 10.15923/j.cnki.cn22-1382/t.2020.2.10 [2] Wang Y Y, Wang L P, Li T, et al. Terahertz characteristic absorption spectrum analysis of homocysteine [J]. Acta Optica Sinica, 2019, 39(10): 1030003. (in Chinese) doi: 10.3788/AOS201939.1030003 [3] Xie Q, Yang H R, Li H G, et al. Explosives identification based on terahertz time domain spectroscopy [J]. Optical Precision Engineering, 2016, 24(10): 2392-2399. (in Chinese) doi: 10.3788/OPE.20162410.2392 [4] Wang S F, Wang Q C, Peng Y. Mechanism study of terahertz radiation regulation in multi-color laser field [J]. Journal of the Optical Society of America B, 2020, 37(11): 3325-3334. (in Chinese) doi: 10.1364/JOSAB.399626 [5] Yan Jun, Wang Liping, Li Tian, et al. Quantitative identification of homocysteine in liquid by terahertz technology [J]. Infrared and Laser Engineering, 2019, 48(8): 0819001. (in Chinese) doi: 10.3788/IRLA201948.0819001 [6] Zhang J F, Yuan X D, Qin S Q. Tunable terahertz and optical metamaterials [J]. Chinese Journal of Optics, 2014, 7(3): 349-364. (in Chinese) doi: 10.3788/CO.20140703.0349 [7] Zhu Y M, Shi C J, Wu X, et al. Research on algorithm of terahertz spectroscopy in biomedical detection [J]. Acta Optica Sinica, 2020, 41(1): 0130001. (in Chinese) [8] Gao Xiang, Liu Xiaoqing, Dai Zijie, et al. Integrated terahertz confocal imaging system based on waveguide structure [J]. Infrared and Laser Engineering, 2019, 48(S2): S219001. (in Chinese) doi: 10.3788/IRLA201948.S219001 [9] Peng Y, Yuan X R, Zou X, et al. Terahertz identification and quantification of neurotransmitter and neurotrophy mixture [J]. Biomedical Optics Express, 2016, 7(11): 4472-4479. (in Chinese) doi: 10.1364/BOE.7.004472 [10] Bianch L, Micheli E D, Bricolo A, et al. Extracellular levels of amino acids and choline in human high grade gliomas: An intraoperative microdialysis study [J]. Neurochemical Research, 2004, 29(1): 325-334. doi: 10.1023/B:NERE.0000010462.72557.6d [11] Choi I Y, Lee S P, Merkle H, et al. In vivo detection of gray and white matter differences in GABA concentration in the human brain [J]. Neurolmage, 2006, 33(1): 85-93. doi: 10.1016/j.neuroimage.2006.06.016 [12] Gu H Y, Shi C J, Wu X, et al. Molecular methylation detection based on terahertz metamaterial technology [J]. Analyst, 2020, 145(20): 6705-6712. doi: 10.1039/D0AN01062F [13] Wang L P, Wu X, Peng Y, et al. Quantitative analysis of homocysteine in liquid by terahertz spectroscopy [J]. Biomedical Optics Express, 2020, 11(5): 2570-2577. (in Chinese) doi: 10.1364/BOE.391894 [14] Pan X C, Yao Z H, Xu X L, et al. Fabrication, design and application of THz metamaterials [J]. Chinese Optics, 2013, 6(3): 283-296. (in Chinese) [15] Guo L H, Wang X K, Zhang Y. Terahertz digital holographic imaging of biological tissue [J]. Optical Precision Engineering, 2017, 25(3): 611-615. (in Chinese) doi: 10.3788/OPE.20172503.0611 [16] Luo C W, Zhao Z Y, Song Z Q, et al. Terahertz extraodinary transmission from flexible C-shape split-ring resnoators [J]. Journal of East China Normal University (Natural Science), 2016, 6(1): 0107-06. (in Chinese) [17] Singh R, Cao W, Al-Naib I, et al. Ultrasensitive terahertz sensing with high-Q Fano resonances in metasurfaces [J]. Applied Physics Letters, 2014, 105(170): 171101. [18] Peng Y, Shi C J, Zhu Y M, et al. Qualitative and quantitative analysis algorithm of terahertz apectroscopy in biomedical detection [J]. Chinese Journal of Lasers, 2019, 46(6): 0614002. (in Chinese) doi: 10.3788/CJL201946.0614002