Development of an Advanced Handheld Noninvasive Glucometer

描述（由申请人提供）：VivaScan打算通过向市场推出一种完全无创和无血的血糖仪来促进良好血糖控制的益处，该血糖仪将为糖尿病患者提供一种无痛的血糖测试方法。VivaScan开发了一种无创血糖监测仪，基于组织中近红外（NIR）光吸收的测量。我们的技术采用了一种获得专利的光桥（OB）方法，这是众所周知的惠斯通电桥的光学等效。OB测量样品在两个波长处的微分光吸收变化，以“消除”大的水和背景吸收，提供一个信号增强约1500数量级的“更清洁”的葡萄糖吸收信号。SBIR拨款和公司资金使VivaScan能够开发并成功测试VS191——一种先进的实验室原型手持式无创血糖监测仪。该设备采用光纤束来无创测量血糖。在持续约20秒的测量过程中，将手指放入仪器中，轻轻挤压，光线照射在指尖，其血液含量被调制，并测量和记录反射（后向散射）光。我们最近对10名志愿者的患者研究产生了450对数据，平均绝对预测误差为12%，100%的测量数据在克拉克误差网格的临床可接受的A和B区域（84%在120%的误差范围内）。与光纤束相关的四个因素限制了廉价、紧凑和坚固的手持无创血糖仪的发展。光纤束：1)透光效率低（~8%），测量信噪比低；2)价格昂贵（约1300美元）；3)设备内部需要较大（10 × 4厘米）的空间；4)需要一个精确的可移动的马车组件。这个第一阶段项目的目标是开发和测试一种没有光纤束的新设备的可行性，这种设备通过透射（后向散射）光学测量来无创地测定血糖。成功完成本提案的具体目标将导致设备提供更有效的操作，提高精度，显着降低制造成本和更紧凑的光产生/收集模块。拟议的SBIR第一期应用项目的目标包括：1)设计、制造和测试一个无纤维测量头；2)研制VS193无纤维手持式无创血糖监测仪；3)进行内部患者试验研究，以测试和验证VS193的性能。第二阶段的工作将开发和测试一种功能齐全、价格合理、无创的血糖仪。该装置对糖尿病患者的血糖控制质量有重大意义，但更重要的是，对他们的生活质量和寿命有重大意义。使用VivaScan设备优化血糖检测可以改善临床结果，并为个体患者和整个医疗保健系统节省大量成本。公共卫生相关性：糖尿病是一种痛苦的疾病，也是一个严重的公共卫生问题，影响着今天美国超过2080万人。NIH糖尿病控制和并发症试验提供了令人信服的证据，频繁的血糖监测（每天超过4次）和严格的血糖控制对糖尿病患者的长期健康有显著的好处[DCCT]。先前的研究表明，糖尿病患者平均每天只检测1.6次血糖（而不是首选的6-10次）。这表明，现有的侵入性手指棒血糖测量设备不能满足其目的。它们使用简单；然而，糖尿病患者不能常规使用它们，主要是因为手指棒测试是痛苦的，昂贵的，和混乱的。虽然这是一个迫切的需求，但目前还没有可用的消费设备可以无创地测量血糖。VivaScan正处于开发一种无创手持式血糖监测仪的后期阶段，该监测仪使用指尖反射（后向散射）的光进行测量。虽然取得的结果接近商业化精度，但我们遇到了阻碍我们进一步提高葡萄糖测量精度的问题。这是由于低检测光水平从手指透射测量系统降低了我们的信噪比。但是，我们已经确定了解决此问题的方法。第一期拨款申请详细介绍了我们如何通过引入一种新颖的光学测量方法来增加检测到的光线水平，以促进测量精度的提高。我们的最终目标是将我们的无创血糖监测仪推向市场。

DESCRIPTION (provided by applicant): VivaScan intends to promote the benefits of good glycemic control by bringing to market a completely noninvasive and bloodless, glucometer that will give people with diabetes a pain-free way to test their blood sugar. VivaScan has developed a noninvasive blood glucose monitor, based on measurements of near- infrared (NIR) light absorption in tissue. Our technology utilizes a patented Optical BridgeT (OB) method, which is the optical equivalent of the well-known electrical Wheatstone bridge. The OB measures the variation of differential optical absorption of the sample at two wavelengths to "null out" the large water and background absorption, providing a "cleaner" glucose absorption signal with a signal enhancement in the order of ~1500. SBIR grant and company funds have enabled VivaScan to develop and successfully test VS191 - an advanced laboratory prototype handheld noninvasive blood glucose monitor. The device employs a fiber optic bundle to noninvasively measure blood glucose. During a measurement that lasts ~20 seconds, the finger is placed into the instrument, gently squeezed, light is shone at the finger tip, its blood content modulated and the transflected (backscattered) light is measured and recorded. Our recent patient studies on 10 volunteers produced 450 data pairs with an average absolute prediction error of 12% and 100% of the measurement data in the clinically acceptable A and B zones of the Clarke error grid (84% within 120% error). Four factors associated with the fiber optic bundle limit the development of an affordable, compact and robust hand held noninvasive glucometer. The fiber optic bundle: 1) has a low light transmission efficiency (~8%) resulting in a low measurement signal to noise ratio; 2) is expensive (~$1300); 3) requires a large (10 x 4 cm) space inside the device; and 4) requires a precise movable carriage assembly. The objective of this Phase I project is to develop and test the feasibility of a new device without optical fiber bundles which noninvasively determines blood glucose by transflectance (backscattering) optical measurements. Successful completion of the specific aims for this proposal will result in a device that provides more efficient operation, improved accuracy, significantly less expensive manufacturing costs and a more compact light generation/collection module. The aims for the proposed SBIR Phase I Application project include: 1) Design, build and test a fiberless measurement head; 2) Build a VS193 fiberless handheld noninvasive blood glucose monitor; 3) Perform in-house patient pilot studies to test and validate the VS193 performance. The Phase II work would develop and test a fully functional compact, affordable, and noninvasive glucometer. The proposed device has dramatic implications for the quality of glucose control for diabetic persons, but more importantly, for their quality of life and longevity. Optimizing glucose testing with the VivaScan device can lead to improved clinical outcomes and substantial cost savings to the individual patient and to the entire health care system. PUBLIC HEALTH RELEVANCE: Diabetes is a miserable disease and a serious public health problem, affecting more than 20.8 million people in the United States today. The NIH Diabetes Control & Complications Trial provided compelling evidence that frequent blood-glucose monitoring (more than 4 times a day) and tight blood-glucose control offer significant benefits to the long-term health of a diabetic person [DCCT]. Previous studies show that on average, diabetic individuals test their glucose only 1.6 times a day (instead of the preferred 6-10 times). This is an indication that existing invasive finger stick glucose measuring devices do not serve their purpose. They are simple to use; however, diabetic individuals fail to use them routinely mainly because finger stick tests are painful, expensive, and messy. Although there is an urgent need, presently there is no available consumer device that can measure blood glucose noninvasively. VivaScan is in an advanced stage of developing a noninvasive handheld glucose monitor that uses measurements of the light transflected (backscattered) from the finger tip. Although the achieved results are nearing commercialization accuracy, we have encountered problems that are preventing us from further increasing the glucose measurement accuracy. This is due to the low detected light levels from the finger transflectance measurement system which reduces our signal to noise ratio. However, we have identified a means to resolve this issue. This Phase I grant proposal details how, by introducing a novel optical measurement method, we can increase the detected light levels in order to facilitate improvement of the measurement accuracy. Our ultimate goal is to bring our noninvasive blood glucose monitor to the market.