Duration: 10/01/2021 to 09/30/2026

Administrative Advisor(s):

NIFA Reps:

Non-Technical Summary

Statement of Issues and Justification

The mission of the USDA is to “provide leadership on agriculture, food, natural resources, rural infrastructure, nutrition, and related issues through fact-based, data-driven, and customer-focused decisions.” This implies a commitment to sustain vibrant rural economies, healthy ecosystems, and a safe and secure food supply. The COVID-19 pandemic has underscored that this mission also intersects public health and worker safety, as essential workers in the agriculture and food industries are vulnerable to emerging infectious diseases. Addressing these challenges in the 21^st Century requires a suite of distributed technologies to monitor the natural world in real-time, analyze aggregated data in the context of the high biological and climatological complexity, and adaptively address threats and opportunities for improving desired outcomes. As cellular and molecular processes are foundational to all of these outcomes, realizing this potential will require new biosensor technologies, systematic study of nano scale processes and materials, remote networking, and artificial intelligence to provide decision support from complex aggregated data.

Nanotechnology and Biosensors address the mission of USDA in numerous intersecting ways. For example, simple, rapid, and affordable biosensor technologies are critical for rapidly identifying and responding to pathogen and pest outbreaks affecting people, plants, and animals, including the novel coronavirus SARS-CoV-2. Biosensors are also critical for quality control in bioprocessing, identification of environmental contaminants, and evaluating food safety and quality. Advances in biosensor performance are often predicated on novel nano materials, or exploitation of nanoscale phenomena. Advances in nanotechnology may also underlie effective technologies for delivery of therapeutic compounds and vaccines to safeguard the health of humans, plants, and animals. To this end we propose to renew a research project with the broad topic of Biosensors and Nanotechnology, with specific research effort addressing the following:

• Characterization of nanomaterials, including morphology, toxicity and its underlying mechanisms, stability, cellular uptake and transport, environmental fate and transformation, and interaction with biological organisms, materials, and other substances;
• Synthesis of one- and two-dimensional nanomaterials (e.g., graphene, phosphorene) via bottom-up or top-down approaches, with novel properties for applications such as improved biosensor performance, enhanced nutritional value, inhibition of bacterial growth or adhesion, or remediation of environmental contaminants; 
• Antimicrobial resistance, including sensors for detection and mitigation of multi-drug resistant pathogens, and investigation of novel antimicrobial nanomaterials and processes.
• Synthetic biology and engineered organisms, viruses, and nanoparticles for sensing applications, delivery of genes and therapeutic compounds, or vaccine development;
• Implementation of smart agriculture through remote sensor networks and “big data” approaches to systematically extract and analyze data generated from nanotechnology and nanomaterial-related research that are difficult to analyze using traditional data processing methods;
• Novel approaches for sensing and diagnosing emerging infectious diseases in plants, animals, humans, and in the environment.

Related, Current and Previous Work

Nanotechnology and biosensors may present a double-edged sword to food and agricultural systems. They hold great promise to improve life quality (e.g. Cao et al., 2005; Cui et al., 2001; Diallo et al., 1999; Elliott and Zhang, 2001; Kong et al., 2000; Nicewarner-Peña et al., 2001; Waychunas et al., 2005; Wu et al., 2005; Yue and Economy, 2005). The performance of biosensors is known to be enhanced when nanomaterials are incorporated in at least one active component (e.g., electroactive materials, photocatalysts, superparamagnetic materials). However, some materials may have inherent risk of negative environmental and/or human health impacts upon release to water, air, soil or food systems (Dreher, 2004; Halford, 2004; Renwick et al., 2004; Soleymani and Li, 2017). Despite the rapid development of these technologies recently, there are still fundamental and applied knowledge gaps that limit the practical and commercial application of nanotechnology and biosensors to agricultural systems.

During the current 5-year period of NC-1194 project numerous contributions have been made towards achieving the previously identified milestones.

1. Notable advances were made in validation of the biosensors and other devices in real matrices.
   • Innovative nanoparticle morphologies were developed for enhanced Surface Enhanced Raman Scattering (SERS) for pesticide analysis (MO), investigating metabolite distributions in plant and animal cells (IA, UT), and to enhance performance of a variety of other biosensing modalities including for microbial and chemical contaminants in food and water (AR, AZ, FL, HI, IA, MI, WI).
   • Multidisciplinary collaborations have been established to address topics of antimicrobial resistance, advancing affordable technologies for rapid clinical identification of antimicrobial resistance in pathogenic bacteria (MI), and novel approaches to preventing and treating infections with pathogenic organisms demonstrated successfully in animal models (SC).
   • To support commercialization of new technologies participants contributed to the development of open source smart-phone based approaches for portable analysis (AR, AZ, HI), scalable disposable sensors including using paper microfluidics (AZ), scalable manufactured graphene (FL, IA), as well as stabilization of immobilized biomaterials (GA).
   • Significant progress was made in characterizing and understanding mechanisms of toxicity of a wide array of commonly used nanomaterials (KY, WI).
   • New nanomaterials have been developed for targeted drug delivery (AR, IA) or vaccines against animal viruses (VA), to prepare edible films with novel antimicrobial and nutritional properties (NJ), to improve efficiency / rates for value-added bioprocessing (AR, WI), and enhance speed and sensitivity for recovery and detection of pathogenic bacteria (AR, MI, NY).
   • Participants have been working on modeling of networking approaches and artificial intelligence to aggregate data and provide meaningful decision support to improve food quality, safety, and the cost-effectiveness of agriculture and bioprocessing (AR, AZ, FL, MI, NJ).
2. Potential industry partners were identified to assess market-readiness of the developed technologies.

The partnerships were formed with the Global Alliance for Rapid Diagnostics (GARD) to establish centers of excellence (COEs) around the world, and agreements with food companies to validate and license technologies for rapid pathogen extraction / detection (MI). Walmart foundation awarded $3.5 M to a group lead by a project member from Arkansas for research on biosensors for food safety. A consortium of University groups including participants in this project (FL, IA) are actively involved in a funded planning grant under NSF-IUCRC (Industry-University Cooperative Research Center) to use nano-enabled sensory tools for soil dynamics research. Members of NC 1194 are active leaders in the new NSF-ERC IoT4Ag, focused on wireless sensing networks for agriculture. Technologies, developed by members of our group, have successfully been used by government and industry (e.g., handheld biosensors for bacteria in drinking water are used by Tucson Water (AZ)). Participants at Clemson are working with SBIR funding to develop new mobile device APIs to facilitate risk analysis in water quality.

3. Teaching and training materials related to nanotechnology and biosensors were developed and disseminated through publications, conferences and workshops.

Outputs  over 5 years include over 200 peer-reviewed publications in high impact journals.  The research has been regularly highlighted as the feature articles in their respective issues, and / or covered in the scientific press (e.g., NSF Research News and CEP Magazine) (AZ). Participants have notably made publicly available several research tools to help identify relevant research in biosensors, for example the open source sensor search engine (SENSEE) tool developed by NC1194 members in FL, SC and IA. In addition, members have shared protocols for research related to biosensors and antimicrobial resistance (IA, MI).

Numerous training materials have been developed by members in FL, SC and IA, including protocols for biosensor development and testing and manuals for educational camps targeting pre-collegiate youth (in collaboration with 4H).

Impacts

Over 5 years this project supported training of new scientists researching innovative nanomaterials and biosensors (PhD students, undergraduate students and high school students) and enhanced global networking of researchers with work related to nanotechnology and biosensors. Walmart foundation awarded $3.5 M to a group led by a project member from Arkansas (Yanbin Li) for research on biosensors for food safety. A project member (Eric McLamore) was awarded a NIFA Center of Excellence for development of smart sensor technologies in agriculture ($5 M by Water for Food Program). Numerous technologies have been developed in these efforts and other projects led by NC1194 members that advance the key needs to enable broad distribution of biosensors in a wide variety of applications, including speed to detection, ease of use / portability, scalability / manufacturability, sensitivity / selectivity, and data management / analysis. In addition, research has resulted in a variety of innovative use of biological and nanoscale materials for vaccine development, drug delivery and therapies against pathogenic organisms by NC1194 members. This leadership is anticipated to be especially important in a post-pandemic supply chain where the connection between food-energy-water-sanitation-health is more apparent than ever. In addition, members are leaders in the area of toxicological research, where data on widely used nanomaterials can inform policy decisions related to manufacturing and exposure to these materials to safeguard public and environmental health. Our team recently submitted an invited review connecting these metadomains and calling for continued convergence to advance the field of agriculture.

Objectives

1. Develop new technologies for characterizing fundamental nanoscale processes and fabricate self-assembled nanostructures
   
2. Develop devices and systems incorporating nanotechnology and data-driven analytics for detection of biological/chemical targets, with an emphasis on detection of infectious diseases in plants, animals, humans, and the environment
   
3. Advance the integration of novel sensor networks, information systems, and artificial intelligence for effective risk assessment and decision support for food security and safety
   
4. Develop and update education and outreach materials on nanofabrication, sensing, systems integration and application risk assessment.
   
5. Increase the number academic-industry partnerships to help move the developed technologies to commercialization phase.
   

Methods

Multidisciplinary experimentation and modeling methods at different scales will be used to fulfill the objectives. We will use bench-scale and field-scale experimentation and modeling methods to investigate the application and implication of nanotechnology in agricultural and biological systems. These methods can be summarized as: 1. Bench-scale Investigation: Laboratory experiments will be conducted to synthesize, and characterize the physical-chemical properties, potential toxicity and mechanisms of formation various types of nano-based materials, as well as their applications. For example, to investigate toxicity of as-synthesized and transformed nanomaterials, model animal and plant organisms (e.g., nematode, legume, mice) with well-known genetics and a plethora of available genomic tools will be used. Similarly, potential antimicrobial therapies against multidrug-resistant pathogens will be tested in vivo in animal models.  In silico simulations will be developed for common types of electrodes (e.g., impedance biosensors, surface plasmon resonance biosensors) and coupled with emerging sensor databases to drive new research directions in the area of data-driven decision support. Thus, bench scale investigations will also include development of cyber-physical biosensor systems using a common smartphone as the enabling platform (including cyber security, data acquisition, data analysis, and decision support) 2. Field-scale Investigation: Field-scale experiments will be used to evaluate the application of portable and installed sensors, including the impact of: i) data derived from biosensors, and ii) the affect(s) of nanotechnology on agricultural and environmental systems under realistic exposure scenarios. Complexity and uncertainty analysis will be used to model the behavior of materials in field-scale investigations based on established models. Mathematical models will be used to bridge bench scale and field scale investigations, inform the analysis across multiple scales and serving as a bridge across these two important pillars of NC-1194 research. Newly developed educational materials will emphasize an active learning approach, and learning outcomes from educational modules will be evaluated using direct formative methods. Aggressive outreach to industry will be done through direct communication to potential partners, as well as broad stakeholder invitation to research symposia and workshops let by members of this group at professional meetings and through professional societies such as ASABE, SBE, and IFT.

Measurement of Progress and Results

Outputs

• Research articles in peer reviewed journals and publications, presentations at national and international meetings, and workshops and patents
• Course modules on different aspects of nanotechnology and biosensors, which are accessible to the educational community and public
• Workshops and seminars on nanotechnology and biosensors with proceedings of the workshops made available to the public
• Web-based resource clearing house for educational communities and the public
• Prototype nano-biosensors incorporating nanoparticles, nanowires, nanofibers, nanobars, nano-pillars, and nanopores
• Field-deployable prototype devices tested with bacteria, viruses, and toxins, chemicals, and other contaminants that are ready for potential commercialization
• Development of prototype nano-biosensors including specifications for the design and synthesis of corresponding nanomaterials
• Development of biosensor systems for single-cell and single virus analysis
• Development of wireless systems for improving data-driven decision support in agriculture
• A data repository (Zenodo) for sensors, sensor data, and protocols related to agricultural and environmental biosensing and nanotechnology

Outcomes or Projected Impacts

• Greater understanding of nanotechnology by the public
• Increased awareness and numbers of applications of nanotechnology in agricultural and biological systems
• Increased numbers of students from land grant universities skilled in the scientific methods and applications of nanotechnology
• Development of tools and products which exploit the novel properties of nanomaterials and nanoscale devices and benefit different aspects of agriculture and biological engineering research
• Increased understanding of the fundamental nanoscale phenomena and processes in food and agricultural products as well as the processes and analytical devices that apply to these products
• Tools for the performance assessment new techniques and devices, and guiding engineering improvements within a theoretical context
• Development of nanoscale devices and systems that will advance the capabilities of currently designed devices for higher performance (sensitivity, speed of detection, and applications for example)
• Increased accessibility to data and analyzed information through networked sensors and artificial intelligence-based platforms

Milestones

(2021):1. Initiate experiments to challenge self-assembled nanoparticles in complex matrices. 2. Develop a framework for economic, environmental and health risk assessment for nanotechnologies applied to food, agriculture and biological systems. 3. Optimize the performance parameters of new nanomaterials, biosensors and other devices in wireless format based on IoT metaphor. 4. Develop/improve education and outreach materials on nanofabrication, sensing, systems integration and application risk assessment. 5. Conduct annual meeting to report progress of research activities.

(2022):1. Initiate experiments to characterize new devices and systems incorporating nanotechnology and data-driven analytics for detection of biological/chemical targets. 2. Optimize the performance parameters of new nanomaterials, biosensors and other devices. 3. Proof of principle integration of novel sensor networks, information systems, and artificial intelligence for effective risk assessment and decision support using IoT metaphor. 4. Develop a joint active learning pedagogy and education strategy for the delivery of new and improved education materials. 5. Conduct annual meeting to report progress of research activities.

(2023):1. Validate methods for characterizing nanoscale processes. 2. Expand cyber-physical systems to emphasize on detection of infectious diseases in plants, animals, humans, and the environment. 3. Populate repository of educational materials on nanotechnology and biosensors and select modules to apply at multiple institutions. 4. Submit technology inventions and patent applications of developed technologies. 5. Conduct annual meeting to report progress of research activities.

(2024):1. Optimize the performance parameters of the biosensors and other devices in food, agriculture, and environmental matrices. 2. Validate use of IoT sensor networks for food security and safety in field trials and complex matrices (food, environmental samples). 3. Assess learning outcomes of educational modules applied at several institutions. 4. Improve academic-industry partnership to help move the developed technologies to commercialization phase. 6. Conduct annual meeting to report progress of research activities.

(2025):1. Continue to validate the biosensors and other devices in real matrices. 2. Identify potential industry partners and initiate meetings with these partners. 3. Assess market-readiness of the technologies. 4. Assess learning outcomes of educational modules applied at several institutions using feedback from 2024. 5. Conduct annual meeting to report progress of research activities. 6. Assess the accomplishments of NC-1194 and prepare for renewal.

Projected Participation

View Appendix E: Participation

Outreach Plan

The general educational goal of the NC-1194 committee is to provide a framework for biosensor and bio-nanotechnology education to a broad audience of agriculture and food science students outside the traditional research community (physical science/engineering graduate students). We firmly believe that undergraduates will benefit from such an education, even those who will not pursue a scientific career. These students will be the backbone of our future workforce who may be responsible for handling agricultural products and/or food safety issues, and developing science-based policies for safe use of technology to support food security and public health. 

Nanotechnology has a profound impact on society, facilitating new technical breakthroughs that in turn create new environmental and ethical challenges. To manage these complex issues, we will need future generations to understand the technology in order to make educated decisions concerning its use. Courses on modern biosensors and nanotechnology are not widely available for agricultural and food sciences students in today's college curriculum, the NC-1194 committee on nanotechnology and biosensors is uniquely positioned to address these educational needs and serve our students' best interests. 

To achieve these goals, the committee will expand on previous accomplishments to 1. Implement a course-material sharing mechanism. McLamore from Clemson University (formerly FL) has established an open source protocol for hosting content on Zenodo that will be expanded for this purpose. Available materials to be shared include course materials developed at MSU, Univ. of Arizona, Clemson, ISU, Purdue and Univ. Hawaii. By generating this hub for teaching materials, our students will be greatly benefited as they can gain access to a much broader range of learning materials beyond their own institution. 2. Continue to utilize the open-bioinstrumentation potentiostat developed by Jenkins from Univ. of Hawaii for field analysis. Members have published at least 10 manuscripts using this instrument developed as part of our previous 5-year milestones.

Institutions using learning modules will require that students prepare brief videos on their work that will be selected and distributed to high schools for increased outreach and dissemination of STEM disciplines through nanotechnology and biosensors.

One aspect of nanotechnology that is of particular interests to the general public is the potential impact of nanomaterials to human, animal and environmental health and development of environmentally safe technologies.  We have recruited participants with expertise in environmental and health nanotoxicity (KY and SC).

Organization/Governance

NC-1194 is organized according to the guidelines in the USDA Multistate Research Handbook, as found at https://www.ncra-saes.org/multistate-handbook. Membership includes an administrative advisor (Dr. Steven Lommel from NC State University), a CSREES representative (Dr. Hongda Chen) and project leaders from cooperating stations. Meetings are held annually. The secretary for the coming year is elected at the end of each meeting. The previous secretary advances to vice-chair and the vice-chair to chair. These three officers, the past chair, and the administrative advisor constitute the executive committee. The dates of the annual meeting (typically two or three days) are determined by the host and the chair after consulting the Committee at the preceding meeting and throughout the project year. The chair develops an agenda for the upcoming meeting in consultation with the executive committee and feedback from the membership. The annual meeting includes technical reports from each represented station, discussion of results and future areas of collaboration, and meetings among smaller ad hoc committees. The location of the meeting for the coming year is determined by vote at the end of each meeting, though it may potentially be changed as new opportunities or challenges arise. Where possible meetings are held in conjunction with a conference of a related professional organization. Minutes are prepared by the secretary and sent to members. An annual report is prepared by the chair, submitted to the administrative advisor, and posted at the NC-1194 web site.

Literature Cited

Cao, J., Elliott, D., Zhang, W., 2005. Perchlorate Reduction by Nanoscale Iron Particles. J. Nanoparticle Res. 7, 499–506. https://doi.org/10.1007/s11051-005-4412-x

Cui, Y., Wei, Q., Park, H., Lieber, C.M., 2001. Nanowire Nanosensors for Highly Sensitive and Selective Detection of Biological and Chemical Species. Science 293, 1289–1292. https://doi.org/10.1126/science.1062711

Diallo, M.S., Balogh, L., Shafagati, A., Johnson, James H., Goddard, W.A., Tomalia, D.A., 1999. Poly(amidoamine) Dendrimers:  A New Class of High Capacity Chelating Agents for Cu(II) Ions. Environ. Sci. Technol. 33, 820–824. https://doi.org/10.1021/es980521a

Dreher, K.L., 2004. Health and Environmental Impact of Nanotechnology: Toxicological Assessment of Manufactured Nanoparticles. Toxicol. Sci. 77, 3–5. https://doi.org/10.1093/toxsci/kfh041

Elliott, D.W., Zhang, W., 2001. Field Assessment of Nanoscale Bimetallic Particles for Groundwater Treatment. Environ. Sci. Technol. 35, 4922–4926. https://doi.org/10.1021/es0108584

Halford, B., 2004. Buckyballs Damage Bass Brains. Chem. Eng. News Arch. 82, 14. https://doi.org/10.1021/cen-v082n014.p014a

Kong,  null, Franklin,  null, Zhou,  null, Chapline,  null, Peng,  null, Cho,  null, Dai,  null, 2000. Nanotube molecular wires as chemical sensors. Science 287, 622–625. https://doi.org/10.1126/science.287.5453.622

Nicewarner-Peña, S.R., Freeman, R.G., Reiss, B.D., He, L., Peña, D.J., Walton, I.D., Cromer, R., Keating, C.D., Natan, M.J., 2001. Submicrometer Metallic Barcodes. Science 294, 137–141. https://doi.org/10.1126/science.294.5540.137

Renwick, L., Brown, D., Clouter, A., Donaldson, K., 2004. Increased inflammation and altered macrophage chemotactic responses caused by two ultrafine particle types. Occup. Environ. Med. 61, 442–447. https://doi.org/10.1136/oem.2003.008227

Soleymani, L., Li, F., 2017. Mechanistic Challenges and Advantages of Biosensor Miniaturization into the Nanoscale. ACS Sens. 2, 458–467. https://doi.org/10.1021/acssensors.7b00069

Waychunas, G.A., Kim, C.S., Banfield, J.F., 2005. Nanoparticulate Iron Oxide Minerals in Soils and Sediments: Unique Properties and Contaminant Scavenging Mechanisms. J. Nanoparticle Res. 7, 409–433. https://doi.org/10.1007/s11051-005-6931-x

Wu, L., Shamsuzzoha, M., Ritchie, S.M.C., 2005. Preparation of Cellulose Acetate Supported Zero-Valent Iron Nanoparticles for the Dechlorination of Trichloroethylene in Water. J. Nanoparticle Res. 7, 469–476. https://doi.org/10.1007/s11051-005-4271-5

Yue, Z., Economy, J., 2005. Nanoparticle and Nanoporous Carbon Adsorbents for Removal of Trace Organic Contaminants from Water. J. Nanoparticle Res. 7, 477–487. https://doi.org/10.1007/s11051-005-4719-7

Attachments

Land Grant Participating States/Institutions

AR, AZ, CT, FL, HI, IA, IL, IN, KS, KY, LA, MD, MI, MN, MO, MS, NY, SC, SD, UT, VA, WI

Non Land Grant Participating States/Institutions

Iowa State University, Johns Hopkins University, University of Arkansas Pine-Bluff