Megan Muroski, PhD, senior product manager, life science business of Merck, shares how Gold nanoparticles continue to offer promise in diagnostic innovation.
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Gold nanoparticles, 3D illustration. Biotechnological and scientific background
Nanoparticles offer great promise for applications in biomedical research and clinical therapies. Nanoparticles, characterised as under 100nm in size, have unique physicochemical properties, including high surface area to volume ratio, strong signal intensities, and tuneable surface chemistries. Due to their large surface areas, nanomaterials can load a variety of molecules, such as antibodies, DNAs, and organic dyes, making them useful to detect low concentrations of analytes. They are also easily functionalised, allowing for multiple targets to be measured simultaneously.
The use of materials, such as iron oxide and gold, has been extensively explored for the field of nanomedicine as they offer desirable and unparalleled characteristics for chemical and biological detection methods. Gold nanoparticles are easy to synthesise, are commercially available, and considered biocompatible, which make them ideal reagents for use in many applications, including bioimaging, nanomedicine, and diagnostics. In addition, gold nanoparticles have a localised surface plasmon resonance that results in their characteristic ruby red colour, that can shift purple, depending on the size of the particle; this makes them particularly suitable for colourimetric readouts, such as lateral flow assays (LFAs). In addition, gold nanoparticles have excellent biocompatibility and stability which is crucial for diagnostic testing.
Due to the rise in demand for rapid testing during the COVID-19 pandemic, gold nanoparticles were catapulted into the mainstream of testing materials. The use of gold nanoparticle (GNP)-based lateral flow assays for detection of diseases like COVID-19 has demonstrated a fine balance of complexity and high sensitivity. In lateral flow development, the sensitivity of the reporter in the assay is dependent on the visual readout. There are many factors to consider during development, as reporters need to generate the largest possible signal, but also be small enough to travel through the membrane and bind to molecular targets. Other limitations of rapid testing include low sensitivity and cross-reactivity. Gold nanoparticles can overcome these limitations, as they can be made to be approximately the same size as antibodies, allowing for a 1:1 readout with a large signal with an easily visible testing line. Furthermore, gold nanoparticles can be easily modified, allowing for a host of applications based on their surface chemistry, such as the detection of the host antibody (serological) or antigen. Their suitability and stability provide additional value for often price-sensitive point-of-care diagnostics. Rapid testing diagnostics need to be inexpensive, easy to operate, and instrument-free.
The extensive research in gold nanoparticle lateral flow tests has resulted in significant improvements to their sensitivity, specificity, and overall performance. Despite the significant progress, further challenges remain for GNP-LFAs, including improving the reproducibility of gold nanoparticle synthesis and the lack of regulatory protocols for the development and characterisation of nanomaterials, which has limited mainstream integration of assays. This is a tremendously challenging task, as global regulations can vary, and the number of diverse nanomaterials is constantly expanding. However, it is important to understand, assess, and manage risks to ensure quality and regulatory standards are met. Companies, such as Merck, have developed the M-Clarity system to help industry researchers choose materials with the correct compliance to standards. Despite these challenges, gold nanoparticles are becoming increasingly commercially available with strict characterisation and quality controls. This may pave the way for a universal rapid testing solution that is readily available and accepted worldwide.