纳米复合材料修饰的电化学传感器的CA125快速检测
|
摘要
提出了一种利用多壁碳纳米管(MWCNT)、硫堇(THI)和纳米金(AuNP)纳米复合材料固定在电化学传感器表面进行肿瘤标志物CA125快速检测的电化学免疫新方法。该方法检测原理是利用CA125抗原和抗体结合后形成的免疫复合物影响纳米复合材料中THI电子转移,从而使不同浓度CA125抗原的检测电流响应随着其浓度的增加而下降。采用循环伏安法(CV)和差分脉冲伏安法(DPV)对电化学传感器的电化学特性进行测试。测试结果表明:在1.3～130 U/mL浓度内,CA125抗原的DPV峰值电流响应与其浓度对数之间呈现良好的线性关系,线性相关系数为0.991。采用该方法对三例质控人血清样本进行检测,与酶联免疫吸附(ELISA)法相比,相对误差值小于5.12%。该方法在检测之前不需要对检测样本进行预处理,且检测时间较短、成本较低、检测精度较高,可广泛应用于其他肿瘤标志物的检测。
A new electrochemical immune method for rapid testing of tumor marker CA125 was proposed by immobilizing nanocomposites of the multiwalled carbon nanotube(MWCNT),thionine(THI)and gold nanoparticle(AuNP)on the surface of the electrochemical sensor.The testing principle of the method is that the immune complex formed by the combination of CA125 antigen and antibody affects the electron transfer of THI,then the detection current responses to different concentrations of CA125 antigen decrease with the increase of the CA125 antigen concentration.Cyclic voltammetry(CV)and differential pulse voltammetry(DPV)were adopted to test the electrochemical property of the electrochemical sensor.The testing results show that the DPV peak current response of the CA125 antigen has good linear relationship with the logarithm of the CA125 concentration in the concentration range from1.3 U/mL to 130 U/mL,and the linear correlation coefficient is 0.991.Compared with the enzyme-linked immunosorbent assay(ELISA)method,the relative error value obtained by the method is less than 5.12%for three qulity control human serum samples.Due to no pretreatment,short testing time,lowcost and high testing accuracy,the method can be widely used for the testing of other tumor markers.
A new electrochemical immune method for rapid testing of tumor marker CA125 was proposed by immobilizing nanocomposites of the multiwalled carbon nanotube(MWCNT),thionine(THI)and gold nanoparticle(AuNP)on the surface of the electrochemical sensor.The testing principle of the method is that the immune complex formed by the combination of CA125 antigen and antibody affects the electron transfer of THI,then the detection current responses to different concentrations of CA125 antigen decrease with the increase of the CA125 antigen concentration.Cyclic voltammetry(CV)and differential pulse voltammetry(DPV)were adopted to test the electrochemical property of the electrochemical sensor.The testing results show that the DPV peak current response of the CA125 antigen has good linear relationship with the logarithm of the CA125 concentration in the concentration range from1.3 U/mL to 130 U/mL,and the linear correlation coefficient is 0.991.Compared with the enzyme-linked immunosorbent assay(ELISA)method,the relative error value obtained by the method is less than 5.12%for three qulity control human serum samples.Due to no pretreatment,short testing time,lowcost and high testing accuracy,the method can be widely used for the testing of other tumor markers.
引文
[1]ROSEN D G,WANG L,ATKINSON J N,et al.Potential markers that complement expression of CA125 in epithelial ovarian cancer[J].Gynecologic Oncology,2005,99(2):267-277.
[2]GUBE M,TAEGER D,WEBER D G,et al.Performance of biomarkers SMRP,CA125,and CYFRA21-1 as potential tumor markers for malignant mesothelioma and lung cancer in a cohort of workers formerly exposed to asbestos[J].Archives of Toxicology,2011,85(3):185-192.
[3]NORUM L F,ERIKSTEIN B,NUSTAD K.Elevated CA125in breast cancer-a sign of advanced disease[J].Tumor Biology,2001,22(4):223-228.
[4]NGUYEN L,CARDENAS-GOICOECHEA S J,GORDON P,et al.Biomarkers for early detection of ovarian cancer[J].Women's Health,2013,9(2):171-187.
[5]BIAN J,SUN X X,LI B,et al.Clinical significance of serum HE4,CA125,CA724,and CA19-9in patients with endometrial cancer[J].Technology in Cancer Research&Treatment,2016,16(4):435-439.
[6]LI J P,XU Q,FU C,et al.A dramatically enhanced electrochemiluminescence assay for CA125 based on dendrimer multiply labeled luminol on Fe3O4nanoparticles[J].Sensors and Actuators:B,2013,185:146-153.
[7]何俊民.CA125 RIA在非卵巢癌上的应用[J].放射免疫学杂志,1993,5:320-321.
[8]MCINTOSH M W,DRESCHER C,KARLAN B,et al.Combining CA125 and SMR serum markers for diagnosis and early detection of ovarian carcinoma[J].Gynecologic Oncology,2004,95(1):9-15.
[9]KIM Y M,WHANG D H,PARK J,et al.Evaluation of the accuracy of serum human epididymis protein 4 in combination with CA125 for detecting ovarian cancer:aprospective casecontrol study in a korean population[J].Clinical Chemistry and Laboratory Medicine,2011,49(3):527-534.
[10]CHU W R,CHEN Y,LIU W,et al.Paper-based chemiluminescence immunodevice with temporal controls of reagent transport techinque[J].Sensors and Actuators:B,2017,250:324-332.
[11]FAN Y,LIU J T,WANG Y,et al.A wireless point-of-care testing system for the detection of neuron-specific enolase with microfluidic paper-based analytical devices[J].Biosensors and Bioelectronics,2017,95:60-66.
[12]ABOUTALEBI S H,CHIDEMBO A T,SALARI M,et al.Comparison of GO,GO/MWCNTs composite and MWCNTs as potential electrode materials for supercapacitors[J].Energy&Environmental Science,2011,4(5):1855-1865.
[13]陈雯雯,李唐松,何沙,等.微流控及纳米金应用于免疫检测的最新研究进展[J].中国科学:化学,2011,41(10):1660.
[14]JIA X L,LIU Z M,LIU N,et al.A label-free immunosensor based on graphene nanocomposites for simultaneous multiplexed electrochemical determination of tumor markers[J].Biosensors and Bioelectronics,2014,53:160-166.
[15]WANG Y,XU H R,LUO J P,et al.A novel label-free microfluidic paper-based immunosensor for highly sensitive electrochemical detection of carcinoembryonic antigen[J].Biosensors and Bioelectronics,2016,83:319-326.
[2]GUBE M,TAEGER D,WEBER D G,et al.Performance of biomarkers SMRP,CA125,and CYFRA21-1 as potential tumor markers for malignant mesothelioma and lung cancer in a cohort of workers formerly exposed to asbestos[J].Archives of Toxicology,2011,85(3):185-192.
[3]NORUM L F,ERIKSTEIN B,NUSTAD K.Elevated CA125in breast cancer-a sign of advanced disease[J].Tumor Biology,2001,22(4):223-228.
[4]NGUYEN L,CARDENAS-GOICOECHEA S J,GORDON P,et al.Biomarkers for early detection of ovarian cancer[J].Women's Health,2013,9(2):171-187.
[5]BIAN J,SUN X X,LI B,et al.Clinical significance of serum HE4,CA125,CA724,and CA19-9in patients with endometrial cancer[J].Technology in Cancer Research&Treatment,2016,16(4):435-439.
[6]LI J P,XU Q,FU C,et al.A dramatically enhanced electrochemiluminescence assay for CA125 based on dendrimer multiply labeled luminol on Fe3O4nanoparticles[J].Sensors and Actuators:B,2013,185:146-153.
[7]何俊民.CA125 RIA在非卵巢癌上的应用[J].放射免疫学杂志,1993,5:320-321.
[8]MCINTOSH M W,DRESCHER C,KARLAN B,et al.Combining CA125 and SMR serum markers for diagnosis and early detection of ovarian carcinoma[J].Gynecologic Oncology,2004,95(1):9-15.
[9]KIM Y M,WHANG D H,PARK J,et al.Evaluation of the accuracy of serum human epididymis protein 4 in combination with CA125 for detecting ovarian cancer:aprospective casecontrol study in a korean population[J].Clinical Chemistry and Laboratory Medicine,2011,49(3):527-534.
[10]CHU W R,CHEN Y,LIU W,et al.Paper-based chemiluminescence immunodevice with temporal controls of reagent transport techinque[J].Sensors and Actuators:B,2017,250:324-332.
[11]FAN Y,LIU J T,WANG Y,et al.A wireless point-of-care testing system for the detection of neuron-specific enolase with microfluidic paper-based analytical devices[J].Biosensors and Bioelectronics,2017,95:60-66.
[12]ABOUTALEBI S H,CHIDEMBO A T,SALARI M,et al.Comparison of GO,GO/MWCNTs composite and MWCNTs as potential electrode materials for supercapacitors[J].Energy&Environmental Science,2011,4(5):1855-1865.
[13]陈雯雯,李唐松,何沙,等.微流控及纳米金应用于免疫检测的最新研究进展[J].中国科学:化学,2011,41(10):1660.
[14]JIA X L,LIU Z M,LIU N,et al.A label-free immunosensor based on graphene nanocomposites for simultaneous multiplexed electrochemical determination of tumor markers[J].Biosensors and Bioelectronics,2014,53:160-166.
[15]WANG Y,XU H R,LUO J P,et al.A novel label-free microfluidic paper-based immunosensor for highly sensitive electrochemical detection of carcinoembryonic antigen[J].Biosensors and Bioelectronics,2016,83:319-326.