RAIL reduces variability and concentration of stress hormones in blood sampling

描述(由申请人提供)：在此第二阶段SBIR中，Actuated Medical，Inc.(F/k/a Piezo Resonance Innovation，Inc.)将完成共振辅助插入柳叶刀(RAIL)系统的开发，以减少实验动物血液采集期间的动物疼痛和应激反应。公共卫生问题：了解衰老的生理和生物学机制是许多研究的重点。纵向啮齿动物研究提供了对一般衰老过程和与年龄相关的主题(如营养、行为、免疫学、癌症和神经生物学)的重要见解。为了避免应激激素升高影响血液化学的问题，经常进行横断面研究。这些研究在每个时间点都需要许多动物，这不仅在动物使用和成本方面昂贵，而且限制了因果关系的研究。新的微扰血液采样策略是非常需要的，以实现在整个生命周期内进行连续血液采样。第一阶段成功开发了Alpha原型，达到了特定目标，并证明轨道装置将插入力降低了高达68%。用铁轨原型获得的血液样本皮质酮水平平均降低了60%。测量的平均方差减少了71%。由九(9)名动物研究科学家和兽医组成的焦点小组对这条铁路的反应非常积极。第二阶段将开发一种商业上可行的设备，在连续血液样本期间将动物压力降至最低，改善研究结果，并消除横断面研究的需要。第二阶段假设：在一项为期24个月的小鼠纵向重复抽样研究中，带轨道装置的振动静脉穿刺术将使血浆皮质酮水平降低60%？10%，与非振动静脉穿刺术相比，变异性降低60%？10%(p&lt；0.05)。第二阶段的具体目标：1.证明轨道装置可以减少小鼠的皮质酮释放，与以前在大鼠身上看到的相似。2.证明轨道装置广泛适用于降低在不同解剖位置采集的血液中的皮质酮水平。3.量化轨道装置在连续采血实验中的寿命优势(小鼠24个月的研究)。4.最终完成设备设计并生产60个单元，经过测试并准备上市。 公共卫生相关性：了解衰老的生理和生物机制以及激素在健康和异常衰老中所起的作用仍然是许多研究的重点。对啮齿动物模型中激素水平的研究对这一努力至关重要，但与传统血液采样技术相关的压力的影响是有问题的。人们迫切需要新的微扰采血策略，如即将在这里开发的设备，以支持在整个生命周期内进行连续血液采样，以更好地探索激素水平变化和衰老过程之间的联系，同时减少研究所需的动物数量。

DESCRIPTION (provided by applicant): In this Phase II SBIR, Actuated Medical, Inc. (f/k/a Piezo Resonance Innovations, Inc) will complete the development of the Resonance Assisted Insertion Lancet (RAIL") System to reduce animal pain and stress response during laboratory animal blood sampling. Public Health Problem: Understanding the physiological and biological mechanisms of aging is the focus of much research. Longitudinal rodent studies provide significant insights into the general aging process and age-related topics such as nutrition, behavior, immunology, cancer, and neurobiology. To avoid the problem of elevated stress hormones influencing blood chemistry, cross-sectional studies are often performed. These studies require many animals for each time-point, which is not only expensive in terms of animal use and cost, but limits the study of cause/effect relationships. New minimally-perturbing blood sampling strategies are highly desired to enable serial blood sampling over the lifespan. Phase I successfully developed Alpha prototypes, met the Specific Aims, and demonstrated that the RAIL device reduced insertion force by up to 68%. Blood samples obtained with the RAIL prototype had on average a 60% reduction in corticosterone level. The average variance in measurements was reduced by 71%. Response to the RAIL, from a focus group of nine (9) animal research scientists and veterinarians, was highly positive. Phase II will develop a commercially viable device that minimizes animal stress during serial blood samples, improving study results and eliminating the need for cross-sectional studies. Phase II Hypothesis: Vibrated venipuncture with RAIL device will reduce plasma corticosterone level by 60% ¿ 10% with decreased variability by 60% ¿ 10% compared to non-vibrated venipuncture in a 24-month longitudinal repeat sampling study in mice (p<0.05). Phase II Specific Aims: 1. Demonstrate that RAIL device offers similar reduction of corticosterone release in mice as that seen previously in rats. 2. Demonstrate widespread applicability of RAIL device to lower corticosterone levels in blood sampled at alternate anatomic locations. 3. Quantify the performance advantage of RAIL device in serial blood sampling experiment over the lifespan (24 Month Study in Mice). 4. Finalize device design and build 60 units, tested and ready for market release. PUBLIC HEALTH RELEVANCE: Understanding the physiological and biological mechanisms of aging and the role hormones play in healthy and abnormal aging continues to be the focus of much research. Studies of hormone levels in rodent models have been critical to this effort, but the effect of the stress associated with traditional blood sampling techniques is problematic. New minimally-perturbing blood sampling strategies, such as the device to be developed here, are highly desired to enable serial blood sampling over the lifespan to better explore links between changing hormone levels and the aging process, while reducing the number of animals required for the study.