Portable Instrument For Assessing Zinc Deficiency In Children and The Elderly

描述(申请人提供)：我们将建造一种便携式仪器，用于快速、简单、非侵入性地评估膳食锌缺乏。我们建议的诊断测量可以在每个受试者只需2-3分钟的时间内完成，并从受试者的一个指甲上取下光谱读数。我们的产品将使用低能量、纳秒的激光脉冲通过产生“火花”(等离子体)来“询问”指甲表面，并将量化来自这种短暂的指甲等离子体的光发射(光谱线)。(我们首席调查人员已经多次在自己的指甲上做过这样的事情。微小的激光“砰”一声可以感觉到，但不会受伤，也不会留下任何痕迹。)我们如下所示，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，通过系统地沿着指甲从近端到远端移动血浆生成点，我们可以调查受试者最近3-4个月的锌营养历史。(其他营养素和毒素的测量，如铁、铜、铅或汞，可添加到我们生产线的未来产品中。我们正在使用的这种分析方法被称为“激光诱导击穿光谱”(LIBS)，它是我们过去所称的“原子发射光谱”的新变体。现代固态激光器、电荷耦合器件、光电二极管和集成电路使整个仪器可以缩小到图1所示的Kigre Libs产品的尺寸和外形尺寸。(注：我们在LIBS仪器图片中添加了典型脉搏血氧仪的第二张图片，以显示光纤将如何指向指甲。)完整的便携式LIBS仪器可以在商业上买到(例如，图1)，价格约为20-3万美元，它们可以在重量约10磅的1A-12V电池上运行数小时。因此，我们开发的仪器当然可以现场携带，很容易在学校、诊所、检查室、疗养院或流动的“健康博览会”单位使用。本发明的意义在于，它将促进膳食缺锌的检测和知情补救。这种缺乏症影响着世界上约三分之一的人口，对幼儿的破坏性尤其大。目前的情况是，在2012年，诊断缺锌的唯一方法是抽取3-5毫升静脉血，在合适的采集管中离心，然后将样本送到ICPMS或AAS实验室进行仪器分析，这需要复杂而昂贵的程序。这意味着，即使是处于危险中的美国公民，通常也不会接受缺锌检测。缺锌在美国儿童中很普遍，特别是穷人和少数族裔，在市中心的非裔美国人和农村拉美裔青年中，缺锌率可达30%。由于缺锌导致的青少年身体和认知发育迟缓是广泛存在的，而且是可悲的。美国另一个面临风险的人群是老年人，其中各种糟糕的食物选择和行为导致多达一半的住院患者临床上缺锌。这种缺陷削弱了患者的免疫防御能力，并加剧了许多疾病。我们带来的创新是采用一种新颖的、基本上没有尝试过的解决方案来解决长期存在的临床问题。我们将发明所有的机械、电气和生物分析系统，以及允许卫生保健工作者在该领域使用LIBS的算法。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，以便对指甲锌进行准确的比率测量。为此，我们将在指甲剪下进行LIBS测定，然后用我们的参考方法-稳定同位素稀释电感耦合等离子体质谱(SSD-ICPMS)来测定同一剪下的锌。我们将反复调整和修改LIBS程序，直到我们可以复制稳定同位素稀释值。第二个要解决的问题将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，e将使用横向和纵向缺锌研究的受试者，将指甲的LIBS测量结果与基于血液的锌营养状况的“黄金标准”测量结果进行比较。

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.