Portable Instrument For Assessing Zinc Deficiency In Children and The Elderly

用于评估儿童和老年人缺锌的便携式仪器

• 批准号: 8459167
• 负责人: CHRISTOPHER J. FREDERICKSON
• 金额: $ 14.46万
• 依托单位: NEUROBIOTEX, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8459167
• 关键词: Affect; African American; Agreement; Air; Algorithms; Allergens; American; Antibodies; Attention; Bedside Testings; Blood; Blood Chemical Analysis; Budgets; Businesses; Capital; Carbon; Cellular Phone; Cessation of life; Child; Choice Behavior; Cholesterol; Clinic; Clinical; Clinical Data; Clinical Research; Clinical Treatment; Clinical Trials; Clip; Code; Cognitive; Collection; Complex; Consensus; Data; Dental; Detection; Development; Diagnosis; Diagnostic; Diarrhea; Dietary Zinc; Distal; Distress; Documentation; Drops; Dust; Dyes; Economic Factors; Elderly; Electronic Mail; Elements; Figs - dietary; Food; Foundations; Future; Generations; Glucose; Goals; Gold; Government; Growth; Health Fairs; Health Personnel; Hispanics; Hospitals; Hour; Household; Imaging technology; Immune; Immune system; In Situ; Indium; Individual; Internet; Isotopes; Keratin; Laboratories; Lasers; Lead; Light; Liquid substance; Longitudinal Studies; Malignant Neoplasms; Malnutrition; Marketing; Mass Spectrum Analysis; Measurement; Measures; Mechanics; Memory; Methods; Military Personnel; Minority; Modeling; Monitor; Nail plate; Nitrogen; Noble Gases; Nursing Homes; Nutrient; Nutritional; Nutritional status; Optics; Paint; Patients; Performance; Persons; Phase; Physiologic pulse; Plasma; Polymers; Population; Populations at Risk; Principal Investigator; Procedures; Proteins; Proxy; Reading; Recording of previous events; Research; Residual state; Risk; Role; Running; Rural; Sampling; Schools; Scientist; Site; Small Business Innovation Research Grant; Solutions; Spectrum Analysis; Structure of nail of finger; Supplementation; Surface; Surveys; System; Testing; Time; Toxin; Tube; UNICEF; USAID; Variant; Venous; Vitamin A; Water; Work; World Health; World Health Organization; Youth; Zinc; Zinc deficiency; absorption; analytical method; base; cost; cost effective; emission spectroscopy; improved; inner city; innovation; instrument; light emission; nanosecond; novel; nutrition; operation; optical fiber; public health relevance; purge; ratiometric; remediation; solid state; stable isotope; standard measure; tool

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：我们将建立一个便携式仪器，用于快速，简单，非侵入性，评估膳食锌缺乏。我们提出的诊断测量可以在每个受试者的2-3分钟内完成，光谱读数取自受试者的图1。指甲。我们的产品将使用低能量纳秒激光脉冲，通过产生“火花”（等离子体）来“询问”指甲表面，并将量化来自短暂指甲等离子体的光发射（光谱线）。(We首席调查员已经在我们自己的指甲上做过很多次了。微小的激光“砰”的一声可以感觉到，但不会造成伤害，也不会留下任何痕迹。）我们在下文中显示，我们可以检测和定量指甲血浆中的锌（和其他元素），以获得准确的比率测量解决方案。 一个典型的指甲代表3-4个月的生长，并且通过系统地沿着指甲从近端到远端沿着移动等离子体产生点，我们可以调查受试者最近锌营养史的~ 3-4个月。（其他营养素和毒素的测量，如铁，铜，铅或汞可以添加在未来的产品在我们的线。 我们使用的这种分析方法被称为“激光诱导击穿光谱”（LIBS），它是我们过去称为“原子发射光谱”的新变体。“现代固态激光器、CCD、光电二极管和IC使整个仪器缩小到图1所示Kigre LIBS产品的尺寸和外形尺寸。(NOTE：我们在LIBS仪器图片中添加了第二张典型脉搏血氧仪的图片，以显示我们的光纤如何指向指甲。）完整的便携式LIBS仪器可商购获得（例如，图1）为约20 - 30 K美元，他们可以运行数小时的1A-12 V电池重量约10磅。因此，我们开发的仪器当然可以是现场便携式的，很容易在学校、诊所、检查室、疗养院或移动的“健康博览会”单位使用。 本发明的意义在于它将促进膳食锌缺乏的检测和信息补救。这种缺乏影响到世界人口的约三分之一，对幼儿的破坏性尤其严重。就目前情况而言，在2012年，诊断锌缺乏症的唯一方法是抽取3-5 mL静脉血，在合适的收集管中离心，然后将样品送到ICPMS或AAS实验室进行仪器分析，需要复杂而昂贵的程序。这意味着即使是有风险的美国公民通常也不会接受缺锌检测。锌缺乏症在美国儿童中很普遍，特别是穷人和少数民族，其中城市内的非洲裔美国人和农村西班牙裔青年的缺锌率可达30%。由于缺锌而导致的青少年身体和认知发育迟缓是广泛存在的，而且是悲剧性的。另一个有风险的美国人群是老年人，其中各种不良的食物选择和行为导致多达一半的住院患者临床缺锌。这种缺陷会削弱患者的免疫防御能力，并加剧许多疾病。 我们带来的创新是为一个长期存在的临床问题采用一种新颖的、基本上未经尝试的解决方案。我们将发明所有的机械，电气和生物分析系统，以及算法，使LIBS能够被卫生保健工作者用于该领域。我们必须解决两个主要问题。首先，锌原子发射的原始强度必须与其他指甲元素的发射强度相结合，以产生指甲锌的准确的比率测量。为此，我们将对指甲屑进行LIBS测定，然后通过我们的参考方法（稳定同位素稀释ICP质谱法）测量同一指甲屑中的锌。我们将反复调整和修改我们的LIBS程序，直到我们可以复制稳定同位素稀释值。要解决的第二个问题是阐明受试者的指甲锌与他或她的锌营养状况之间的关系。为此，我们将使用来自横断面和纵向缺锌研究的受试者，将指甲LIBS测量值与基于血液的锌营养状况“金标准”测量值进行比较。