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How to Choose the Right Nanoparticle for Your Lateral Flow Development
Lateral flow tests (LFA) are still on the way to revolutionize diagnostic industry, providing rapid and cost-effective solutions for a wide range of applications. As the demand for these tests continues to grow, so does the need for meticulous optimization and customization – especially for the topics
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Sensitivity,
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Selectivity,
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Sustainability.
In general, LFA rely on the detection of specific biomarkers or other analytes using nanoparticles that bind to them more or less specifically and produce a (visible) signal. Nanoparticles come in different types, sizes, shapes and coatings, and each one has its own advantages and disadvantages for LFA development. One crucial aspect of lateral flow test development lies in the selection of the appropriate nanoparticle. This plays a pivotal role for topics (1)-(3), and overall performance.
How can you choose the right nanoparticle for your LFA project?
In this article, we will delve shortly into the realm of nanoparticles and their significance in lateral flow tests. We will explore together the vast array of choices available and I hope to guide you in making informed decisions regarding your lateral flow development project. The basic research in this field is vast [1]. So this article is only like dipping the tip of your toes into the sea. We will explore this topic in future articles.
Gold nanoparticles, with their unique optical properties and broad commercial availability, have emerged, beside latex particles, as the most popular choice in lateral flow tests [2]. Their size, shape, and surface chemistry can be engineered, enabling enhanced assay performance [3]. However, gold is not the only option on the table. Other nanoparticles, such as quantum dots [4,5], carbon nanotubes [6,7], polymer nanoparticles [8,9], magnetic particles [10,11], silica nanoparticles [12], lipid-based nanoparticles [13] and upconversion nanoparticles [14,15] and hold considerable potential in overcoming specific challenges encountered in lateral flow test development [16,17].
One common misleading in LFA development is to choose the fanciest or latest nanoparticle for the assay, without considering its suitability for the specific application. While it may be tempting to use the latest and greatest nanoparticle technology, such as quantum dots [4,5], upconverting nanoparticles [14,15] or magnetic nanoparticles [10,11], these may not be the best choice for your LFA. Here are some reasons why [18]:
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Novel nanoparticles may have limited availability or high cost, which can affect the scalability and affordability of your LFA.
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Novel nanoparticles may have complex synthesis or functionalization methods, which can introduce variability and inconsistency in your LFA performance.
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Novel nanoparticles may have unknown or undesirable interactions with other components of your LFA, such as the sample matrix, the capture and detection antibodies, the nitrocellulose membrane or the conjugate pad.
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Novel nanoparticles may have regulatory or safety issues that can limit their use in certain markets or applications.
Therefore, instead of choosing the fanciest nanoparticle for your LFA development – especially in an industrial setting with commercialization in view - you should choose at least as a good starting point the best commercially available nanoparticle that meets your specific requirements. Here are some factors to consider when choosing a nanoparticle for your LFA [19]:
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Sensitivity: The nanoparticle should produce a strong and stable signal that can be easily detected by the naked eye or a suitable (of the shelf) reader device. The signal intensity depends on various factors like size, shape and optical properties of the nanoparticle, as well as its coating and conjugation efficiency. Generally, larger nanoparticles produce stronger signals than smaller ones, but they may also cause more background noise or aggregation or cannot be used in combination with your lateral flow membrane of choice [3].
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Specificity: The nanoparticle should bind selectively and specifically to your target biomarker, without cross-reacting with other substances in the sample. The specificity depends on the quality and affinity of the antibodies that are attached to the nanoparticle surface. You should choose a nanoparticle that has a suitable surface chemistry and functional groups that allow efficient and stable antibody conjugation. You should also optimize the antibody concentration and ratio to achieve optimal binding performance [20].
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Stability: The nanoparticle should maintain its signal and binding properties over time and under different storage and environmental conditions. The stability depends on the physical and chemical characteristics of the nanoparticle, as well as its coating and protection agents. You should choose a nanoparticle that has good resistance to oxidation, aggregation, degradation and leaching. You should also store and handle your nanoparticles properly to prevent decay or contamination [21].
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Compatibility: The nanoparticle should work well with other components of your LFA, such as the sample matrix, the capture and detection antibodies, and especially the nitrocellulose membrane or the conjugate pad. The compatibility depends on the interactions between the nanoparticle and these components, which can affect the flow rate, signal generation and background noise of your LFA. You should choose a nanoparticle that has minimal interference and nonspecific binding with these components. You should also test your nanoparticles in different sample types and matrices right from the start to evaluate their performance [22].
Gold nanoparticles are the most commonly used nanoparticles for LFAs because they have sufficiently high sensitivity and stability [21].
In conclusion, choosing the right nanoparticle for your LFA development is not a trivial task. You should not base your decision on novelty or popularity alone, but rather on suitability and functionality for your specific application. You should consider factors such as sensitivity, specificity, stability and compatibility when selecting a nanoparticle for your LFA project. You should also compare different types of nanoparticles and test them in various conditions to find the best one for your LFA. And you should definitely keep commercial availability and regulatory compliance in mind.
If you like to discuss this topic in more detail don’t hesitate to contact me and book a meeting.
References:
[1] Andreea-Cristina Mirica, Dana Stan; Ioana-Cristina Chelcea, Carmen Marinela Mihailescu, Augustin Ofiteru, Lorena-Andreea Bocancia-Mateescu (2022); "Latest Trends in Lateral Flow Immunoassay (LFIA) Detection Labels and Conjugation Process"; FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY.
[2] Ardekani LS, Thulstrup PW (2022); "Gold Nanoparticle-Mediated Lateral Flow Assays for Detection of Host Antibodies and COVID-19 Proteins"; Nanomaterials.
[3] V Borse, AN Konwar (2020); “Synthesis and characterization of gold nanoparticles as a sensing tool for the lateral flow immunoassay development”; Sensors International.
[4] W Chen; H Chen; Y Liu; H Wei; Y Wang; Z Rong; X Liu (2022); "An Integrated Fluorescent Lateral Flow Assay for Multiplex Point-of-care Detection of Four Respiratory Viruses", ANALYTICAL BIOCHEMISTRY.
[5] X Zhong; Q Fu; Y Wang; L Long; W Jiang; M Chen; H Xia; P Zhang; F Tan (2023); "CRISPR-based Quantum Dot Nanobead Lateral Flow Assay for Facile Detection of Varicella-zoster Virus", APPLIED MICROBIOLOGY AND BIOTECHNOLOGY.
[6] C Deng; H Li; S Qian; P Fu; H Zhou; J Zheng; Y Wang (2022); "An Emerging Fluorescent Carbon Nanobead Label Probe for Lateral Flow Assays and Highly Sensitive Screening of Foodborne Toxins and Pathogenic Bacteria", ANALYTICAL CHEMISTRY.
[7] L Willemsen; J Wichers; M Xu; R Van Hoof; C Van Dooremalen; A Van Amerongen; J Peters (2022); "Biosensing Chlorpyrifos in Environmental Water Samples By A Newly Developed Carbon Nanoparticle-Based Indirect Lateral Flow Assay", BIOSENSORS.
[8] SE Seo; E Ryu; J Kim; CJ Shin; OS Kwon (2023); "Fluorophore-encapsulated Nanobeads for On-site, Rapid, and Sensitive Lateral Flow Assay", SENSORS AND ACTUATORS. B, CHEMICAL.
[9] X Hu; J Liao; H Shan; H He; Z Du; M Guan; J Hu; J Li; B Gu (2023); "A Novel Carboxyl Polymer-modified Upconversion Luminescent Nanoprobe for Detection of Prostate-specific Antigen in The Clinical Gray Zonebase By Flow Immunoassay Strip", METHODS.
[10] M Salvador; JL Marqués-Fernández; A Bunge; JC Martínez-García; R Turcu; D Peddis; M Del Mar García-Suárez; MD Cima-Cabal; M Rivas (2022); "Magnetic Nanoclusters Increase The Sensitivity of Lateral Flow Immunoassays for Protein Detection: Application to Pneumolysin As A Biomarker for Streptococcus Pneumoniae", NANOMATERIALS.
[11] A Moyano; M Salvador; JC Martínez-García; V Socoliuc; L Vékás; D Peddis; MA Alvarez; M Fernández; M Rivas; MC Blanco-López (2019); "Magnetic Immunochromatographic Test For Histamine Detection In Wine", ANALYTICAL AND BIOANALYTICAL CHEMISTRY.
[12] Q Yu, HD Trinh, Y Lee, T Kang, L Chen, S Yoon, J Choo (2023), "SERS-ELISA using silica-encapsulated Au core-satellite nanotags for sensitive detection of SARS-CoV-2", Sens Actuators B Chem.
[13] S Rink, B. Kaise., MS Steiner. et al (2022), "Highly sensitive interleukin 6 detection by employing commercially ready liposomes in an LFA format.", Anal Bioanal Chem.
[14] JC Brandmeier, N Jurga, T Grzyb, A Hlaváček, R Obořilová, P Skládal, Z Farka, HH Gorris (2023). "Digital and Analog Detection of SARS-CoV-2 Nucleocapsid Protein via an Upconversion-Linked Immunosorbent Assay." Anal Chem.
[15] S Masoumeh Ghorbanpour, S Wen, TJ Kaitu'u-Lino, NJ Hannan, D Jin, L McClements (2023). "Quantitative Point of Care Tests for Timely Diagnosis of Early-Onset Preeclampsia with High Sensitivity and Specificity." Angew Chem Int Ed Engl.
[16] J Budd, BS Miller, NE Weckman, et al. (2023); „Lateral flow test engineering and lessons learned from COVID-19.”; Nat Rev Bioeng.
[17] A Sukumaran, T Thomas, R Thomas, RE Thomas, JK Paul, DM Vasudevan (2021); “Development and Troubleshooting in Lateral Flow Immunochromatography Assays.” Indian J Clin Biochem.
[18] H de Puig, I Bosch,L Gehrke, K Hamad-Schifferli (2017); „Challenges of the Nano-Bio Interface in Lateral Flow and Dipstick Immunoassays”. Trends Biotechnol.
[19] G Jiuchuan, S Chen, J Guo, X Ma (2021); „Nanomaterial Labels in Lateral Flow Immunoassays for Point-of-Care-Testing.” Journal of Materials Science & Technology.
[20] S Gao, JM. Guisán, J Rocha-Martin (2022); “Oriented immobilization of antibodies onto sensing platforms - A critical review”, Analytica Chimica Acta.
[21] W Hou, S Wang, X Wang, X Han, H Fan, et al. (2015); “Development of Colloidal Gold Immunochromatographic Strips for Detection of Riemerella anatipestifer.” PLOS ONE.
[22] S Singh, MR Hasan, A Jain, R Pilloton, J Narang (2023); “LFA: The Mysterious Paper-Based Biosensor: A Futuristic Overview”. Chemosensors.