[ { "id": "authors:cvqpm-g7q63", "collection": "authors", "collection_id": "cvqpm-g7q63", "cite_using_url": "https://authors.library.caltech.edu/records/cvqpm-g7q63", "type": "article", "title": "Hydrogel Encapsulation of a Designed Fluorescent Protein Biosensor for Continuous Measurements of Sub-100 nM Nicotine", "author": [ { "family_name": "Nichols", "given_name": "Aaron L.", "orcid": "0000-0001-9341-0049", "clpid": "Nichols-Aaron-L" }, { "family_name": "Marotta", "given_name": "Christopher B.", "orcid": "0000-0002-3110-0819", "clpid": "Marotta-Christopher-Bruno" }, { "family_name": "Friesenhahn", "given_name": "Nicholas J.", "orcid": "0000-0002-8129-0171", "clpid": "Friesenhahn-Nicholas-J" }, { "family_name": "Dalfonzo", "given_name": "Sophia R.", "clpid": "Dalfonzo-Sophia-R" }, { "family_name": "Muthusamy", "given_name": "Anand", "clpid": "Muthusamy-Anand" }, { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" }, { "family_name": "Mayo", "given_name": "Stephen L.", "orcid": "0000-0002-9785-5018", "clpid": "Mayo-S-L" }, { "family_name": "Dougherty", "given_name": "Dennis A.", "orcid": "0000-0003-1464-2461", "clpid": "Dougherty-D-A" }, { "family_name": "Lester", "given_name": "Henry A.", "orcid": "0000-0002-5470-5255", "clpid": "Lester-H-A" } ], "abstract": "
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The reinforcing, addictive, and therapeutic properties of nicotine depend strongly on the concentration and time dependence of nicotine in human biofluids. This pattern, termed [nicotine]t, varies markedly among methods of nicotine consumption and, for a given method, among individual users. Measuring [nicotine]t presents challenges: current approaches are expensive, invasive, tedious, and discontinuous. We report the entrapment of a purified, previously developed fluorescent biosensor protein, iNicSnFR12, in hydrogels. We optimized poly(ethylene glycol) diacrylate hydrogels for optical clarity and straightforward slicing. With fluorescence photometry of the hydrogels in a microscope or an integrated miniscope, [nicotine] is detected within a few min at the smoking- and vaping-relevant level of 10–100 nM (1.62–16.2 ng/mL), in a 250 μm thick hydrogel at the end of a 400 μm diameter multimode fiber optic. Concentration–response relationships are consistent with previous measurements of isolated iNicSnFR12. Leaching of iNicSnFR12 from the hydrogel and inactivation of iNicSnFR12 are minimal for several days, and reversible nicotine-induced fluorescence occurs at least 10 months after casting. This work provides the molecular, photophysical, and mechanical bases for minimally invasive, personal, wearable, continuous [nicotine] monitoring with straightforward extensions to existing, homologous “iDrugSnFR” proteins for other abused and prescribed drugs.

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", "doi": "10.1021/acsabm.5c01418", "issn": "2576-6422", "publisher": "American Chemical Society", "publication": "ACS Applied Bio Materials", "publication_date": "2026-01-19", "series_number": "2", "volume": "9", "issue": "2", "pages": "765-774" }, { "id": "authors:4c1m4-76298", "collection": "authors", "collection_id": "4c1m4-76298", "cite_using_url": "https://authors.library.caltech.edu/records/4c1m4-76298", "type": "monograph", "title": "Hydrogel encapsulation of a designed fluorescent protein biosensor for continuous measurements of sub-100 nanomolar nicotine", "author": [ { "family_name": "Nichols", "given_name": "Aaron L.", "orcid": "0000-0001-9341-0049", "clpid": "Nichols-Aaron-L" }, { "family_name": "Marotta", "given_name": "Christopher B.", "orcid": "0000-0002-3110-0819", "clpid": "Marotta-Christopher-Bruno" }, { "family_name": "Wagenaar", "given_name": "Daniel A.", "orcid": "0000-0002-6222-761X", "clpid": "Wagenaar-D-A" }, { "family_name": "Mayo", "given_name": "Stephen L.", "orcid": "0000-0002-9785-5018", "clpid": "Mayo-S-L" }, { "family_name": "Dougherty", "given_name": "Dennis A.", "orcid": "0000-0003-1464-2461", "clpid": "Dougherty-D-A" }, { "family_name": "Lester", "given_name": "Henry A.", "orcid": "0000-0002-5470-5255", "clpid": "Lester-H-A" } ], "abstract": "

The reinforcing and addictive properties of nicotine result from concentration- and time-dependent activation, desensitization, and upregulation of nicotinic acetylcholine receptors. However, time-resolved [nicotine] measurement in people who consume nicotine is challenging, as current approaches are expensive, invasive, tedious, and discontinuous. To address the challenge of continuous nicotine monitoring in human biofluids, we report the encapsulation of a purified, previously developed fluorescent biosensor protein, iNicSnFR12, into acrylamide hydrogels and polyethylene glycol diacrylate (PEGDA) hydrogels. We optimized the hydrogels for optical clarity and straightforward slicing. With fluorescence photometry of the hydrogels in a microscope and an integrated miniscope, [nicotine] is detected within a few min at the smoking- and vaping-relevant level of 10 - 100 nM (1.62 – 16.2 ng/ml), even in a 250 µm thick hydrogel at the end of 400 µm dia multimode fiber optic. Concentration-response relations are consistent with previous measurements on isolated iNicSnFR12. Leaching of iN-icSnFR12 from the hydrogel and inactivation of iNicSnFR12 are minimal for several days, and nicotine can be detected for at least 10 months after casting. This work provides the molecular, photophysical, and mechanical bases for personal, wearable continuous [nicotine] monitoring, with straightforward extensions to existing, homologous “iDrugSnFR” proteins for other abused and prescribed drugs.

", "doi": "10.1101/2024.12.02.625538", "publisher": "bioRxiv", "publication_date": "2024-12-02" } ]