Protecting Human Health


Nanotechnology-Enabled Sensors: 

A sensor is a device that responds to a physical, chemical, or biological parameter and converts that response into a signal or output. Applications of sensors include national security, medicine and health, environmental monitoring, and food safety. Nanotechnology plays a significant role in several aspects of sensor development.

Seamlessly Integrating Biological Molecules with Nanoparticles

Researchers at the Naval Research Laboratory (NRL) are developing nanotechnology-enabled constructs (or nanoconstructs) that seamlessly integrate biological molecules, such as proteins and DNA, with nanoparticles. These hybrid nanomaterials will lead to breakthrough energy harvesting and lightweight systems, as well as technologies to protect soldiers in the future, including biosensors, counteractive materials, and medicines. Realizing that the development of nanoconstructs would require a multidisciplinary approach drawing from biology, materials science, physics, and chemistry, scientists from the Center for Biomolecular Science and Engineering and the Optical Sciences Division teamed together under the auspices of NRL’s Institute for Nanoscience. Their “toolbox” for nanoconstructs has already been used in diverse applications such as single-cell pH nanotechnology-enabled sensors (nanosensors), enzymatic nanosensors, cellular labels, light harvesting nanoarrays, photonic wires and switches, rulers for nanoscale measurements, and for decorating targeted proteins inside

 NRL has fabricated nanoplasmonic arrays to  image cells protein secretions onto standard  glass coverslips, reinforced with a silicon  backing ring. Photo courtesy of U.S. Naval  Research Laboratory/Jamie Hartman

a living cell with quantum dots for intracellular protein dynamic analyses. The U.S. Food and Drug Administration, the Army Medical Research Institute of Infectious Diseases, and the U.S. Army Engineer Research and Development Center have all adopted NRL nanoconstruct designs to detect foodborne, aerosolized, and infectious biothreat pathogens, respectively. NRL-enabled development of nanoscale probes and cellular delivery vehicles provides scientists with a new generation of tools for early investigation and treatment of disease at the molecular level.

Low-Power, Lightweight, and Tunable Carbon Nanotube-Based Sensors

For more than a decade, scientists and engineers at the NASA Ames Research Center have been developing nanosensors, with particular emphasis on those derived from carbon nanotubes (CNTs). These sensors are compact, can operate at low power levels, and can be tuned to detect specific chemical and biological substances. They also can be readily integrated into portable electronics such as smart phones to create a lightweight sensor platform with GPS-enabled location information and, through Wi-Fi or cellphone communication networks, a system of distributed sensors. CNT-based sensors have broad applications ranging from detecting chemical and biological indicators for life on other planets, to providing early warning of the release of toxic chemicals due to an accident or terrorist attack. They can also be used in the screening of chemicals and biomarkers for the early detection of disease. A CNT sensor developed by the NASA Ames Research Center was incorporated into a compact electronic nose and successfully flight tested on the International Space Station in 2009. This sensor technology was  A chemical-sensing prototype plugged  into an iTouch 30-pin dock connector with  the display-side up. Photo courtesy of  NASA

the recipient of a Nano-50 Innovator Award in 2008 and NASA’s H. Julian Allen Award in 2012. In late 2011, NASA Ames worked with the Los Angeles Fire Department to demonstrate a CNT-based sensor as part of a handheld detector. The firefighters used the detector for identifying toxic materials released during a fire and to create a sensor network for establishing a safe perimeter around fires.

Monitoring Crop Infection on Site

About $9 billion worth of crops are lost to disease each year in the United States, largely due to the inability to accurately monitor crop infection on site in a timely manner. A point-of-use detection technology that enables quicker and simpler diagnoses will ensure a faster response and a reduction in crop loss. A research team at Cornell University, funded through the USDA National Institute of Food and Agriculture, has developed a DNA nanobarcode technology for detecting crop pathogens. Like supermarket barcodes, the DNA nanobarcodes can be easily scanned and decoded to identify pathogen types. The goal of this research is to develop a portable device that rapidly detects disease without sophisticated equipment or training. The group developed the breakthrough technology by engineering DNA into X- and Y-shaped structures. They used these structures to construct DNA nanobarcodes: nanometer-sized branched DNA trees that carry a unique fluorescence color ratio. For example, 1 green dye and 2 red dyes or 4 green dyes and 1 red dye are fluorescent codes associated with specific pathogens. With further development, farmers may be able to monitor and diagnose their crops, saving time and money, and allowing for a more rapid response to control infection. Importantly, this DNA nanobarcode assay is inexpensive; each assay can rapidly detect multiple pathogens simultaneously and costs less than $2.

Transporting Proteins on a Lab-on-a-Chip

Nanostructured catalytic systems, or artificial motors, may one day be used in everything from cancer diagnosis to neutralizing chemical weapons. Professor Joseph Wang and co-workers at the University of California at San Diego, funded through the Defense Threat Reduction Agency, have shown that functionalized nanostructured catalytic systems can capture and transport target proteins between different reservoirs of a lab-on-a-chip device. These systems also change speed as a function of the concentration of toxin present in solution, similar to the way fish change their behavior during water toxicity testing. Potentially, this research can lead to a new strategy for simple and cost-effective water quality testing. It may also be used in the sensing and remediation of chemical or biological threats within a variety of environmental and biological matrices.

 

Nanotechnology-Enabled Diagnostics and Therapeutics: 

The medical applications of nanotechnology offer the unique opportunity to detect functional changes at the molecular or cellular levels, thus enabling the possibility for early diagnosis and improved prognosis.

Accurate and Efficient DNA Sequencing

Achieving low-cost and rapid DNA sequencing is necessary to reach the full potential of genomics for improving human health. The National Institutes of Health National Human Genome Research Institute (NHGRI) 2013 Advanced DNA Sequencing Technology program focused on the use of nanopore technology in developing more accurate and efficient DNA sequencing. The advantages of nanopore-based techniques include real-time sequencing of single DNA molecules at low cost and the ability for the same molecule to be reassessed and verified. Additionally, very long segments (10s of kilobases) can be sequenced. Previous systems involve isolating DNA, chemically labeling it, and copying it. In this process, DNA has to be broken up into smaller segments (about 800 base pairs). Nanopore sequencing simplifies the process since it only requires isolation of the DNA in preparing it for sequencing. Dr. Jens Gundlach of the University of Washington is continuing to develop the use of nanopore DNA sequencing technology using a type of protein nanopore. Part of his group’s research focuses on improving the control of movement of DNA through the nanopore and on developing algorithms to identify DNA bases. Professor Mark Akeson at the University of California at Santa Cruz is using a natural DNA-copying enzyme to ratchet a DNA strand back and forth through an engineered biological nanopore. This method is designed to address the technical challenges

 

Nanopore-based DNA sequencing concepts generally entail one of the DNA strands passing through the nanopore sensor, where the individual nucleotides (DNA building blocks) are distinguished from each other. Photo courtesy of Jonathan Bailey, NHGRI

for many groups working on nanopore sequencing in both the academic and commercial worlds of slowing down the rate at which DNA travels through a nanopore and reading DNA strands multiple times. A number of small companies, such as Genia (purchased by Roche in 2014) and Nabsys, have also benefited from NHGRI funding to help commercialize nanopore DNA sequencing systems. Commercialization of these technologies holds the promise of solving the long-standing problems of obtaining accurate sequence reads of 10,000 to 100,000 bases or more. Over the past year (since spring 2014) one company that has licensed intellectual property generated through several NHGRI-funded grants on nanopore sequencing has engaged dozens of investigators worldwide in an early access program for a commercial nanopore sequencer, resulting in nearly two dozen publications. Private sector investment in several companies in this space has increased. The method clearly works and it now remains to be seen how it will fare in the commercial and scientific landscape.

A Promising Vehicle for Treating Skin Diseases

The first step in gene therapy involves delivering nucleic acids (DNA or RNA) into cells. Traditional methods of delivery, which work well in cell cultures, are not very effective in delivering nucleic acids through human skin. This is because our skin is designed to be a barrier against the entry of bad agents, such as pathogens and toxins, and the exit of water from the body. A multidisciplinary research team at Northwestern University, funded in part by the National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and led by Drs. Amy S. Paller and Chad Mirkin, invented a way to overcome this obstacle. They are using a new delivery system of spherical nucleic acid nanoparticle complexes (SNA-NCs) in which RNA molecules are attached to gold nanoparticles. When tested on cultured keratinocytes, the cells that form the skin barrier, virtually all of the SNA-NCs were ingested. The researchers recently showed that it actually worked for human skin in vivo and have discovered that the complexes have many desirable properties such as low toxicity, long-lasting action, and hypoallergenicity. As a result, SNA-NCs are very promising vehicles for skin gene therapy, the treatment of many rare hereditary skin diseases such as pachyonychia congenita, and for helping painful diabetes-related ulcers heal.

 

 

Studying the Effects of Nanotechnology-Enabled Materials on Human Health: 

As researchers work to improve our lives through nanotechnology, efforts are also underway to understand the potential impacts of nanomaterials on our health. Ensuring that people safely benefit from nanotechnology is one of the four goals of the National Nanotechnology Initiative.

Developing Guidelines for Safe Development and Use of Nanotechnology

Recognizing that engineered nanomaterials are becoming more common in products of daily life, such as drugs, cosmetics, electronics, toys, and laundry machines, the National Institutes of Health National Institute of Environmental Health Sciences (NIEHS) has an active research program on nanotechnology environmental health and safety (nanoEHS) research. This includes efforts through extramural research funding, the National Toxicology Program (NTP), and modest intramural research. The recently concluded research program, NIEHS Centers for Nanotechnology Health Implications Research (NCNHIR), included investigators across the United States that studied the interactions of about 30 engineered nanomaterials (ENMs) with biological systems and utilized that knowledge to develop predictive models for hazard ranking and health effects assessment. The ENMs investigated included metals, metal oxides, quantum dots, fullerenes, and single/multiwall carbon nanotubes. These efforts led to about 200 peer-reviewed publications and an online tool, In vitro Sedimentation, Dissolution and Dosimetry (ISDD model) for calculating dosimetry for metal ENMs in vitro studies. The program is developing plans to continue funding through new consortium approaches to address key scientific gaps and research needs of NNI regulatory agencies. NTP carried out short- and long-term good laboratory practice studies on C60 fullerenes, silver, and multi-walled carbon nanotubes. The results of these studies are being analyzed. The NIEHS nanoEHS program hopes to provide the scientific underpinnings needed to develop guidelines for the safe development and use of nanotechnology by focusing on the most commonly produced and used ENMs.

Working towards the Safe Use of Nanotechnology in the Environment

Researchers also are looking at the potential impacts of nanotechnology-enabled products on the environment once they enter the waste stream. The mission of the NSF- and EPA-funded University of California Center for Environmental Implications of Nanotechnology (UC CEIN) is to use a multidisciplinary approach to conduct research, knowledge acquisition, education, and outreach to ensure the responsible use and safe implementation of nanotechnology in the environment. The Center’s streamlined approach combines predictive hazard and exposure assessment methods, high-throughput discovery platforms, and environmental decision-making tools. By examining a wide range of interactions between nanoparticles and organisms in both terrestrial and aquatic ecosystems, the Center is effectively implementing a 21st-century paradigm for the safe use of nanotechnology in the environment.