Progress 10/01/19 to 09/30/20
Outputs
Target Audience:Our target audience is broad. Our technology is provided to federal agencies including but not limited to NIH, USDA, EPA, USGS, and many state agencies as well as international organizations. The tools are used by farmers, pest control operators, and the agricultural chemical and agricultural biotechnological industries as well as foundations. There is also a community of companies that have developed around providing our technologies to end users. Changes/Problems:We anticipate no changes or major problems. Like in the early days of monoclonal antibodies in the 1970s years of work by many laboratories are critical before the new technology becomes well established internationally. Already it is clear that nanobody and other recombinant antibody and phage display technologies are far more cost effective and powerful than existing technology like monoclonal procedures. We will increasingly emphasize nanobody of VHH technology. However, like with realization of the potential of monoclonal technology it will take an international village collaborating in nanobody technology to accomplish the larger goals. Our research emphasis may change somewhat as new opportunities open and problems emerge. What opportunities for training and professional development has the project provided?This has been difficult during the pandemic, but we have maintained laboratory communication by zoom meetings and a 'WhatsApp' site for small group discussions. How have the results been disseminated to communities of interest?Our primary methods of discrimination have been through classical publications and scientific meetings What opportunities for training and professional development has the project provided? We have also provided direct instruction to tribes of the Yurok Nation in Northern California who want to use this technology to monitor contamination in the Klamath River Basin. What do you plan to do during the next reporting period to accomplish the goals?Since funding is not provided for these projects through the experiment station, we will continue to work hard to acquire funding from agencies such at the NIEHS, NINDS, Fulbright, NAS Egypt Project, collaborating Universities nationally and internationally and other groups. The funding will be used to continue and expand the work described above with special emphasis on practical applications of the nanobody technology in projects related to agriculture, health of agricultural workers and food safety. We just received notification from the National Academy of Sciences that we will be funded to look at field worker exposure to pesticides during the next year and we will submit this month a Program Project on the technology to NIEHS which has funded this work for 35 years.
Impacts
What was accomplished under these goals?
Our original goals were: Develop rapid methods for the detection of pesticides, mycotoxins, plant toxins, bioterrorism agents and other foreign compounds in the human food chain, the environment, as well as feed and forage. A. Develop and validate new immunoassays necessary to insure food safety and high environmental quality with an emphasis on compounds of interest to the agriculture. B. Further the used of recombinant technology and particularly the development of recombinant nanobody technology (VHH) for compounds in objective A. C. Advance immunochemical technology in general to develop field portable biosensor systems for point of care diagnostics to insure worker safety, agricultural product stewardship, environmental health and food safety. Our specific accomplishments are indicated in the 16 peer reviewed papers published this year. More broadly when we started environmental immunoassay work at UC in 1975 and published the first papers in the field. Our first pesticide immunoassay could monitor quantitatively a single isomer of an air, water and light unstable toxin with 8 optical and geometrical isomers. Now there now are over 21,000 peer reviewed publications with over 8000 in the last year. Through the years we have advanced the technology of antibody development being the first to develop monoclonal antibodies for pesticides, and now we have pioneered the use of recombinant nanobodies for environmental analysis and are approaching 200 publications in the field. This is one of the most exciting and revolutionary developments during my scientific life. We have trained scientists at UCD and around the world in its technology and our work has expanded to using these reagents not only for agriculture and environmental analysis but for things as remote as cancer biology. For immunoassay one needs the antibody but also signal transduction systems. These have involved the use of whole bacteria (E. coli) as the transduction system as well as possibly the most sensitive double sandwich ELISA based on nanobodies. We have found new polymeric enzyme reporter systems, employed a unique fluorescence resonance energy transfer system, a CuZnO electrochemical sensor, quantum dot nanobeads, chemoluminescence, lateral flow assays with smart phone analysis, for signal transduction and carbon nanotube fibers as solid supports.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Li D, Morisseau C, McReynolds CB, Duflot T, Bellien J, Nagra RM, Taha AY, Hammock BD. 2020. Development of Improved Double-Nanobody Sandwich ELISAs for Human Soluble Epoxide Hydrolase Detection in Peripheral Blood Mononuclear Cells of Diabetic Patients and the Prefrontal Cortex of Multiple Sclerosis Patients. Analytical Chemistry. 92(10):7334-7342. 10.1021/acs.analchem.0c01115. PMID: 32253910. IA [R35 ES030443, P42 ES04699]
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Riangrungroj P, Bever CS, Hammock BD, Polizzi KM. 2019. A label-free optical whole-cell
Escherichia coli biosensor for the detection of pyrethroid insecticide exposure. Scientific reports. 9(1):12466. 10.1038/s41598-019-48907-6. PMID: 31462650. PMCID: PMC6713742. [P42 ES04699] IA
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Sp�th J, Nording M, Lindberg R, Brodin T, Jansson S, Yang J, Wan D, Hammock B, Fick J. 2020. Novel metabolomic method to assess the effect-based removal efficiency of advanced wastewater treatment techniques. Environmental Chemistry. 17(1):1-5. https://doi.org/10.1071/EN19270. IA [R35 ES030443, P42 ES04699]
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Tang Z, Liu X, Su B, Chen Q, Cao H, Yun Y, Xu Y, Hammock BD. 2020. Ultrasensitive and rapid detection of ochratoxin A in agro-products by a nanobody-mediated FRET-based immunosensor. Journal of Hazardous Materials. 387:121678. https://doi.org/10.1016/j.jhazmat.2019.121678. IA [no grants listed]
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Ren W, Xu Y, Huang Z, Li Y, Tu Z, Zou L, He Q, Fu J, Liu S, Hammock BD. 2020. Single-chain variable fragment antibody-based immunochromatographic strip for rapid detection of fumonisin B1 in maize samples. Food Chemistry. 319:126546. https://doi.org/10.1016/j.foodchem.2020.126546. PMID: 32179370. IAA Bib. [P42 ES04699]
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Kumar S, Vasylieva N, Singh V, Hammock B, Singh SG. 2020. A Facile, Sensitive and Rapid Sensing Platform Based on CoZnO for Detection of Fipronil; an Environmental Toxin. Electroanalysis. 32(9):2056-2064. 10.1002/elan.202000051. IA. [R35 ES030443, P42 ES04699]
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Li P, Yang C, Liu B, Wu Q, Wang Y, Dong S, Zhang H, Vasylieva N, Hammock BD, Zhang C. 2020. Sensitive Immunochromatographic Assay Using Highly Luminescent Quantum Dot Nanobeads as Tracer for the Detection of Cyproheptadine Hydrochloride in Animal-Derived Food. Frontiers in Chemistry. 8(575). 10.3389/fchem.2020.00575. PMID:32760698. PMCID:PMC7372008. IA [R35 ES030443, P42 ES04699]
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Ren W, Li Z, Xu Y, Wan D, Barnych B, Li Y, Tu Z, He Q, Fu J, Hammock BD. 2019. One-Step Ultrasensitive Bioluminescent Enzyme Immunoassay Based on Nanobody/Nanoluciferase Fusion for Detection of Aflatoxin B(1) in Cereal. J Agric Food Chem. 67(18):5221-5229. 10.1021/acs.jafc.9b00688. PMID:30883117. PMCID: PMC7792509. IA [P42 ES04699]
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Li D, Cui Y, Morisseau C, Wagner KM, Cho YS, Hammock BD. 2020. Development of a Highly Sensitive Enzyme-Linked Immunosorbent Assay for Mouse Soluble Epoxide Hydrolase Detection by Combining a Polyclonal Capture Antibody with a Nanobody Tracer. Analytical Chemistry. 10.1021/acs.analchem.0c01511.
PMID:32786492. IA [R35 ES030443, P42 ES04699]
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Wang F, Li Z-F, Yang Y-Y, Wan D-B, Vasylieva N, Zhang Y-Q, Cai J, Wang H, Shen Y-D, Xu Z-L, Hammock BD. 2020. Chemiluminescent Enzyme Immunoassay and Bioluminescent Enzyme Immunoassay for Tenuazonic Acid Mycotoxin by Exploitation of Nanobody and NanobodyNanoluciferase Fusion. Analytical Chemistry. 92(17):11935-11942. 10.1021/acs.analchem.0c02338. PMID:32702970. IA [R35 ES030443, P42 ES04699]
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Li Z, Wang Y, Vasylieva N, Wan D, Yin Z, Dong J, Hammock BD. 2020. An Ultrasensitive Bioluminescent Enzyme Immunoassay Based on Nanobody/Nanoluciferase Heptamer Fusion for the Detection of Tetrabromobisphenol A in Sediment. Analytical Chemistry. 92(14):10083-10090. 10.1021/acs.analchem.0c01908. PMID:32559059. IA [R35ES030443, P42 ES04699]
- Type:
Journal Articles
Status:
Published
Year Published:
2021
Citation:
Li Z-F, Dong J-X, Vasylieva N, Cui Y-L, Wan D-B, Hua X-D, Huo J-Q, Yang D-C, Gee SJ, Hammock BD. 2021. Highly specific nanobody against herbicide 2,4-dichlorophenoxyacetic acid for monitoring of its contamination in environmental water. Science of The Total Environment. 753:141950. https://doi.org/10.1016/j.scitotenv.2020.141950. PMID:32906044. IA [R35ES030443, P42 ES04699]
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Hongsibsong S, Prapamontol T, Xu T, Hammock BD, Wang H, Chen Z-J, Xu Z-L. 2020. Monitoring of the Organophosphate Pesticide Chlorpyrifos in Vegetable Samples from Local Markets in Northern Thailand by Developed Immunoassay. Int J Environ Res Public Health. 17(13):4723. 10.3390/ijerph17134723. PMID: 32630084; PMCID: PMC7369984. [P42 ES04699] IA
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Tang Z, Mo F, Liu A, Duan S, Yang X, Liang L, Hou X, Yin S, Jiang X, Vasylieva N, Dong J, Barnych B, Hammock BD, Lu X. 2019. A Nanobody Against Cytotoxic T-Lymphocyte Associated Antigen-4 Increases the Anti-Tumor Effects of Specific CD8(+) T Cells. J Biomed Nanotechnol. 15(11):2229-2239. 10.1166/jbn.2019.2859. PMID 31847937. [R01DK107767] IA
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
El-Moghazy, Ahmed Y., Jingqian Huo, Noha Amaly, Natalia Vasylieva, Bruce D. Hammock, and Gang Sun. An Innovative Nanobody-Based Electrochemical Immunosensor Using Decorated Nylon Nanofibers for Point-of-Care Monitoring of Human Exposure to Pyrethroid Insecticides. ACS Applied Materials & Interfaces 12, no. 5 (2020): 6159-6168. DOI: 10.1021/acsami.9b16193. PMID: 31927905. PMCID: 7799635. IA
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Qi M, Huo J, Li Z, He C, Li D, Wang Y, Vasylieva N, Zhang J, Hammock BD. 2020. On-spot quantitative analysis of dicamba in field waters using a lateral flow immunochromatographic strip with smartphone imaging. Analytical and Bioanalytical Chemistry. 10.1007/s00216-020-02833-z. PMID:32737550. IA [P42 ES04699]
- Type:
Journal Articles
Status:
Published
Year Published:
2021
Citation:
Dong J, Li Z, Wang Y, Jin M, Shen Y, Xu Z, Abd El-Aty AM, Gee SJ, Hammock BD, Sun Y, Wang H. 2021. Generation of functional single-chain fragment variable from hybridoma and development of chemiluminescence enzyme immunoassay for determination of total malachite green in tilapia fish. Food Chemistry. 337:127780. https://doi.org/10.1016/j.foodchem.2020.127780. PMID:32799164. PMCID:PMC7541715. IA [P42 ES04699]
|
Progress 10/01/18 to 09/30/19
Outputs
Target Audience:The target audience includes regulatory agencies (in California, nationally and internationally), funding agencies, grower groups, the scientific community and others. Changes/Problems:We anticipate no changes or major problems. Like in the early days of monoclonal antibodies in the 1970s years of work by many laboratories are critical before the new technology becomes well established internationally. Already it is clear that nanobody and other recombinant antibody and phage display technologies are far more cost effective and powerful than existing technology. Our research emphasis may change somewhat as new opportunities open and problems emerge. What opportunities for training and professional development has the project provided?There are 30 scientists currently in the laboratory and of these 12 are involved in this project in addition to several undergraduate researchers. Thus providing training and professional development is an ongoing process. We have two weekly meetings where scientists both present and review research as part of this continuing professional development in addition to attendance at professional meetings. We provide training formally through several courses and notably our outreach at the NIEHS Superfund Meeting just held in Seattle. In addition to demonstrating our technologies we presented our work on pesticide contamination in Northern California resulting from cannabis culture. We worked closely with the Yurok Nation to present this work. The reagents are provided to laboratories around the world gratis and for example just this month we have run training programs in both China and in Egypt. How have the results been disseminated to communities of interest?This is in part covered above. In addition to peer reviewed publications, training of UCD and visiting scientists and students, international lectures and classes, and hosting a large national meeting in Sacramento, we have worked closely with the Yurok nation on exposure to pesticides associated with illegal cannabis culture. What do you plan to do during the next reporting period to accomplish the goals?Since funding is not provided for these projects through the experiment station we will continue to work hard to acquire funding from agencies such as the NIEHS, NINDS, Fulbright, NAS Egypt Project, collaborating Universities nationally and internationally and other groups. The funding will be used to continue and expand the work described above with special emphasis on practical applications of the nanobody technology in projects related to agriculture, health of agricultural workers and food safety.
Impacts
What was accomplished under these goals?
The accomplishments are clear from the 22 peer reviewed peer publications generated during this year, listed on Google and the laboratory website and below. Some of the publications are of particular note. We developed the first immunoassay for the insecticide fipronil and its toxic metabolite. This compound is widely used in field and row crop agriculture and in particular is used to treat external parasites of companion and domestic animals. The latter resulted in major contamination of the human food chain in Europe and our assay was well positioned for monitoring contaminated batches of food moving toward human consumption. From the basic standpoint this assay was based on a recombinant camel single-domain antibody fused with a reporter system. This recombinant nanobody illustrates a trend in the field of using these recombinant antibodies to replace monocolonal and polyclonal materials. This new technology leads to reduced cost, increased reproducibility, and improved performance. A recent use of this tecnhology was in monitoring endangered prairie dogs in a plague eradication project for fipronil. We developed a similar recombinant assay for neonicotinoid insecticides which along with fipronil is thought by some to be associated with honey bee decline. These assays facilitate monitoring of these pesticides in the field. We have also developed the first recombinant antibody to detect genetically engineered cereal crops with the Cry2A protein. We developed the first immunoassay for the potential terror weapon TETs which is far more sensitive the LC-MS and GLC-MS assays as well as able to be used by first responders in a terror attack. The assay has been valuable in pharmacokinetic studies to ask why TETs is so deadly and why finding antidotes has proven hard. As part of the NINDS Counteract program we have an antidote moving toward human trials. Such assays are of course critical for importing and exporting of recombinant crops. We of course continue to report poly and monoclonal antibody based assays and use all of these reagents to evaluate new reporter systems for improving sensitivity, reproducibility, field portability and other aspects of immunoassays. These improvements include optical, electrochemical, and other detection systems. We also are using these technologies to evaluate the use of nanobodies for human diagnosis and even treatment. For example we have developed nanobodies to the Pseudomonas virulence factor implicated in deaths of patients with cystic fibrosis, asthma and chronic obstructive pulmonary disorder. These are being evaluated both for diagnosis and treatment.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Hongsibsong S, Prapamontol T, Dong J-X, Bever CS, Xu Z-L, Gee SJ, Hammock BD. 2019. Exposure of consumers and farmers to organophosphate and synthetic pyrethroid insecticides in Northern Thailand. Journal of Consumer Protection and Food Safety. doi: 10.1007/s00003-019-01207-7.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Liu Z, Wang K, Wu S, Wang Z, Ding G, Hao X, Li QX, Li J, Gee SJ, Hammock BD, Xu T. 2019. Development of an immunoassay for the detection of carbaryl in cereals based on a camelid variable heavy-chain antibody domain. Journal of the Science of Food and Agriculture. Epub 2019/03/10. doi: 10.1002/jsfa.9672. PubMed PMID: 30851058.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Shu M, Xu Y, Dong J-x, Zhong C, Hammock BD, Wang W-j, Wu G-p. 2019. Development of a noncompetitive idiometric nanobodies phage immunoassay for the determination of fumonisin B1. Food and Agricultural Immunology 30(1):510-21. doi: 10.1080/09540105.2019.1604637.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Tang Z, Liu X, Wang Y, Chen Q, Hammock BD, Xu Y. 2019. Nanobody-based fluorescence resonance energy transfer immunoassay for noncompetitive and simultaneous detection of ochratoxin a and ochratoxin B. Environmental Pollution 251:238-45. doi: https://doi.org/10.1016/j.envpol.2019.04.135.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Huo J, Barnych B, Li Z, Wan D, Li D, Vasylieva N, Knezevic SZ, Osipitan OA, Scott JE, Zhang J, Hammock BD. 2019. Hapten Synthesis, Antibody Development, and a Highly Sensitive Indirect Competitive Chemiluminescent Enzyme Immunoassay for Detection of Dicamba. Journal of Agricultural and Food Chemistry. doi: 10.1021/acs.jafc.8b07134.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Mishra M, Tiwari S, Gunaseelan A, Li D, Hammock BD, Gomes AV. 2019. Improving the sensitivity of traditional Western blotting via Streptavidin containing Poly-horseradish peroxidase (PolyHRP). Electrophoresis. Epub 2019/04/26. doi: 10.1002/elps.201900059. PubMed PMID: 31021001.
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Cam M, Durieu E, Bodin M, Manousopoulou A, Koslowski S, Vasylieva N, Barnych B, Hammock BD, Bohl B, Koch P, Omori C, Yamamoto K, Hata S, Suzuki T, Karg F, Gizzi P, Erakovic Haber V, Bencetic Mihaljevic V, Tavcar B, Portelius E, Pannee J, Blennow K, Zetterberg H, Garbis SD, Auvray P, Gerber H, Fraering J, Fraering PC, Meijer L. 2018. Induction of Amyloid-beta42 Production by Fipronil and Other Pyrazole Inssecticides. J Alzheimers Dis. 62(4):1663-81. doi: 10.3233/jad-170875.
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Qiu Y, Li P, Dong S, Zhang X, Yang Q, Wang Y, Ge J, Hammock BD, Zhang C, Liu X. 2018. Phage-Mediated Competitive Chemiluminescent Immunoassay for Detecting Cry1Ab Toxin by Using an Anti-Idiotypic Camel Nanobody. J Agric Food Chem. 66(4):950-6. doi: 10.1021/acs.jafc.7b04923.
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Cui X, He Q, Shen D, Jiang Z, Chen Y, Zhao S, Hammock BD. 2018. Production and characteriation of a single-chain variable fragment-alkaline phosphatase fusion protein for glycocholic acid detection in a one-step enzyme-linked immunosorbent assay. Analytical Methods 10(22):2629-35. doi: 10.1039/C8AY00848E.
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
He J, Tian J, Xu J, Wang K, Li J, Gee SJ, Hammock BD, Li QX, Xu T. 2018. Strong and oriented conjugation of nanobodies onto magnetosomes for the development of a rapid immunomagnetic assay for the environmental detection of tetrabromobisphenol-A. Anal Bioanal Chem. 410(25):6633-42. doi: 10.1007/s00216-018-1270-9.
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Sun Z, Lv J Liu X, Tang Z, Wang X, Xu Y, Hammock BD. 2018. Development of a Nanobody-AviTag Fusion Protein and Its Application in a Streptavidin-Biotin-Amplified Enzyme-Linked Immunosorbent Assay for Ochratoxin A in Cereal. Anal Chem. 90(17):10628-34. doi: 10.1021/acs.analchem.8b03085.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Wang K, Vasylieva N, Wan D, Eads DA, Yang J, Tretten T, Barnych B, Li J, Li QX, Gee SJ, Hammock BD, Xu T. 2019. Quantitative Detection of Fipronil and Fipronil-Sulfone in Sera of Black-Tailed Prairie Dogs and Rats after Oral Exposure to Fipronil by Camel Single-Domain Antibody-Based Immunoassays. Anal Chem. 91(2):1532-40. doi: 10.1021/acs.analchem.8b04653.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Wang K, Liu Z, Ding G, Li J, Vasylieva N, Li QX, Li D, Gee SJ, Hammock BD, Xu T. 2019. Development of a one-step immunoassay for triazophos using camel single-domain antibody-alkaline phosphatase fusion protein. Anal Bioanal Chem. 411(6):1287-95. doi: 10.1007/s00216-018-01563-7.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Vasylieva N, Kitamura S, Dong J, Barnych B, Hvorecny KL, Madden DR, Gee SJ, Wolan DW, Morisseau C, Hammock BD. 2019. Nanobody-based binding assay for the discovery of potent inhibitors of CFTR inhibitory factor (Cif). Anal Chim Acta. 1057:106-13. doi: 10.1016/j.aca.2018.12.060. MCID: PMC6426448.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Mukhtar H, Ma L, Pang Q, Zhou Y, Wang X, Xu T, Hammock BD, Wang J. 2019. Cyclic peptide: a safe and effective alternative to synthetic aflatoxin B1-competitive antigens. Anal Bioanal Chem. doi: 10.1007/s00216-019-01862-7.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Ding Y, Hua X, Chen H, Gonzalez-Sapienza G, Barnych B, Liu F, Wang M, Hammock BD. 2019. A dual signal immunochromatographic strip for the detection of imidaclothiz using a recombinant fluorescent-peptide tracer and gold nanoparticles. Sensors and Actuators B: Chemcial. 297:126714. doi: https://doi.org/10.1016/j.snb.2019.26714.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Qiu Y, Li P, Liu B, Liu Y, Wang Y, Tao T, Xu J, Hammock BD, Liu X, Guan R, Zhang C. 2019. Phage-displayed nanobody based double antibody sandwich chemiluminescent immunoassay for the detection of Cry2A toxin in cereals. Food and Agricultural Immunology 30(1):924-936. doi: 10.1080/09540105.2019.1642307.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Wang Y, Li Z, Barnych B, Huo J, Wan D, Vasylieva N, Xu J, Li P, Liu B, Zhang C, Hammock BD. 2019. Investigation of the Small Size of Nanobodies for a Sensitive Fluorescence Polarization Immunoassay for Small Molecules: 3-Phenoxybenzoic Acid, an Exposure Biomarker of Pyrethroid Insecticides as a Model. Journal of Agricultural and Food Chemistry. 10.1021/acs.jafc.9b04621.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Wang Y, Xu J, Qiu Y, Li P, Liu B, Yang L, Barnych B, Hammock BD, Zhang C. 2019. Highly Specific Monoclonal Antibody and Sensitive Quantum Dot Beads-Based Fluorescence Immunochromatographic Test Strip for Tebuconazole Assay in Agricultural Products. Journal of Agricultural and Food Chemistry 67(32):9096-9103. doi: 10.1021/acs.jafc.9b02832.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Chen H, Ding Y, Yang Q, Barnych B, Gonzalez-Sapienza G, Hammock BD, Wang M, Hua X. 2019. Fluorescent "Turn off-on" Small-Molecule-Monitoring Nanoplatform Based on Dendrimer-like Peptides as Competitors. ACS Appl mater Interfaces 11(36):33380-33389. doi: 10.1021/acsami.9b13111.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Luo L, Wei X-Q, Jia B-Z, Yang J-Y, Shen Y-D, Hammock B, Dong J-X, Wang H, Lei H-T, Xu Z-L. 2019. Modulating Linker Composition of Haptens Resulted in Improved Immunoassay for Histamine. Biomolecules 9(10):597.
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Fu H-J, Wang Y, Xiao Z-L, Wang H, Li Z-F, Shen Y-D, Lei H-T, Sun Y-M, Xu Z-L, Hammock B. 2020. A rapid and simple fluorescence enzyme-linked immunosorbent assay for tetrabromobisphenol A in soil samples based on a bifunctional fusion protein. Ecotoxicology and Environmental Safety. 188: 109904. https://doi.org/10.1016/j.ecoenv.2019.109904.
|
Progress 11/06/17 to 09/30/18
Outputs
Target Audience:We have more than a target audience, we have a user audience. The 60+ assays that we have developed are listed on our web site, and we provide reagents gratis to any non profit organization that requests them. The requests are largely California but obviously also international. Through electronic communication, publications and meetings we reach the research communities. We also provide these reagents and information to a variety of agencies including NIEHS, FDA, EPA, NIDDK, NINDS, NIOSH and others at the Federal Level and Department of Pesticide Regulation in California. Many of these assays are used for human exposure monitoring, but this year we were involved in a wildlife biology project monitoring prarrie dogs. We thought consumer groups would be interested in using the tools to check fresh market produce, but this market never evolved. Our work is largely related to food and environmental contamination and indirectly to human health. However, some of our assays are of clinical importance including the cancer markers discussed and an inflammation marker. Particularly with nanobodies we are looking into therapeutic applications. In addition to the reagents our advanced technology such reporter technologies and particularly in pioneering the development of nanobodies to small molecules are finding places in the immunodiagnostic field in general. Changes/Problems:We anticipate no changes or major problems. Like in the early days of monoclonal antibodies in the 1970s years of work by many laboratories are critical before the new technology becomes well established internationally. Already it is clear that nanobody and other recombinant antibody and phage display technologies are far more cost effective and powerful than existing technology. Our research emphasis may change somewhat as new opportunities open and problems emerge. What opportunities for training and professional development has the project provided?Training and providing professional development for undergraduate and graduate students, postdoctoral fellows and senior scientists is an on-going activity in the lab. The primary goal is the development of new immunoassays and their application to human, livestock and environmental health. Over the last period we published 12 peer reviewed papers in this area including assays for pesticides, bioterror agents, hormones, mycotoxins, cancer markers, and others. The assay reagents have been provided to laboratories around the world. A major outreach accomplishment was hosting a national meeting on environmental chemicals including immunodiagnostics with over 450 participants held in Sacramento for 4 days. We continue to give talks at national and international meetings including video lectures with an immunoassay institute being formed in China. Two laboratory scientists visited China to train scientists in immunoassay. We continue to host graduate students, postdoctoral fellows and senior scientists from around the world for 6-18 months to learn immunoassay and particularly nanobody technology. The laboratory size in this area has ranged from 10-16 during the reporting period. Of note we have obtained 5 years of interdisciplinary funding to address pesticide contamination in Northern California resulting from cannabis culture working closely with the Yurok nation. We have held and participated in multiple events with the tribe. How have the results been disseminated to communities of interest?This is in part covered above. In addition to peer review publication, training of UCD and visiting scientists and students, international lectures and classes, and hosting a large national meeting in Sacramento, we have worked closely with the Yurok nation on exposure to pesticides associated with illegal cannabis culture. What do you plan to do during the next reporting period to accomplish the goals?Continue effort to generate resources to carry out and discriminate research results related to the the above goals. Then use the funds effectively in innovation, communication and training in the field.
Impacts
What was accomplished under these goals?
The accomplishments are clear from the peer reviewed publications listed. Several accomplishments are of particular note. Pesticide contamination is of high interest to the public, but examining contaminants in the environment by broad screening methods and also looking at actual human exposure pesticides are not a problem for the general population. Similarly, when we look at the potential toxicity of the pesticides to man and the environment pesticides are of generally low risk. Perceived risk is of course not unimportant so we continue to develop and apply pesticide assays. For example, in the fear of fipronil contaminated eggs in Europe, our immunoassay was used for some of the monitoring. In the US the speed and low cost of the assay could be used to increase consumer confidence. Although fipronil is of remarkably low apparent toxicity to mammals it is an environmental problem and very similar to the highly toxic bioterror weapon TETs. We have developed the first immunoassay for TETs and it is not only field portable but far more sensitive than GLC or LC MS. We also found and synthesized a fipronil metabolite useful for human monitoring of TETs and elsewhere we report that surprisingly it can lead to Alzheimer's like lesions in human cells and mice. Although pesticides do not appear to be a major risk based on exposure levels, human monitoring or innate toxicity this is not true for all environmental and food contaminants. Human exposure to personal care products is very high. As an example, for the last 15 years we have argued that the potential risks of the additives triclosan and triclocarban exceed their benefits in most situations. Our effort have supported the dramatic decrease in the use of these materials as `value added products' without banning them since they do have a few reasonable uses. A similar impact resulted from our work on halogenated fire retardants. Increasingly we have developed assays for biomarkers of human exposure to chemicals and disease causing agents and there is the chance to use some of these reagents therapeutically in the future. As we continue developing and applying new methods, we explore improved signal transduction systems to increase speed and sensitivity of the technology. However, by far the major contribution we have made is advancing the use and technology of producing FAB and VHH fragments (nanobodies) to provide small, reproducible, efficient reagents in an unlimited supply. As in previous years our productivity of funding ratio remains infinitely large with multiple peer reviewed publications (as one indicator) and no resources. As an over view we have made further progress in using immunoassays to monitor environmental chemicals of concern to human health and agriculture and to develop and advance new analytical technologies to accomplish the objectives of this project.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2017
Citation:
Chu, S., M.R. Baker, G. Leong, R.J. Letcher, S.J. Gee, B.D. Hammock and Q. Li. 2017. Exploring Adduct Formation between Human Serum Albumin and Eleven Organophosphate Ester Flame Retardants and Plasticizers Using MALDI-TOF/TOF and LC-Q/TOF. Chemosphere. 180:169-177. PMID: 28407546.
- Type:
Journal Articles
Status:
Published
Year Published:
2017
Citation:
Vasylieva, Natalia; Barnych, Bogdan; Rand, Amelia ; Inceoglu, Bora; Gee, Shirley; Hammock, Bruce. 2017. Sensitive immunoassay for detection and quantification of the neurotoxin, tetramethylenedisulfotetramine (TETS). Anal. Chem. 89(10):5612-5619. PMID: 28398746.
- Type:
Journal Articles
Status:
Published
Year Published:
2017
Citation:
Li, D., Y. Cui, C. Morisseau, S.J. Gee, C.S. Bever, X. Liu, L. Tang, B.D. Hammock and Y. Ting. 2017. Nanobody based Immunoassay for Human Soluble Epoxide Hydrolase Detection using PolyHRP for Signal Enhancement --the Rediscovery of PolyHRP? Anal. Chem. 89(11):6248-6256. PMID: 28460522.
- Type:
Journal Articles
Status:
Published
Year Published:
2017
Citation:
Barnych B, Vasylieva N, Joseph T, Hulsizer S, Nguyen HM, Cajka T, Pessah I, Wulff H, Gee SJ, Hammock BD. Development of Tetramethylenedisulfotetramine (TETS) Hapten Library: Synthesis, Electrophysiological Studies, and Immune Response in Rabbits. Chemistry (Weinheim an der Bergstrasse, Germany). 2017;23(35):8466-72. Epub 2017/04/16. doi: 10.1002/chem.201700783. PubMed PMID: 28411375; PMCID: PMC5808876.
- Type:
Journal Articles
Status:
Published
Year Published:
2017
Citation:
Vasylieva, N., B. Barnych, D. Wan, E.A. El-Sheikh, H.M. Nguyen, H. Wulff, R. McMahen, M. Strynar, S.J. Gee and B.D. Hammock. 2017. Hydroxy-fipronil as a new urinary biomarker of exposure to fipronil. Environ Int. 103:91-98. PMID: 28343720.
- Type:
Journal Articles
Status:
Published
Year Published:
2017
Citation:
Liu X, Tang Z, Duan Z, He Z, Shu M, Wang X, Gee SJ, Hammock BD, Xu Y. Nanobody-based enzyme immunoassay for ochratoxin A in cereal with high resistance to matrix interference. Talanta. 2017;164:154-8. Epub 2017/01/22. doi: 10.1016/j.talanta.2016.11.039. PubMed PMID: 28107910.�
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Jeon J, Uthaman S, Lee J, Hwang H, Kim G, Yoo PJ, Hammock BD, Kim CS, Park Y-S, Park I-K. In-direct localized surface plasmon resonance (LSPR)-based nanosensors for highly sensitive and rapid detection of cortisol. Sensors and Actuators B: Chemical. 2018;266:710-6. doi: https://doi.org/10.1016/j.snb.2018.03.167.�
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Huo J, Li Z, Wan D, Li D, Qi M, Barnych B, Vasylieva N, Zhang J, Hammock BD. Development of a Highly Sensitive Direct Competitive Fluorescence Enzyme Immunoassay Based on a Nanobody-Alkaline Phosphatase Fusion Protein for Detection of 3-Phenoxybenzoic Acid in Urine. J Agric Food Chem. 2018. Epub 2018/10/09. doi: 10.1021/acs.jafc.8b04521. PubMed PMID: 30293433.�
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Chen H, Yang Q, Ding Y, Vasylieva N, Bever CS, Hua X, Wang M, Hammock BD. Competitive and noncompetitive immunoassays for the detection of benzothiostrobin using magnetic nanoparticles and fluorescein isothiocyanate-labeled peptides. Anal Bioanal Chem. 2018. Epub 2018/11/28. doi: 10.1007/s00216-018-1478-8. PubMed PMID: 30478514.
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Lassabe G, Kramer K, Hammock BD, Gonzalez-Sapienza G, Gonzalez-Techera A. Noncompetitive Homogeneous Detection of Small Molecules Using Synthetic Nanopeptamer-Based Luminescent Oxygen Channeling. Anal Chem. 2018;90(10):6187-92. Epub 2018/04/26. doi: 10.1021/acs.analchem.8b00657. PubMed PMID: 29694028; PMCID: PMC5963685.�
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Bever CS, Rand AA, Nording M, Taft D, Kalanetra KM, Mills DA, Breck MA, Smilowitz JT, German JB, Hammock BD. Effects of triclosan in breast milk on the infant fecal microbiome. Chemosphere. 2018;203:467-73. doi: https://doi.org/10.1016/j.chemosphere.2018.03.186.�
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Cui X, Vasylieva N, Shen D, Barnych B, Yang J, He Q, Jiang Z, Zhao S, Hammock BD. Biotinylated single-chain variable fragment-based enzyme-linked immunosorbent assay for glycocholic acid. Analyst. 2018;143(9):2057-65. doi: 10.1039/C7AN02024D.�
- Type:
Journal Articles
Status:
Published
Year Published:
2017
Citation:
Cui X, Vasylieva N, Wu P, Barnych B, Yang J, Shen D, He Q, Gee SJ, Zhao S, Hammock BD. Development of an Indirect Competitive Enzyme-Linked Immunosorbent Assay for Glycocholic Acid Based on Chicken Single-Chain Variable Fragment Antibodies. Analytical Chemistry. 2017;89(20):11091-7. doi: 10.1021/acs.analchem.7b03190.�
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Pali M, Bever CRS, Vasylieva N, Hammock BD, Suni II. Impedance Detection of 3-Phenoxybenzoic Acid with a Noncompetitive Two-site Phage Anti-immunocomplex Assay. Electroanalysis.0(0). doi: doi:10.1002/elan.201800457.��
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