Concept of thermal contrast for immunochromatographic lateral-flow assays. Laser heating and infrared detection of gold nanoparticles increase the visibility of the test-band signal at low analyte concentrations. Source: Qin et al., Angewandte Chemie International Edition (2012), Figure 1.
Combining 100-nm gold nanoparticles with a thermal contrast reader provides a 256-fold improvement in the sensitivity of CRP lateral-flow assays. Source: Zhan et al., Nano Letters (2017), Figure 4.
Our lab has developed a new technique entitled “Thermal Contrast” to increase the sensitivity of gold nanoparticle based diagnostics assays. With the importance of screening for diseases increasing, this technology introduces a thermal assay technique designed to outperform current methods in the detection of nanoparticles and other exogenous or endogenous particles within biological systems such as media, cells and tissues. By carefully studying the plasmonic heating of gold nanoparticles with laser irradiation, we have been able to show an order of magnitude improvement in sensitivity in detecting analytes in lateral flow assay strips when compared to visual inspection methods. This increased sensitivity can be tuned to compete with ELISA by careful selection of gold nanoparticle size and laser absorption. With those results, the necessity of more complicated lab procedures like latex agglutination and enzyme-linked immunosorbent assay methods may be reduced. Thermal contrast for lateral flow assays (LFA) cuts down on time and costs, increasing the value of this thermal assay technique which is now being commercialized by my start-up Vigilant Diagnostics.
Publications
Qin Z, Chan WCW, Boulware DR, Akkin T, Butler E, Bischof JC. Thermal Contrast of Lateral Flow Immunoassays Significantly Improves Analytical Sensitivity. Angewandte Chemie. 2012;51(18):4358–61. (The first demonstration of greatly enhanced sensitivity and semi-quantitation of lateral flow assays using laser irradiation. This is being commercialized).
Zhan L, Guo S, Song F, Gong Y, Xu F, Boulware DR, Chan WCW, McAlpine MC, and Bischof JC. The role of nanoparticle design in determining analytical performance of lateral flow immunoassays. Nano-Letters. 2017;17(12):7207-7212. (First demonstration that modified lateral flow assays with improved gold nanoparticle design can reach laboratory level (e.g. ELISA) sensitivity)
Liu Y, Zhan L, Qin Z, Sackrison J, Bischof JC. Perspective: Ultrasensitive and Highly Specific Lateral Flow Assays for Point-of-Care Diagnosis. ACS Nano. 2021:15(3);3593-3611 (Highly cited review of our work and others to show the direction of the lateral flow assay field towards laboratory level testing at the point of care).
Boulware D, Rolfes MA, Rajasingham R, von Hohenburg M, Qin Z, Shutz C, Kwizera R, Butler E, Bischof JC, Meya DB. Multisite Validation of Point-of-Care Cryptococcal Antigen Lateral Flow Assay and Novel Quantification by Laser Thermal Contrast Measurement. Emerg Infect Dis. 2014;20(1):45-53. (First demonstration of thermal contrast in a clinical cohort showing that thermal contrast correlates strongly with antigen burden measured by laboratory techniques).
Wang W, Qin Z, Boulware, DR, Pritt BS, Sloan LM, González IJ, Bell D, Rees-Channer R, Chiodini P, Chan WCW, Bischof JC. A Thermal Contrast Amplification Reader Yielding 8-fold Analytical Improvement for Disease Detection with Lateral Flow Assays. ACS Analy Chem. 2016;88(23):11774-82. (Demonstration in multiple commercially available lateral flow assays that thermal contrast yields almost an order of magnitude increase in sensitivity while producing a semi-quantitative result).
Wang Y, Louwagie E, Larkin D, Sankey S, Boulware DR, Bischof JC. Improved detection of group A: Streptococcus during thermal contrast amplification vs. visual reading of clinical rapid diagnostic tests. Analy Methods. 2019;11(15):2013-17. (Thermal contrast yields enhanced sensitivity and ability to detect 50% of false negatives in lateral flow assays from a clinical cohort of Strep patients).
Liu Y, Zhan L, Wang Y, Kangas J, Larkin D, Boulware DR, Bischof JC. Improved Influenza Diagnostics through Thermal Contrast Amplification. Diagnostics. 2021;11(3):462. (Demonstration of enhanced sensitivity in lateral flow assays from a clinical cohort of influenza patients).
Liu Y, Zhan L, Shen JW, Baro B, Alemany A, Sackrison J, Mitjà O, Bischof JC. fM–aM Detection of the SARS-CoV-2 Antigen by Advanced Lateral Flow Immunoassay Based on Gold Nanospheres. ACS App Nano Mat 2021:4(12);13826–13837 (Ability to make lateral flow assays that can reach both ELISA and PCR levels of sensitivity for COVID with thermal contrast enhancement).