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Until now, automation in nanomaterial research has been largely focused on the automated synthesis of engineered nanoparticles (NPs) including the screening of synthesis parameters and the automation of characterization methods such as electron microscopy. Despite the rapidly increasing number of NP samples analyzed due to increasing requirements on NP quality control, increasing safety concerns, and regulatory requirements, automation has not yet been introduced into workflows of analytical methods utilized for screening, monitoring, and quantifying functional groups (FGs) on NPs. To address this gap, we studied the potential of simple automation tools for the quantification of amino surface groups on different types of aminated NPs, varying in size, chemical composition, and optical properties, with the exemplarily chosen sensitive optical fluorescamine (Fluram) assay. This broadly applied, but reportedly error-prone assay, which utilizes a chromogenic reporter, involves multiple pipetting and dilution steps and photometric or fluorometric detection. In this study, we compared the influence of automated and manual pipetting on the results of this assay, which was automatically read out with a microplate reader. Special emphasis was dedicated to parameters like accuracy, consistency, achievable uncertainties, and speed of analysis and to possible interferences from the NPs. Our results highlight the advantages of automated surface FG quantification and the huge potential of automation for nanotechnology. In the future, this will facilitate process and quality control of NP fabrication, surface modification, and stability monitoring and help to produce large data sets for nanomaterial grouping approaches for sustainable and safe-by-design, performance, and risk assessment studies.
Dai, W. G.; Pollock-Dove, C.; Dong, L. C.; Li, S. Advanced screening assays to rapidly identify solubility-enhancing formulations: High-throughput, miniaturization and automation. Adv. Drug Deliv. Rev. 2008, 60, 657–672.
Ahene, A. B.; Morrow, C.; Rusnak, D.; Spitz, S.; Usansky, J.; Pils, H.; Civoli, F.; Pandya, K.; Sue, B.; Leach, D. et al. Ligand binding assays in the 21st century laboratory: Automation. AAPS J. 2012, 14, 142–153.
Ray, C. A.; Ahene, A. B. Ligand binding assays in the 21st century laboratory-a call for change. AAPS J. 2012, 14, 377–379.
Fang, X. N.; Zheng, Y. Z.; Duan, Y. K.; Liu, Y.; Zhong, W. W. Recent advances in design of fluorescence-based assays for high-throughput screening. Anal. Chem. 2019, 91, 482–504.
Hecko, S.; Schiefer, A.; Badenhorst, C. P. S.; Fink, M. J.; Mihovilovic, M. D.; Bornscheuer, U. T.; Rudroff, F. Enlightening the path to protein engineering: Chemoselective turn-on probes for high-throughput screening of enzymatic activity. Chem. Rev. 2023, 123, 2832–2901.
Hess, J. F.; Kohl, T. A.; Kotrová, M.; Rönsch, K.; Paprotka, T.; Mohr, V.; Hutzenlaub, T.; Brüggemann, M.; Zengerle, R.; Niemann, S. et al. Library preparation for next generation sequencing: A review of automation strategies. Biotechnol. Adv. 2020, 41, 107537.
Holland, I.; Davies, J. A. Automation in the life science research laboratory. Front. Bioeng. Biotechnol. 2020, 8, 571777.
Christensen, M.; Yunker, L. P. E.; Shiri, P.; Zepel, T.; Prieto, P. L.; Grunert, S.; Bork, F.; Hein, J. E. Automation isn't automatic. Chem. Sci. 2021, 12, 15473–15490.
Abolhasani, M.; Kumacheva, E. The rise of self-driving labs in chemical and materials sciences. Nat. Synth. 2023, 2, 483–492.
Taguchi, S.; Suda, Y.; Irie, K.; Ozaki, H. Automation of yeast spot assays using an affordable liquid handling robot. SLAS Technol. 2023, 28, 55–62.
Manzano, J. S.; Hou, W. D.; Zalesskiy, S. S.; Frei, P.; Wang, H.; Kitson, P. J.; Cronin, L. An autonomous portable platform for universal chemical synthesis. Nat. Chem. 2022, 14, 1311–1318.
Li, Y. C.; Xia, L. L.; Fan, Y. M.; Wang, Q. Y.; Hu, M. Recent advances in autonomous synthesis of materials. ChemPhysMater 2022, 1, 77–85.
Dembski, S.; Schwarz, T.; Oppmann, M.; Bandesha, S. T.; Schmid, J.; Wenderoth, S.; Mandel, K.; Hansmann, J. Establishing and testing a robot-based platform to enable the automated production of nanoparticles in a flexible and modular way. Sci. Rep. 2023, 13, 11440.
Xing, C. Y.; Chen, G. Y.; Zhu, X.; An, J. K.; Bao, J. C.; Wang, X.; Zhou, X. Q.; Du, X. L.; Xu, X. X. Synthesis of carbon dots with predictable photoluminescence by the aid of machine learning. Nano Res. 2024, 17, 1984–1989.
Rietscher, R.; Thum, C.; Lehr, C. M.; Schneider, M. Semi-automated nanoprecipitation-system-an option for operator independent, scalable and size adjustable nanoparticle synthesis. Pharm. Res. 2015, 32, 1859–1863.
Epps, R. W.; Bowen, M. S.; Volk, A. A.; Abdel-Latif, K.; Han, S. Y.; Reyes, K. G.; Amassian, A.; Abolhasani, M. Artificial chemist: An autonomous quantum dot synthesis bot. Adv. Mater. 2020, 32, 2001626.
Salley, D.; Keenan, G.; Grizou, J.; Sharma, A.; Martín, S.; Cronin, L. A nanomaterials discovery robot for the Darwinian evolution of shape programmable gold nanoparticles. Nat. Commun. 2020, 11, 2771.
Chan, E. M. Combinatorial approaches for developing upconverting nanomaterials: High-throughput screening, modeling, and applications. Chem. Soc. Rev. 2015, 44, 1653–1679.
Lüdicke, M. G.; Hildebrandt, J.; Schindler, C.; Sperling, R. A.; Maskos, M. Automated quantum dots purification via solid phase extraction. Nanomaterials 2022, 12, 1983.
Xia, X. J.; Sivonxay, E.; Helms, B. A.; Blau, S. M.; Chan, E. M. Accelerating the design of multishell upconverting nanoparticles through Bayesian optimization. Nano Lett. 2023, 23, 11129–11136.
Salaheldin, A. M.; Walter, J.; Herre, P.; Levchuk, I.; Jabbari, Y.; Kolle, J. M.; Brabec, C. J.; Peukert, W.; Segets, D. Automated synthesis of quantum dot nanocrystals by hot injection: Mixing induced self-focusing. Chem. Eng. J. 2017, 320, 232–243.
Jiang, Y. B.; Salley, D.; Sharma, A.; Keenan, G.; Mullin, M.; Cronin, L. An artificial intelligence enabled chemical synthesis robot for exploration and optimization of nanomaterials. Sci. Adv. 2022, 8, eabo2626.
Murthy, C. R.; Gao, B.; Tao, A. R.; Arya, G. Automated quantitative image analysis of nanoparticle assembly. Nanoscale 2015, 7, 9793–9805.
Wang, X.; Zeng, Q.; Xie, F.; Wang, J. A.; Yang, Y. T.; Xu, Y.; Li, J. H.; Yu, H. Automated nanoparticle analysis in surface plasmon resonance microscopy. Anal. Chem. 2021, 93, 7399–7404.
Geißler, D.; Wegmann, M.; Jochum, T.; Somma, V.; Sowa, M.; Scholz, J.; Fröhlich, E.; Hoffmann, K.; Niehaus, J.; Roggenbuck, D. et al. An automatable platform for genotoxicity testing of nanomaterials based on the fluorometric γ-H2AX assay reveals no genotoxicity of properly surface-shielded cadmium-based quantum dots. Nanoscale 2019, 11, 13458–13468.
Egbuna, C.; Parmar, V. K.; Jeevanandam, J.; Ezzat, S. M.; Patrick-Iwuanyanwu, K. C.; Adetunji, C. O.; Khan, J.; Onyeike, E. N.; Uche, C. Z.; Akram, M. et al. Toxicity of nanoparticles in biomedical application: Nanotoxicology. J. Toxicol. 2021, 2021, 9954443.
Kim, S. T.; Saha, K.; Kim, C.; Rotello, V. M. The role of surface functionality in determining nanoparticle cytotoxicity. Acc. Chem. Res. 2013, 46, 681–691.
Jeliazkova, N.; Bleeker, E.; Cross, R.; Haase, A.; Janer, G.; Peijnenburg, W.; Pink, M.; Rauscher, H.; Svendsen, C.; Tsiliki, G. et al. How can we justify grouping of nanoforms for hazard assessment? Concepts and tools to quantify similarity. NanoImpact 2022, 25, 100366.
Kunc, F.; Nirmalananthan-Budau, N.; Rühle, B.; Sun, Y.; Johnston, L. J.; Resch-Genger, U. Interlaboratory comparison on the quantification of total and accessible amine groups on silica nanoparticles with qNMR and optical assays. Anal. Chem. 2021, 93, 15271–15278.
Geißler, D.; Nirmalananthan-Budau, N.; Scholtz, L.; Tavernaro, I.; Resch-Genger, U. Analyzing the surface of functional nanomaterials-how to quantify the total and derivatizable number of functional groups and ligands. Microchim. Acta 2021, 188, 321.
Quevedo, P. D.; Behnke, T.; Resch-Genger, U. Streptavidin conjugation and quantification-a method evaluation for nanoparticles. Anal. Bioanal. Chem. 2016, 408, 4133–4149.
Chatterjee, K.; Sarkar, S.; Jagajjanani Rao, K.; Paria, S. Core/shell nanoparticles in biomedical applications. Adv. Colloid Interface Sci. 2014, 209, 8–39.
Pallavi, P.; Harini, K.; Alshehri, S.; Ghoneim, M. M.; Alshlowi, A.; Gowtham, P.; Girigoswami, K.; Shakeel, F.; Girigoswami, A. From synthetic route of silica nanoparticles to theranostic applications. Processes 2022, 10, 2595.
Spoială, A.; Ilie, C. I.; Crăciun, L. N.; Ficai, D.; Ficai, A.; Andronescu, E. Magnetite-silica core/shell nanostructures: From surface functionalization towards biomedical applications-a review. Appl. Sci. 2021, 11, 11075.
Borse, S.; Rafique, R.; Murthy, Z. V. P.; Park, T. J.; Kailasa, S. K. Applications of upconversion nanoparticles in analytical and biomedical sciences: A review. Analyst 2022, 147, 3155–3179.
Felbeck, T.; Hoffmann, K.; Lezhnina, M. M.; Kynast, U. H.; Resch-Genger, U. Fluorescent nanoclays: Covalent functionalization with amine reactive dyes from different fluorophore classes and surface group quantification. J. Phys. Chem. C 2015, 119, 12978–12987.
Moser, M.; Nirmalananthan, N.; Behnke, T.; Geißler, D.; Resch-Genger, U. Multimodal cleavable reporters versus conventional labels for optical quantification of accessible amino and carboxy groups on nano- and microparticles. Anal. Chem. 2018, 90, 5887–5895.
Chen, Y.; Zhang, Y. Q. Fluorescent quantification of amino groups on silica nanoparticle surfaces. Anal. Bioanal. Chem. 2011, 399, 2503–2509.
Hsiao, I. L.; Fritsch-Decker, S.; Leidner, A.; Al-Rawi, M.; Hug, V.; Diabaté, S.; Grage, S. L.; Meffert, M.; Stoeger, T.; Gerthsen, D. et al. Biocompatibility of amine-functionalized silica nanoparticles: The role of surface coverage. Small 2019, 15, 1805400.
Derayea, S. M.; Samir, E. A review on the use of fluorescamine as versatile and convenient analytical probe. Microchem. J. 2020, 156, 104835.
Guan, X. L.; Chang, D. P. S.; Mok, Z. X.; Lee, B. Assessing variations in manual pipetting: An under-investigated requirement of good laboratory practice. J. Mass Spectrom. Adv. Clin. Lab 2023, 30, 25–29.
Pandya, K.; Ray, C. A.; Brunner, L.; Wang, J.; Lee, J. W.; DeSilva, B. Strategies to minimize variability and bias associated with manual pipetting in ligand binding assays to assure data quality of protein therapeutic quantification. J. Pharm. Biomed. Anal. 2010, 53, 623–630.
Lippi, G.; Lima-Oliveira, G.; Brocco, G.; Bassi, A.; Salvagno, G. L. Estimating the intra- and inter-individual imprecision of manual pipetting. Clin. Chem. Lab. Med. 2017, 55, 962–966.
Schmidt, S.; Tavernaro, I.; Cavelius, C.; Weber, E.; Kümper, A.; Schmitz, C.; Fleddermann, J.; Kraegeloh, A. Silica nanoparticles for intracellular protein delivery: A novel synthesis approach using green fluorescent protein. Nanoscale Res. Lett. 2017, 12, 545.
Ding, H. L.; Zhang, Y. X.; Wang, S.; Xu, J. M.; Xu, S. C.; Li, G. H. Fe3O4@SiO2 core/shell nanoparticles: The silica coating regulations with a single core for different core sizes and shell thicknesses. Chem. Mater. 2012, 24, 4572–4580.
Roebben, G.; Kestens, V.; Varga, Z.; Charoud-Got, J.; Ramaye, Y.; Gollwitzer, C.; Bartczak, D.; Geißler, D.; Noble, J.; Mazoua, S. et al. Reference materials and representative test materials to develop nanoparticle characterization methods: The NanoChOp project case. Front. Chem. 2015, 3, 56.
Dietrich, P. M.; Streeck, C.; Glamsch, S.; Ehlert, C.; Lippitz, A.; Nutsch, A.; Kulak, N.; Beckhoff, B.; Unger, W. E. S. Quantification of silane molecules on oxidized silicon: Are there options for a traceable and absolute determination. Anal. Chem. 2015, 87, 10117–10124.
Sun, Y.; Kunc, F.; Balhara, V.; Coleman, B.; Kodra, O.; Raza, M.; Chen, M. H.; Brinkmann, A.; Lopinski, G. P.; Johnston, L. J. Quantification of amine functional groups on silica nanoparticles: A multi-method approach. Nanoscale Adv. 2019, 1, 1598–1607.
Ashby, J.; Duan, Y. K.; Ligans, E.; Tamsi, M.; Zhong, W. W. High-throughput profiling of nanoparticle-protein interactions by fluorescamine labeling. Anal. Chem. 2015, 87, 2213–2219.
Murugayah, S. A.; Warring, S. L.; Gerth, M. L. Optimisation of a high-throughput fluorescamine assay for detection of N-acyl-L-homoserine lactone acylase activity. Anal. Biochem. 2019, 566, 10–12.
Li, Z.; Xue, Z. W.; Wu, Z. S.; Han, J. H.; Han, S. F. Chromo-fluorogenic detection of aldehydes with a rhodamine based sensor featuring an intramolecular deoxylactam. Org. Biomol. Chem. 2011, 9, 7652–7654.
Ros-Lis, J. V.; Martínez-Máñez, R.; Soto, J. A selective chromogenic reagent for cyanide determination. Chem. Commun. 2002, 2248–2249
Li, X. H.; Gao, X. H.; Shi, W.; Ma, H. M. Design strategies for water-soluble small molecular chromogenic and fluorogenic probes. Chem. Rev. 2014, 114, 590–659.
Hennig, A.; Borcherding, H.; Jaeger, C.; Hatami, S.; Würth, C.; Hoffmann, A.; Hoffmann, K.; Thiele, T.; Schedler, U.; Resch-Genger, U. Scope and limitations of surface functional group quantification methods: Exploratory study with poly(acrylic acid)-grafted micro- and nanoparticles. J. Am. Chem. Soc. 2012, 134, 8268–8276.