CAREER: ABO Blood Antigen Dielectrophoresis for Medical Diagnostics: Synergy with Desktop Experiment Modules (DEMos)

摘要CBET-0644538A。密西西比州立大学密尔里克目前，血液疾病的医学诊断依赖于昂贵而耗时的程序，这些程序被外包给特殊的分析实验室。新兴的电动微设备技术有可能用护理点设备取代离线实验室分析，这种设备可以在不到5分钟的时间内为患者提供阳性或阴性结果，以及关于疾病进展的定量信息。诊断疾病的一种方法是使用介电泳法(DEP)等工具来区分和量化异常和正常的血细胞。少数研究人员已经完成了血细胞的介电泳定性，但还没有人做过确定血型和其他固有生理特性的相关性的工作。这个项目的目的是研究血细胞在射频范围内(KHz到MHz)的介电反应，以纠正这一缺陷。这个职业计划的研究方面旨在1)通过实验量化所有八种血型(A+，B+，AB+，O+，A-，B-，AB-和O-)的反应，2)通过抗原修饰确定ABO抗原在介电极化中的作用，3)绘制血型膜不稳定和破裂的图，用于后续的亚细胞分析，以及4)用抗原电荷修改壳模型，以进一步了解细胞极化的机制。通过开发和传播针对不同教育水平的桌面实验模块(DEMO)，教育活动与研究活动交织在一起。具体地说，演示方法将用于1)吸引不同的学习方式，2)丰富包括运输和过程控制在内的课程，3)开发分析微设备技术的高级选修课，以及4)开发和实施外联活动，以吸引传统上代表较少的少数群体的学生学习科学、技术、工程和数学。智力优势：所有血型的基线数据的开发将引起学术界、医学界和工业界的智力兴趣。这八种血型的不同之处在于两种抗原和两种抗体的组合表达。PI的初步结果显示，不同血型之间的DEP反应存在差异。此外，红细胞是进一步了解分子包涵体如何改变细胞的有效极化率从而改变细胞电泳力的理想系统。这项工作还将开发基线数据，根据这些数据可以在未来的血液诊断设备中通过介电泳法区分异常细胞。最后，基于这些原理的演示将有助于从高中到研究生院学生的智力发展。广泛的影响：如果成功，拟议的研究将能够在不到五分钟的时间内，通过一滴血液最终确定感染/健康细胞的比率，这代表着医学诊断实践的一场革命。新技术的成果可能包括用于急性疾病或慢性病监测的便携式诊断设备，这两种设备都可以在偏远地区方便地使用，因为在那里无法进入传统的诊断实验室。将继续招收来自代表人数不足的少数群体的学生，并特别注意个性化辅导和留住学生。成功的研究和教育技术将广泛传播给学术界、医学界和工业界。

AbstractCBET-0644538A. Minerick, Mississippi State UniversityCurrently, the medical diagnosis of blood disorders rely on expensive and time consuming procedures that are outsourced to special analytical laboratories. Emerging electrokinetic microdevice technology has the potential to replace off-line lab analysis with point-of-care devices that could provide the patient with positive or negative results, along with quantitative information on disease progression, in less than 5 minutes. One way to diagnose disease is to use a tool such as dielectrophoresis (DEP) to distinguish and quantify abnormal versus normal blood cells. Dielectrophoretic characterization of blood cells has been performed by a handful of researchers, yet no work has been done to ascertain dependencies on blood type and other inherent physiological properties. The purpose of this project is to investigate the dielectrophoretic response of blood cells over the radio frequency range (kHz to MHz) to correct this deficiency.The research aspect of this CAREER program aims to 1) experimentally quantify the response of all eight blood types (A+, B+, AB+, O+, A-, B-, AB-, and O-), 2) definitively determine through antigen modification, the role of ABO antigens in dielectrophoretic polarization, 3) map out blood type membrane instabilities and rupturing for subsequent subcellular analysis, and 4) modify shell models with antigen charges to further understand the mechanics of cell polarizability. Educational activities are interwoven with research activities through the development and dissemination of Desktop Experiment Modules (DEMos) directed to a range of educational levels. Specifically, the DEMo approach will be used to 1) appeal to a variety of learning styles, 2) enrich courses including transport and process controls, 3) develop an advanced elective course in Analytical Microdevice Technology, and 4) develop and implement outreach activities to engage students of traditionally underrepresented minority groups in Science, Technology, Engineering and Math.Intellectual Merit: The development of baseline data for all blood types would be of intellectual interest to academic, medical, and industrial communities. The eight blood types differ by the expression of a combination of two antigens and two antibodies. Preliminary results by the PI show differences in DEP responses between blood types. In addition, red blood cells are an ideal system with which to further understand how inclusion of molecules can alter effective polarizability and thus dielectrophoretic force on a cell. This work will also develop baseline data from which abnormal cells can be dielectrophoretically distinguished in future blood diagnostic devices. Lastly, DEMos building on these principles will aid in the intellectual development of students from high school to graduate school.Broader Impacts: If successful, the proposed research would enable eventual determination of an infected / healthy cell ratio with a single drop of blood in under five minutes, representing a revolution in medical diagnostic practice. Outgrowths of the new technology might include portable diagnostic devices for acute diseases or monitoring of chronic diseases, both of which could be conveniently used in remote geographical areas, where traditional diagnostic laboratories are inaccessible. Students from underrepresented minority groups will continue to be recruited with particular attention given to personalized mentoring and retention. Successful research and educational techniques will be broadly disseminated to the academic, medical and industrial communities.