Silicon nanowire biosensor in detecting tumor markers

doi:10.3969/j.issn.2095-4344.2013.47.017

Abstract

Abstract:

BACKGROUND: Tumor markers are of great significance in early diagnosis of cancer, screening of high risk group with cancer, differential diagnosis between benign and malignant tumors, judgment of cancer progression, evaluation of cancer therapeutic effect and prediction of cancer recurrence and prognosis.
OBJECTIVE: To realize the importance of tumor marker for cancer early diagnosis by introducing the working principle and clinical application of silicon nanowires biosensor in detecting tumor markers.
METHODS: The first author searched PubMed, CNKI and Google Scholar Databases to retrieve relevant articles about tumor marker, working principle and application of silicon nanowires biosensor published from 2003 to 2013.
RESULTS AND CONCLUSION: Silicon nanowires biosensors with high sensitivity and without secondary marks show a good application prospect in detecting tumor markers. They have been used to detect tumor markers for prostate cancer, breast cancer, tumor markers of colorectal cancer, and primary liver cancer, and achieved an ideal limit of detection. However, due to the influence of debye length, most of detections can only be performed in the standard solution. There is a lack of the serum data of cancer patients.

Key words: biocompatible materials, tumor markers, biological, nanotechnology, biosensing techniques, review

CLC Number:

R318

Li Zeng-yao, Wang Tong. Silicon nanowire biosensor in detecting tumor markers[J]. Chinese Journal of Tissue Engineering Research, 2013, 17(47): 8248-8254.

Figures/Tables 7

2.6.1 前列腺癌肿瘤标记物的检测作为前列腺癌最有价值的肿瘤标记物，前列腺特异性抗原已被广泛应用于前列腺癌的筛选、早期诊断和分期上，其特异性高达97%[47-48]。2007年，Kim等[23]报道了应用n型硅纳米线生物传感器在微流体通路下对前列腺特异性抗原进行的超敏感检测。前列腺特异性抗原抗体应用3-氨丙基三乙氧基硅烷分子作为连接分子修饰到硅纳米线表面，在无需对抗原前列腺特异性抗原标记的情况下，对预先配置的不同浓度前列腺特异性抗原的标准品溶液进行检测，最终得到了前列腺特异性抗原超敏检测限<1 fg/mL。此外，作者同时指出控制硅纳米线尺寸和制作时的掺杂程度可以影响硅纳米线生物传感器的检测敏感性。遗憾的是，作者只进行了标准品溶液的检测，并没有对临床上前列腺癌患者的血清进行前列腺特异性抗原检测。 2.6.2 乳腺癌肿瘤标记物检测糖类抗原CA15-3是乳腺癌的肿瘤标记物，30%-50%的患者其指标会明显升高，CA15-3也是乳癌术后监测的最佳指标[49-50]。Stern等[26]报道了通过射流净化芯片系统和硅纳米线生物传感器的整合，应用开放性液池对全血中CA15-3进行检测。射流净化芯片系统应用抗原抗体结合原理使肿瘤标记物从全血中分离，再通过光化学裂解得到纯化的肿瘤标记物，最后把纯化的肿瘤标记物转移到硅纳米线生物传感器中进行检测。Stern等获得CA15-3在全血中的检测值为30 U/mL。此检测方法能够克服硅纳米线生物传感器检测血清样本时非肿瘤标记物分子的非特异性绑定作用，增加传感器应用的临床相关性。但其纯化过程较为繁琐，相当于对肿瘤标记物进行了一次标记。 2.6.3 结直肠癌肿瘤标记物检测癌胚抗原为结直肠癌的辅助诊断指标，其为正常胚胎组织所产生的成分，出生后逐渐消失，或仅存极微量。当细胞癌变时，此类抗原表达可明显增多。Zheng等[22]报道了应用硅纳米线生物传感器阵列在微流体通路下对癌胚抗原、前列腺特异性抗原、mucin-1三种肿瘤标记物配置液进行的同时多路复用检测。凭借该更为敏感的检测方法，Zheng等得到癌胚抗原的检测限为0.9 pg/mL。然而作者同样没有在血清样本中完成对癌胚抗原的检测。 2.6.4 原发性肝癌的肿瘤标记物检测甲胎蛋白为一种糖蛋白，正常情况下，这种蛋白主要来自胚胎的肝细胞，胎儿出生约两周后甲胎蛋白从血液中消失，是诊断原发性肝癌的特异性肿瘤标记物，具有确立诊断、早期诊断、鉴别诊断的作用[51]。Ivanov等[46]报道了应用n型硅纳米线生物传感器在开放性液池下对甲胎蛋白标准品溶液进行检测，得到了10- 15 mol/L的检测限。然而，作者同样没有进行血清样本的检测。 2.6.5 其他肿瘤标记物的检测血管内皮生长因子属血小板源性生长因子家族的生长因子，其能增加血管通透性，并具有血管生成功能[53]。恶性肿瘤的生长代谢、浸润转移和复发均与肿瘤的血供密切相关。因此，血管内皮生长因子作为一种广谱的肿瘤标记物对多种肿瘤的辅助诊断均有重要的临床价值，且对初诊肿瘤患者，血管内皮生长因子也是一个良好的检测指标。人类C-反应蛋白是感染和组织损伤时血浆浓度快速，急剧升高的主要急性期蛋白，恶性肿瘤患者C-反应蛋白大都升高，如C-反应蛋白与甲胎蛋白的联合检测，可用于肝癌与肝脏良性疾病的鉴别诊断，并且，C-反应蛋白测定用于肿瘤的治疗和预后都有积极意义。Lee等[24]报道了应用n型和p型硅纳米线生物传感器在开放性液池下分别对血管内皮生长因子标准品液进行检测，其得到的检测限为n型1.04 nmol/L，p型104 pmol/L。而Jung等[17]报到的应用p型硅纳米线生物传感器在微流体通路下对C-反应蛋白标准品液的检测，得到C-反应蛋白的超敏感检测限为1 fmol/L。同样遗憾的是这两次检测都没有在血清样本下进行。"

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