ACS Infect Dis. 2019 Feb 8;5(2):228-238. doi: 10.1021/acsinfecdis.8b00213. 

A Single-Step Gold Nanoparticle-Blood Serum Interaction Assay Reveals Humoral Immunity Development and Immune Status of Animals from Neonates to Adults.
 

Zheng T1, Crews J2, McGill JL3, Dhume K4, Finn C4, Strutt T4, McKinstry KK4, Huo Q1.
1 Department of Chemistry and NanoScience Technology Center , University of Central Florida , 12424 Research Parkway Suite 400 , Orlando , Florida 32826 , United States.
2 Warner University , 13896 Highway 27 , Lake Wales , Florida 33859 , United States.
3 Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine , Iowa State University , 1800 Christensen Drive , Ames , Iowa 50011-1134 , United States.
4 Burnett School of Biomedical Science, Division of Immunity and Pathogenesis, College of Medicine , University of Central Florida , 6900 Lake Nona Blvd. , Orlando , Florida 32827 , United States.

Abstract

A well-developed, functional immune system is paramount to combat harmful attacks from pathogenic organisms and prevent infectious diseases. Newborn animals and humans have only limited immunity upon birth, but their immune functions are expected to develop within weeks to months and eventually to reach a maturity that will provide full protection. Despite the importance of immune activity in animal and human health management, there is no convenient test available that allows for rapid assessment of the state of immune function in nonlaboratory settings. Here we report an extremely simple and rapid blood test that may be used in point-of-care clinics or field settings to evaluate the humoral immune status of animals. The test detects a cooperative interaction between a gold nanoparticle and arguably the three most important proteins involved in the immune system: immunoglobulin M (IgM), immunoglobulin G (IgG), and at least one complement protein, C3, in the blood serum. Such interactions cause the gold nanoparticles to form clusters and aggregates. The average particle size of the gold nanoparticle-serum mixture, measured by dynamic light scattering, corresponds positively to the immune status and activity of the subject. Our study demonstrates that the test may be used not only for monitoring the immune function development from neonates to adults, but also for detecting active immune responses during infection. Although data reported here are largely based on murine and bovine models, it is likely that this test will be applicable to humans as well.

KEYWORDS: gold nanoparticles; immune status; immunity development; infectious diseases; nanoparticle protein corona; virus infection

PMID: 30521752

 

Supplement:

A nanoparticle can be designed to mimic key properties of natural pathogens, like viruses. In this study, we demonstrated that one can use a gold nanoparticle as a universal pathogen substitute, or “ersatz” pathogen, to monitor the immunity and immune status of an animal. Many viruses have dimensions in the100 nm range, and we found that when a 100 nm gold nanoparticle (AuNP) is mixed with a blood serum, the interaction between the two mimics the humoral immune response in blood when a pathogen is present.

 

Because of the exceptionally strong light scattering property of gold nanoparticles, one can directly track the interaction between the gold nanoparticle and the blood serum using a particle sizing technique called dynamic light scattering. Using the assay protocol reported in our study, we have shown that this simple blood test can be used to monitor the immune function development of animals from neonates to adults, and detect immune responses during an active virus infection. The test is very easy to perform – it is a single reagent assay and it involves a single step of mixing a gold nanoparticle reagent solution with a blood serum sample. The test result is obtained within 15-20 min, and possibly shorter. The gold nanoparticle, in contrast to real pathogens, can be manufactured in large quantities and stored at ambient conditions for a long time.  Because of these attributes, this approach is ideally suited for deployment in the field outside of laboratory settings.

 

This new technology has broad potentials in diagnostics beyond infectious diseases. For example, autoimmune diseases and cancer cause well-documented and specific changes in immune factors that are detectable in serum samples. This extremely simple new blood test may thus be used a general screening test for early detection and diagnosis of infectious diseases, cancer, and many other medical conditions where active immune responses are involved.