We will build a portable instrument for quick, easy, and non-invasive, assessment of dietary zinc deficiency. Our proposed diagnostic measurements can be done in just 2-3 minutes per subject, with spectroscopic readings taken off one of the subject's FIGURE 1. fingernails. Our product will use a low-energy, nanosecond, laser pulse to "interrogate" the fingernail surface by creating a "spark" (plasma) and will quantify the light emissions (spectral lines) from that brief fingernail plasma. (We principal investigators have done this on our own fingernails many times. The minuscule laser "pop" can be felt, but does not hurt and leaves no mark.) We show below that we can detect and quantitate zinc (and other elements) in the nail plasma for an accurate, ratiometric measurement solution. A typical fingernail represents 3-to-4 month's growth, and by systematically moving the point of plasma creation along the nail from proximal to distal, we can survey ~ 3-4 months of the subject's recent zinc nutritive history. (Measurement of other nutrients and toxins such as Fe, Cu, Pb or Hg can be added in future products in our line. This analytical method we are using is called "Laser-Induced Breakdown Spectroscopy" (LIBS), and it is a new variant of what we used to call "atomic emission spectroscopy." Modern solid-state lasers, CCDs, photodiodes, and ICs have allowed the entire instrument to be shrunk to the size and form-factor shown for the Kigre LIBS product in Figure1. (NOTE: We added to the LIBS instrument picture a second picture of a typical pulse oximeter to show how our optical fibers would be directed to the fingernail.) Complete, portable LIBS instruments are commercially available (e.g., Fig 1) for ~ $20-$30K, and they can be run for hours on 1A-12V battery weighing ~10 pounds. Thus, the instruments we develop can certainly be field-portable and easily used in schools, clinics, exam rooms, nursing homes, or mobile "health-Fair" units. The Significance of our invention is that it will facilitate detection and informed-remediation of dietary zinc deficiecy. Such deficiency affects about 1/3 of the world's population and is especially devastating to young children. As things stand now, in 2012, the only way to diagnose zinc deficiency is to draw 3-5 mL of venous blood, centrifuge it in a suitable collection tube, then send the sample to an ICPMS or AAS laboratory for instrumental analysis requiring complex and expensive procedures. This means that even US citizens at risk are generally not tested for zinc deficiency. Zinc deficiency is widespread among American children, especially the poor and minorities, where deficiency rates can reach 30% among inner city African American and rural Hispanic youth. The stunting of physical and cognitive development of the young from zinc deficiency is wide-spread, and tragic. The other US population at risk is the elderly, among whom various poor food choices and behaviors lead as many as half of those admitted to hospital to be clinically zinc deficient. Such deficiency weakens the immune defenses of patients and exacerbates numerous ailments. The innovation we bring is to adapt a novel and essentially untried solution to a long-standing clinical problem. We will be inventing all of the mechanical, electrical, and bio-analytical systems, and algorithms that will allow LIBS to be used in the field by health care workers. There are two main problems that we must solve. First, the raw intensity of the zinc atomic emissions must be combined with emission intensities from other fingernail elements in order to generate an accurate, ratiometric measurement of fingernail zinc. For this, we will do LIBS determinations on nail clippings, then measure the zinc in the same clippings by our reference method, which is stable-isotope-dilution ICP mass spectrometry. We will iteratively adjust and modify our LIBS procedures until we can duplicate the stable-isotope dilution values. The second problem to solve will be the elucidation of the relationship between a subject's fingernail zinc and his or her zinc nutritional status. For that, e will compare LIBS measurements from fingernails with the blood-based "gold standard" measurements of zinc nutritional status, using subjects from both a cross-sectional and a longitudinal zinc-deficiency study.

Public Health Relevance

The present project has emerged from decades long discussions among clinicians who study zinc nutrition and those who work primarily on zinc measurement and zinc imaging technologies. Briefly, the clinicians have been asking, isn't there some quick and easy way to measure a person's zinc status as we can measure glucose, cholesterol, or even cancer or allergen antibodies in a drop of blood ? Until now, the answer was always, No, you must draw a few mL's of blood, prepare the sample, and send it to an analytical laboratory. This lack of a rapid, inexpensive point-of-care test for zinc is particulaly distressing when it is realized that we have known about zinc's nutritional roles and the devastating effects of zinc deficiency for over 50 years. In the last decade, several agencies such as the World Health Organization, USAID, and the Gates Foundation have all announced initiatives to treat zinc deficiency both in the US and world-wide. In 2008, the Copenhagen Consensus, a Multi-National Non-Government Group that includes 7 Nobel laureates, declared Zinc Supplementation (jointly with vitamin A supplementation) the number-one most cost-effective approach to improving health world-wide. ://www.unitedcalltoaction.org/ documents/Investing _in_the_future_Summary.pdf;Horton et al., 2009). Despite all of the attention on zinc nutriture, we still lack a key tool, namely, a fast, simple, cheap, and reliable way to determine a person's zinc status. We believe that our LIBS analysis of fingernails can fill that need. Simply giving extra zinc to everyone might be simpler however, it seems apparent that clinicians in most situations would prefer to measure zinc status diagnostically and during remediation. Treating patients without being able to assure that zinc levels are adequate to avoid death from diarrhea caused by malnutrition or to monitor the zinc levels which influence the immune system is not optimal. We are optimistic that we can diagnose and measure zinc deficiency with our LIBS approach, but there are several, non-trivial technical challenges. First we must find the right methods to get accurate, reproducible determinations of the concentration of zinc in nails using the LIBS approach. Second, we must establish the relationship between fingernail zinc concentration and the other, gold standard measures of zinc nutriture status. Again, we are optimistic that the relationships are lawful and that the nail measure is a good proxy for other measurements of zinc nutriture status;but we are not yet certain. If we are right, and the nail measurement can be used clinically, then the instrument can be used for research and clinical treatment practically anywhere in the world. Laser-based instruments like this are routinely ruggedized for even military field use, with battery power. Finally, the business model we anticipate will be like prepaid cell phones. We expect that government and NGO agencies (Gates, UNICEF, WHO) will be the early adopters, with research teams next, and health care providers joining later. We will either lease or loan the instruments to users, and the instrumen will be pre- loaded with, say, 1000 measurement counts loaded into memory. Once they have used their counts, the user will log onto an internet site, give a credit card number, and receive by email a new code to another set of counts. In that way, the capital cost of the instruments can be deferred or financed by third parties, and the instruments can be upgraded as needed, while the customers only pay-as-they-go. Per-measurement costs will be set by economic factors. In the present Phase I project we will (i) perfect our fingernail analytical methods for criterion performance and (ii) undertake two small clinical trials with the instrument. These latte clinical trials will show whether or not fingernail zinc is promising as a clinically-useful measur of zinc nutritional status. We believe that at least these preliminary clinical data are necessary o guide and inform a GO:NO-GO decision for Phase II and an eventual product.

Agency
National Institute of Health (NIH)
Institute
National Institute of Nursing Research (NINR)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43NR014102-01
Application #
8459167
Study Section
Special Emphasis Panel (ZRG1-SBIB-Q (11))
Program Officer
Cotton, Paul
Project Start
2013-07-01
Project End
2014-12-31
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
1
Fiscal Year
2013
Total Cost
$144,614
Indirect Cost
Name
Neurobiotex, Inc.
Department
Type
DUNS #
005395335
City
Galveston
State
TX
Country
United States
Zip Code
77550