Measurement of serum prostate cancer markers using a nanopore thin film based optofluidic chip

Abstract

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.

Nanomaterial-based biosensors for detection of prostate specific antigen

“…An improved detection limit of PSA (1 pg) was achieved by application of the optofluidic chip consisting of arrayed nanopore-based sensors fabricated from an anodic aluminum oxide thin film [144]. Such type of the biosensor capable of ultrasensitive determination of dual PCa biomarker (PSA and a neuroendocrine marker) was published for the first time showing 50–100-fold enhancement of sensitivity compared to traditional ELISA [144].…”

Rapid detection of theophylline using aptamer-based nanopore thin film sensor

“…More specifically, as shown in Fig.3, the optical interference fringes reflected from the sensor, the transducing signal of the sensor, result in shift before and after the theophylline is bound to the aptamer [10][11]. The sensor was fabricated using the process flow developed in our lab, described in detail in citation [9].…”

Modified ELISA for Ultrasensitive Diagnosis

“…The potential applications of this method depend on the specificity and strength of the antigen–antibody reaction being evaluated. Due to the limitation of ELISAs requiring the use of a purified antigen and an extraordinarily functional antibody, some researchers strongly propose that other methods be used, such as liquid chromatography–mass spectrometry (LC-MS) [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ] and various lab-on-a-chip methods [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. A recent trend in LC-MS development for diagnosis is to focus on the detection of drugs and biomarkers, including peptides and steroids, owing to difficulties in preparing suitable antibodies against these small molecules, whereas lab-on-a-chip–based platforms are thought to offer easier sample preparation, chemical manipulation and reaction, and high throughput using various novel detection techniques with, sometimes, label-free detection.…”