SBIR-STTR Award

A general method of developing catalytic DNA biosensors for on-site, real-time, and cost-effective detection and quantification of multiple heavy metal ions, such as mercury, cadmium and lead, simultaneously will be explored. Exposure to these metal ions can bring severe health effects to human beings, such as damages to brain and kidneys, and cancers. They can also cause adverse effects on neural and brain development in children and the effects in children are often irreversible. Therefore there is an urgent need of portable sensors for these metal ions for household uses, for clinical applications in rural or remote areas, and for first-responders in the war against terrorism, where on-site, real-time, and cost-effective detection and quantification are critical. This Phase I application addresses critical issues of how to apply a successful method in designing sensors for one metal ion to those of other metal ions, and how to enhance selectivity of those sensors. It is built upon a recent success in the PI's lab where highly sensitive and selective fluorescent and colorimetric sensors for lead have been demonstrated based on catalytic DMA. In phase I, the feasibility of applying this method as the general protocol to the two other heavy metals, namely mercury and cadmium, will be investigated. Specifically, a combinatorial biology technique called in vitro selection will be carried out to select Hg(ll)- and Cd(ll)-specific catalytic DMA. After negative selection strategies are used to improve the selectivity of the selected DNA molecules, fluorescent and colorimetric sensors for mercury and cadmium will be constructed and tested by attaching fluorophore/quencher and gold nanoparticles, respectively, to the catalytic DNA molecules. After achieving these goals in Phase I, catalytic DNA specific for arsenic and chromium will be selected in Phase II and the prototype sensor kits for these heavy metal ions will be developed for testing and marketing the sensors in environmental monitoring and medical diagnostic applications.

Thesaurus Terms:
DNA, air sampling /monitoring, biohazard detection, biomedical equipment development, biosensor, catalyst, clinical biomedical equipment, heavy metal, portable biomedical equipment cadmium, lead, mercury bioengineering /biomedical engineering, colorimetry, fluorescence

Cost-effective catalytic DNA biosensors for heavy metal ions such as lead(II), uranium(VI), mercury(II), and cadmium(II) will be developed. They will be tested for on-site, real-time detection and quantification with minimal rates of false positive or false negative results. Exposure to these metal ions can cause severe adverse health effects, such as damages to brain, kidneys, and cancers, to human beings, especially children. Current technologies for metal detection employ either expensive or sophisticated instruments or simple sensors, many of which have high rates of false positive or false negative results. Therefore there is an urgent need of reliable portable heavy metal sensors for government inspectors, environmental monitors, household users, clinicians in rural or remote areas, and first-responders in the war against terrorism, where on-site, real-time, and cost-effective detection and quantification are critical and the market for heavy metal detection is estimated to be >$650 million. The project is based on several innovations in the PI's group at the University of Illinois that takes advantage of state-of-the-art tools in catalytic DNA biology, catalytic molecular beacons biotechnology and nanoparticle nanotechnology. Catalytic DNA molecules specific for heavy metal ions will be obtained through in vitro selection, and converted to fluorescent (for quantitative measurement) and colorimetric (for qualitative and semi-quantitative measurement) sensors by combining the DNA with fluorophore/quencher pairs and gold nanoparticles, respectively. The feasibility of transforming the innovations into commercial success at the DzymeTech has been established in the NIH STTR Phase I project (1R41ES014125-01), in which catalytic DNA sensors for lead(II) and uranium(VI) have been obtained that have high sensitivity (e.g., ~ 11 ppt) and selectivity (e.g., > 1 million fold). This Phase II application addresses critical issues of transferring the sensor design into prototypes of sensor kits for markets. The customer requirements will be determined and prototype components and protocols will be developed. They include: "Obtain all four fluorescent and colorimetric sensors for Pb(II), U(VI), Cd(II), and Hg(II). Characterize the sensors by determining the detection limit and selectivity of each sensor. "Design and characterize prototype sensor kits for each metal ion. Including sensor components, storage condition and test protocol optimization, high/low temperature stability tests and reproducibility tests with sensors from multiple-batches. "Test field samples to study interference and matrix effects. Real field samples, including soil and water samples will be collected and tested. Sensor performance with real samples will be used to evaluate the commercialization values of the sensor kits.

Public Health Relevance:
Highly sensitive and selective catalytic DNA sensors for lead(II), uranium(VI), cadmium(II), and mercury(II) will be developed for cost-effective on-site and real-time detection and quantification. Heavy metal ions are widely present in the environment, causing significant health problems such as damages to brain, kidney, and neural system to human beings, especially children. Convenient portable sensors developed in this project will enable government inspectors, environmental monitors, household users, clinicians and first-responders make informed decision about remediation and monitoring strategy and thus improve human health and quality of life.

Public Health Relevance:
This Public Health Relevance is not available.

Thesaurus Terms:
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