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. 2012 Apr 27;51(18):4358-61.
doi: 10.1002/anie.201200997. Epub 2012 Mar 23.

Significantly improved analytical sensitivity of lateral flow immunoassays by using thermal contrast

Zhenpeng Qin  1 , Warren C W Chan, David R Boulware, Taner Akkin, Elissa K Butler, John C Bischof
Affiliations

Significantly improved analytical sensitivity of lateral flow immunoassays by using thermal contrast

Zhenpeng Qin et al. Angew Chem Int Ed Engl. .
No abstract available

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Figures

Figure 1
Figure 1
Concept of thermal contrast for immunochromatographic lateral flow assays (LFAs). Monoclonal antibodies conjugated to gold nanoparticles (GNP) bind the target analyte. This GNP-antibody-antigen complex binds with monoclonal antibodies attached to the dipstick substrate, retaining the GNP in the test region and leading to visible color change (visual contrast) at the test band. Under low antigen conditions when there are insufficient bound GNPs for visual contrast, thermal contrast can detect the presence of GNPs in the test band (inset), with low-cost LED and infrared temp gun available over-the-counter. The control band ensures the success of the assay.
Figure 2
Figure 2
Thermal contrast enhances the detection of gold nanoparticle (GNP) solution. (A) Examples of visual and thermal images of GNP solution and pure water.(B) Experimental demonstration showing 100-fold increase in the limit of detection with a CW laser (0.5W, 532nm wavelength). With higher laser power, lower concentrations of GNPs can be detected.
Figure 3
Figure 3
Thermal contrast enhances the detection of existing immunochromatographic lateral flow assays for cryptococcal antigen (CrAg). (A) Examples of visual and thermal images of dipsticks used for CrAg diagnosis. (B) Quantitative measurement of the thermal and visual detection of LFA at 2-fold serial dilutions. Thermal contrast (laser power 0.01W) shows extended dynamic range vs. visual contrast. The drop of signal at high concentrations is due to the high dose hook effect inherent with the LFA. The dashed line shows background from the control samples.
Figure 4
Figure 4
Strategies to improve thermal contrast by several orders of magnitude.(A) Thermal contrast can be improved by increasing the absorption per nanoparticle. Particle parameters: sphere D=30nm, nanorod D=12.7nm by L=49.5nm, and nanoshell Dcore = 120nm (silica), Dshell=150nm (gold). The thermal contrast (ΔTsignal) and nanoparticle concentrations are normalized. Inset shows the typical range of the absorption cross section per particle volume (Cabs/V) as calculated by Jain et al.[23]. The filled circles indicate the particular particles chosen for the plot. (B) Thermal contrast generated by different substrates with varying laser power (P). By reducing background absorption, this would: 1) increase the signal-to-noise ratio, and 2) allow the use of higher intensity laser excitation to increase the sensitivity and dynamic range of the thermal contrast measurement.
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