Portable Instrument For Assessing Zinc Deficiency In Children and The Elderly

描述（由申请人提供）：我们将制作一种便携式仪器，用于快速、简便、无创地评估膳食锌缺乏症。我们建议的诊断测量可以在每个受试者2-3分钟内完成，光谱读数从受试者的图1中取出。指甲。我们的产品将使用低能量、纳秒级的激光脉冲，通过产生“火花”（等离子体）来“询问”指甲表面，并将从短暂的指甲等离子体中量化光发射（光谱线）。(我们这些首席研究员已经在自己的指甲上做过很多次了。微小的激光“砰”一声可以感觉到，但不会造成伤害，也不会留下任何痕迹。)我们在下面展示，我们可以检测和定量锌（和其他元素）在指甲等离子体精确，比例测量解决方案。一个典型的指甲代表3-4个月的生长，通过沿着指甲系统地将血浆产生点从近端移动到远端，我们可以调查受试者最近3-4个月的锌营养史。(其他营养素和毒素的测量，如铁，铜，铅或汞可以添加到我们的产品线未来的产品。我们使用的这种分析方法被称为“激光诱导击穿光谱”（LIBS），它是我们过去称之为“原子发射光谱”的一种新变体。现代固态激光器、ccd、光电二极管和集成电路使整个仪器缩小到如图1所示的Kigre LIBS产品的尺寸和外形。（注：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，以显示我们的光纤是如何被引导到指甲上的。）完整的便携式LIBS仪器是市售的（例如，图1），价格约为20- 3万美元，它们可以在重约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在现场携带，很容易在学校、诊所、检查室、疗养院或移动“健康博览会”单位使用。本发明的意义在于，它将有助于检测和知情补救膳食锌缺乏症。这种缺乏症影响到世界上约三分之一的人口，对幼儿尤其具有破坏性。就目前的情况来看，在2012年，诊断缺锌的唯一方法是抽取3-5毫升静脉血，在合适的收集管中离心，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。这意味着即使是有患病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，尤其是穷人和少数民族，在市中心的非洲裔美国人和农村的西班牙裔青年中缺乏率可达30%。由于缺锌导致的青少年身体和认知发育迟缓是普遍的，而且是悲惨的。另一个面临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。这种缺乏削弱了病人的免疫防御，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一个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，以及算法，使LIBS能够被卫生保健工作者在现场使用。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，以便产生准确的指甲锌比例测量。为此，我们将对指甲屑进行LIBS测定，然后用我们的参考方法-稳定同位素稀释ICP质谱法测定同一指甲屑中的锌。我们将反复调整和修改我们的LIBS程序，直到我们可以重复稳定同位素稀释值。第二个要解决的问题将是阐明受试者指甲锌与他或她的锌营养状况之间的关系。为此，他将比较指甲的LIBS测量值与基于血液的锌营养状况的“金标准”测量值，使用来自横断面和纵向锌缺乏症研究的受试者。

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.