Non-Specific Gold Nanoparticle – Blood Serum Protein Interactions: Not Foe, but Powerful Tool for In Vitro Diagnostic Applications

Q. Huo
University of Central Florida,
United States

Keywords: gold, blood, biosensing, nanoparticles


Background: Gold nanoparticles have been studied extensively for potential applications in biosensing and in vitro diagnostics. However, despite more than four decades of intensive research, success has been limited. One of the most challenging bottleneck problems in this field is how to deal with the non-specific interactions between gold nanoparticles and a large number and quantity of serum proteins in blood samples. Target analyte proteins such as cancer biomarkers are typically found in the blood at very low concentrations ranging from pg/mL to ng/mL, while serum proteins including serum albumin and immunoglobins are present in the mg/mL range, which are millions to billions times higher than biomarker proteins. Under thermodynamic law, the non-specific interactions between gold nanoparticles and the abundant, non-target serum proteins are unavoidable. New Approach: In the last ten years, our laboratory has conducted extensive studies on the gold nanoparticle-blood serum protein interactions. Our research revealed that these so-called non-specific interactions are actually very specific biomarkers of the immune status and immune functions of the blood donors. Blood plasma contains all the biochemicals and molecules from the humoral immune system. When a gold nanoparticle is mixed with a blood plasma or serum sample in vitro, immune-related proteins, especially immunoglobins and complement proteins, will interact with the gold nanoparticle as if it is a pathogen. The interaction product, which can be quantitatively measured by monitoring the optical property change of the gold nanoparticles, is indicative of the immune status of the blood sample donor. Immune responses and immune status change are involved in almost all infectious diseases and certain types of cancer. The detection of immune status change can serve as a diagnostic tool for the detection and diagnosis of these diseases. Results: In this talk, I will discuss our most recent work of using this test to detect the immune responses to COVID-19 infection. It is well noticed that upon infection with COVID-19, most people will develop no or mild symptoms, but a small percentage of the population will progress into severe symptoms that may eventually lead to death. Our study revealed that patients who developed moderate to severe symptoms had very different immune responses than those who did not. The nanoparticle test we developed could be potentially used to identify COVID-19 patients who are at increased clinical risk versus those with low risk for more effective patient treatment and management. Conclusion: The non-specific interactions between nanoparticles and blood serum proteins, once considered as a foe for in vitro diagnostic test development, can be used as valuable biomarkers to study and monitor the immune status and immune activity associated with various diseases. New blood tests may be developed out of these interactions for clinical and diagnostic applications.