Gold nanoparticle-based low limit of detection Love wave biosensor for carcinoembryonic antigens

Abstract

In this work, a Love wave biosensing platform is described for detecting cancer-related biomarker carcinoembryonic antigen (CEA). An ST 90°-X quartz Love wave device with a layer of SiO waveguide was combined with gold nanoparticles (Au NPs) to amplify the mass loading effect of the acoustic wave sensor to achieve a limit of detection of 37pg/mL. The strategy involves modifying the Au NPs with anti-CEA antibody conjugates to form nanoprobes in a sandwich immunoassay. The unamplified detection limit of the Love wave biosensor is 9.4ng/mL. This 2-3 order of magnitude reduction in the limit of detection brings the SAW platform into the range useful for clinical diagnosis. Measurement electronics and microfluidics are easily constructed for acoustic wave biosensors, such as the Love wave device described here, allowing for robust platforms for point of care applications for cancer biomarkers in general.

Finding the perfect match between nanoparticles and microfluidics to respond to cancer challenges

“…Among the approaches tested, different nanoparticles, such as quantum dots, gold and silver NP's, were modified with specific antibodies against different biomarkers known to be associated with cancer ( Figure 4). As shown in Table 1, [50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65] several studies have demonstrated different efficiencies regarding detection ranges of single or multiple biomarker detection.…”

“…In a very different approach, AuNPs were used to enhance the signal through the addition of mass (Figure 4, C). 57 In fact, in this example, the detection of proteins was obtained by a guided shear horizontal surface acoustic wave (SAW) biosensor, termed Love wave biosensor. This sensor is a piezoelectric mass sensor, which can detect small differences in mass on its surface, but at a higher sensitivity than other sensors, as for example quartz crystal microbalances.…”

Micro/Nano Technology for Next‐Generation Diagnostics

“…C) Love wave chip, PDMS microfluidic chip and schematic diagram of the complete sensor. Adapted with permission . Copyright 2017, Elsevier.…”

“…Bhethanabotla and co‐workers utilized a sandwich immunoassay with an additional AuNP signal amplification for the detection of cancer‐related biomarker, carcinoembryonic antigen (CEA). The AuNP amplification improved the LOD with 2–3 magnitude of order, resulting in a picogram‐level sensibility that covered the clinical detection range (Figure C) . Notably, for most reported biosensor researches, the types of sample were either artificial or serum in order to minimalize interferons from blood.…”

Design of a Portable Orthogonal Surface Acoustic Wave Sensor System for Simultaneous Sensing and Removal of Nonspecifically Bound Proteins

“…In applications demanding low limits of detection in the pg/mL range, such as for cancer biomarkers, enhancements using nanoscale physics is necessary to quantify these biomarker concentrations. One such example is given in our recent work using gold nanoprobes to construct an immunosensor for carcinoembryonic antigen (CEA) [11]. However, such a highly sensitive SAW biosensor is susceptible to background noise caused by the nonspecific adsorption of other proteins when used on a real sample such as a drop of blood.…”