Nano-bio-chips for high performance multiplexed protein detection: Determinations of cancer biomarkers in serum and saliva using quantum dot bioconjugate labels

Abstract

The integration of semiconductor nanoparticle quantum dots (QDs) into a modular, microfluidic biosensor for the multiplexed quantitation of three important cancer markers, carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), and Her-2/Neu (C-erbB-2) was achieved. The functionality of the integrated sample processing, analyte capture and detection modalities was demonstrated using both serum and whole saliva specimens. Here, nano-bio-chips that employed a fluorescence transduction signal with QD-labeled detecting antibody were used in combination with antigen capture by a microporous agarose bead array supported within a microfluidics ensemble so as to complete the sandwich-type immunoassay. The utilization of QD probes in this miniaturized biosensor format resulted in signal amplification 30 times relative to that of standard molecular fluorophores as well as affording a reduction in observed limits of detection by nearly 2 orders of magnitude (0.02 ng/mL CEA; 0.11 pM CEA) relative to enzyme-linked immunosorbent assay (ELISA). Assay validation studies indicate that measurements by the nano-bio-chip system correlate to standard methods at R 2 = 0.94 and R 2 = 0.95 for saliva and serum, respectively. This integrated nano-bio-chip assay system, in tandem with next-generation fluorophores, promises to be a sensitive, multiplexed tool for important diagnostic and prognostic applications.

The potential legacy of cancer nanotechnology: cellular selection

“…One such advanced example are 'Nanobiochips' that have been developed as integrated biosensors using quantum dots (QDs) that can potentially be used as multiplexed tools for quantitation of cancer markers such as carcinoembryonic antigen (CEA), cancer antigen (CA) 125, and Her-2/Neu (C-erbB-2). They offer very high specificity in serum and saliva and may also be integrated with nanofluidic arrays to facilitate detection of sub cellular constituents [15,16] …”

Detection of Cancer Biomarkers With Nanotechnology

“…The integration of fluorescent QDs into a microfluidic biosensor for the multiplexed quantification of CEA, CA 125 and Her2/neu was studied (Jokerst et al, 2009). The utilization of QD probes significantly contributed to the signal amplification and the decrease of the DL.…”

Programmable Bio-NanoChip Technology for the Diagnosis of Cardiovascular Disease at the Point of Care

“…toward this goal, we have worked to improve the current state of PoC ivd through the development, validation, and implementation of P-BnCs ( Figure 1a). [17][18][19][20][21][22][23][24] the "programmability" feature of the system refers to the capacity of the sensor ensemble to function as a standard platform that can be reprogrammed to serve a new application by inserting a molecular-level code (i.e., the biomarker-specific reagents). the "bio" terminology refers to the capacity to measure and extract the bio-signatures associated with the disease progression.…”