Alzghoul Salah, Hailat Mohammad, Zivanovic Sandra, Que Long, Shah Girish V
Louisiana Tech University, United States.
University of Louisiana-Monroe, United States.
Biosens Bioelectron. 2016 Mar 15;77:491-8. doi: 10.1016/j.bios.2015.10.006. Epub 2015 Oct 9.
Currently used cancer marker for prostate adenocarcinoma (PC), serum prostate-specific antigen (PSA), greatly overestimates PC population. Patients with high PSA levels have to undergo unnecessary but physically painful and expensive procedure such as prostate biopsies repeatedly. The reliability of PC test can be greatly increased by finding a protein that is secreted selectively by malignant, but not normal, prostate cells. A recently discovered novel protein, referred as neuroendocrine marker (NEM), is secreted only by malignant prostate cells and released in blood circulation. Although NEM seems to be significantly more reliable based on the data obtained from a limited cohort, currently available NEM ELISA is not suitable for undertaking a large study. Therefore, the goal of the present study was to develop an alternative, label-free assay system that can reliably measure NEM and PSA in patient samples. Herein an optofluidic chip that can reliably detect PSA as well as NEM in patient samples has been developed. The optofluidic chip, which consists of arrayed nanopore-based sensors fabricated from anodic aluminum oxide (AAO) thin film, offers improved sensitivity upon the optimization of the concentration of the detector antibodies immobilized on the sensor surface. The results demonstrate that the chip is reliable, extremely sensitive and requires just 1 µl of patient serum (or even less) to measure PSA and NEM even in a non-cancer individual. Compared with the traditional ELISA for PSA, the nanopore-based sensor assay is 50-100 fold more sensitive, and offers many advantages such as elimination of labeled antigen, need for sophisticated equipment and highly trained individuals. These advantages, along with the low cost, should make the technology suitable for point-of-care application to screen elderly male populations for PC and to monitor the progress of patients undergoing PC treatment.
目前用于前列腺腺癌(PC)的癌症标志物——血清前列腺特异性抗原(PSA),会大大高估PC患者群体。PSA水平高的患者不得不反复接受不必要但身体痛苦且昂贵的检查,如前列腺活检。通过找到一种仅由恶性前列腺细胞而非正常前列腺细胞选择性分泌的蛋白质,PC检测的可靠性可大幅提高。最近发现的一种新型蛋白质,称为神经内分泌标志物(NEM),仅由恶性前列腺细胞分泌并释放到血液循环中。尽管根据从有限队列获得的数据,NEM似乎明显更可靠,但目前可用的NEM酶联免疫吸附测定(ELISA)不适用于进行大规模研究。因此,本研究的目标是开发一种替代的、无标记的检测系统,该系统能够可靠地测量患者样本中的NEM和PSA。在此,已开发出一种能够可靠检测患者样本中PSA以及NEM的光流体芯片。该光流体芯片由基于阳极氧化铝(AAO)薄膜制造的阵列纳米孔传感器组成,在优化固定在传感器表面的检测抗体浓度后,灵敏度得到提高。结果表明,该芯片可靠、极其灵敏,即使对于非癌症个体,测量PSA和NEM时仅需1微升患者血清(甚至更少)。与传统的PSA ELISA相比,基于纳米孔的传感器检测灵敏度高50至100倍,并且具有许多优点,如无需标记抗原、无需复杂设备以及无需训练有素的人员。这些优点,再加上低成本,应使该技术适用于即时检测应用,以筛查老年男性群体中的PC,并监测接受PC治疗患者的病情进展。