{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:48:27Z","timestamp":1790488107979,"version":"4.1.0"},"reference-count":24,"publisher":"American Chemical Society (ACS)","issue":"1","license":[{"start":{"date-parts":[[2017,12,22]],"date-time":"2017-12-22T00:00:00Z","timestamp":1513900800000},"content-version":"vor","delay-in-days":17,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_ccby_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35-GM119701"],"award-info":[{"award-number":["R35-GM119701"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000070","name":"National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"publisher","award":["R01-EB022592"],"award-info":[{"award-number":["R01-EB022592"]}],"id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000152","name":"Division of Molecular and Cellular Biosciences","doi-asserted-by":"publisher","award":["MCB-1254382"],"award-info":[{"award-number":["MCB-1254382"]}],"id":[{"id":"10.13039\/100000152","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1046289"],"award-info":[{"award-number":["OPP1046289"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,1,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Deficiencies in vitamins and minerals (micronutrients) are a critical global health concern, in part due to logistical difficulties in assessing population micronutrient status. Whole-cell biosensors offer a unique opportunity to address this issue, with the potential to move sample analysis from centralized, resource-intensive clinics to minimal-resource, on-site measurement. Here, we present a proof-of-concept whole-cell biosensor in Escherichia coli for detecting zinc, a micronutrient for which deficiencies are a significant public health burden. Importantly, the whole-cell biosensor produces readouts (pigments) that are visible to the naked eye, mitigating the need for measurement equipment and thus increasing feasibility for sensor field-friendliness and affordability at a global scale. Two zinc-responsive promoter\/transcription factor systems are used to differentially control production of three distinctly colored pigments in response to zinc levels in culture. We demonstrate strategies for tuning each zinc-responsive system to turn production of the different pigments on and off at different zinc levels, and we demonstrate production of three distinct color regimes over a concentration range relevant to human health. We also demonstrate the ability of the sensor cells to grow and produce pigment when cultured in human serum, the ultimate target matrix for assessing zinc nutritional status. Specifically, we present approaches to overcome innate immune responses that would otherwise hinder bacterial sensor survival, and we demonstrate production of multiple pigment regimes in human serum with different zinc levels. This work provides proof of principle for the development of low-cost, minimal-equipment, field-deployable biosensors for nutritional epidemiology applications.<\/jats:p>","DOI":"10.1021\/acssynbio.7b00292","type":"journal-article","created":{"date-parts":[[2017,12,5]],"date-time":"2017-12-05T00:08:20Z","timestamp":1512432500000},"page":"267-275","source":"Crossref","is-referenced-by-count":74,"title":["Development of a Pigment-Based Whole-Cell Zinc Biosensor\nfor Human Serum"],"prefix":"10.1021","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0872-8795","authenticated-orcid":true,"given":"Daniel M.","family":"Watstein","sequence":"first","affiliation":[{"name":"Georgia Institute of Technology , , 311 Ferst Drive NW , , ,","place":["Atlanta, Georgia, United States, 30332-0100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark P.","family":"Styczynski","sequence":"additional","affiliation":[{"name":"Georgia Institute of Technology , , 311 Ferst Drive NW , , ,","place":["Atlanta, Georgia, United States, 30332-0100"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2017,12,5]]},"reference":[{"key":"2026090116352230200_cit1","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/S0140-6736(07)61690-0","article-title":"Maternal and\nchild undernutrition: global and regional exposures and health consequences","volume":"371","author":"Black","year":"2008","journal-title":"Lancet"},{"key":"2026090116352230200_cit2","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.rsci.2016.05.005","article-title":"Proximate Composition, Mineral Content\nand Fatty Acids\nAnalyses of Aromatic and Non-Aromatic Indian Rice","volume":"24","author":"Verma","year":"2017","journal-title":"Rice Science"},{"key":"2026090116352230200_cit3","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/S0308-8146(02)00507-1","article-title":"Analysis of food composition data\non rice from a plant\ngenetic resources perspective","volume":"80","author":"Kennedy","year":"2003","journal-title":"Food Chem."},{"key":"2026090116352230200_cit4","doi-asserted-by":"publisher","first-page":"e50568","DOI":"10.1371\/journal.pone.0050568","article-title":"Estimating the Global\nPrevalence of Zinc Deficiency:\nResults Based on Zinc Availability in National Food Supplies and the\nPrevalence of Stunting","volume":"7","author":"Wessells","year":"2012","journal-title":"PLoS One"},{"key":"2026090116352230200_cit5","doi-asserted-by":"publisher","first-page":"0009","DOI":"10.1038\/s41551-016-0009","article-title":"Hand-powered ultralow-cost\npaper centrifuge","volume":"1","author":"Bhamla","year":"2017","journal-title":"Nature Biomedical Engineering"},{"key":"2026090116352230200_cit6","doi-asserted-by":"publisher","first-page":"2032","DOI":"10.1039\/b809830c","article-title":"Egg beater\nas centrifuge: isolating human blood plasma from whole blood in resource-poor\nsettings","volume":"8","author":"Wong","year":"2008","journal-title":"Lab Chip"},{"key":"2026090116352230200_cit7","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1039\/C1LC20803A","article-title":"Integrated\nseparation of blood plasma from whole blood for microfluidic paper-based\nanalytical devices","volume":"12","author":"Yang","year":"2012","journal-title":"Lab Chip"},{"key":"2026090116352230200_cit8","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/S0140-6736(13)60937-X","article-title":"Maternal and child\nundernutrition and overweight in low-income and middle-income countries","volume":"382","author":"Black","year":"2013","journal-title":"Lancet"},{"key":"2026090116352230200_cit9","first-page":"S94","article-title":"Assessment of the risk of zinc deficiency\nin populations and options\nfor its control","author":"Brown","year":"2004","journal-title":"Food Nutr. Bull. Suppl."},{"key":"2026090116352230200_cit10","doi-asserted-by":"publisher","first-page":"858S","DOI":"10.3945\/jn.115.220079","article-title":"Biomarkers of Nutrition\nfor Development\n(BOND)-Zinc Review","volume":"146","author":"King","year":"2016","journal-title":"J. Nutr."},{"issue":"28","key":"2026090116352230200_cit11","doi-asserted-by":"publisher","first-page":"S403","DOI":"10.1177\/15648265070283S303","article-title":"Use of serum zinc\nconcentration as an indicator of population zinc status","volume":"28","author":"Hess","year":"2007","journal-title":"Food Nutr. Bull."},{"key":"2026090116352230200_cit12","doi-asserted-by":"publisher","first-page":"37517","DOI":"10.1074\/jbc.274.53.37517","article-title":"DNA distortion mechanism\nfor transcriptional activation by ZntR, a Zn(II)-responsive MerR homologue\nin Escherichia coli","volume":"274","author":"Outten","year":"1999","journal-title":"J. Biol. Chem."},{"key":"2026090116352230200_cit13","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.ymben.2015.06.007","article-title":"Precise\nmetabolic engineering of\ncarotenoid biosynthesis in Escherichia coli towards a low-cost biosensor","volume":"31","author":"Watstein","year":"2015","journal-title":"Metab. Eng."},{"key":"2026090116352230200_cit14","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1046\/j.1365-2958.1999.01229.x","article-title":"ZntR is a Zn(II)-responsive\nMerR-like\ntranscriptional regulator of zntA in Escherichia coli","volume":"31","author":"Brocklehurst","year":"1999","journal-title":"Mol. Microbiol."},{"key":"2026090116352230200_cit15","doi-asserted-by":"publisher","first-page":"24321","DOI":"10.1074\/jbc.M001775200","article-title":"The zinc-responsive\nregulator Zur and its control of\nthe znu gene cluster encoding the ZnuABC zinc uptake system in Escherichia\ncoli","volume":"275","author":"Patzer","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2026090116352230200_cit16","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.ymben.2015.06.011","article-title":"Precision\nmetabolic engineering:\nThe design of responsive, selective, and controllable metabolic systems","volume":"31","author":"McNerney","year":"2015","journal-title":"Metab. 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Biochem."},{"key":"2026090116352230200_cit20","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1016\/j.molcel.2006.04.027","article-title":"Engineering\nControllable Protein\nDegradation","volume":"22","author":"McGinness","year":"2006","journal-title":"Mol. 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