Rapid Molecular Detection of PML/RARalpha

我们提出了一系列的实验，旨在开发快速检测两个最常见的PML-RAR α融合mRNA从哺乳动物细胞使用MEMS为基础的电化学传感器阵列。这些研究的最终目标是开发一种廉价、用户友好的系统，能够在不到一小时的时间内诊断90%的APL病例。这样的系统将有助于在最初表现的数小时内而不是数天内开始ATRA，从而降低危及生命的出血的风险。一旦该系统完成，该集成系统的最大好处将是更高的完全缓解率，更重要的是，由于早期诊断，APL患者的总生存率提高。此外，这种新技术有望在肿瘤学领域具有越来越大的潜在用途，其中驱动恶性疾病过程的分子改变正在继续被表征。也许与人类恶性肿瘤相关的最充分研究的分子改变是在>95%的慢性髓细胞性白血病（CML）患者的白血病细胞中发现的费城染色体，其导致BCR和ABL基因的融合。我们的目标是在这里开发的检测系统，预计将适合于快速诊断慢性粒细胞白血病，也许其他恶性肿瘤以及。癌基因或肿瘤抑制基因表达改变、易位和其他诱发性遗传改变的分子诊断将越来越多地用于癌症检测和治疗方案的选择。基于MEMS-0的手持式电化学阵列检测的速度、多功能性、便携性、易用性和成本是当前分子技术的显著优势。原型PML/RAR α传感器阵列的分析有效性将通过第一阶段的里程碑来展示。拟议的商业应用：GeneFluidics的生命科学/电化学实验室位于加利福尼亚州托兰斯市，这是加利福尼亚州洛杉矶的一个商业/工业区。这个位置距离UCLA有20分钟的路程，Irvin Chen博士和Neil Shah博士在那里有他们的办公室。我们的实验室占地一千平方英尺.为了研究和开发的目的，有4台台式电脑，3台笔记本电脑和完整的互联网接入和网络连接。我们的实验室有一个加工和电子原型的部分。一个隔离室是为“脏”加工而建的，这个房间是加压的，所以它不会污染隔离室外面的实验装置。

We propose a series of experiments aimed to develop rapid detection of two most common PML-RARalpha fusion mRNAs from mammalian cells using MEMS-based electrochemical sensor array. The ultimate goal of the studies is the development of an inexpensive, user-friendly system capable of diagnosing 90 percent of APL cases in less than one hour. Such a system would facilitate initiation of ATRA within hours, instead of days, of initial presentation, and thereby reduce the risk of life- threatening hemorrhage. Once the system is completed the greatest benefits of this integrated system will be higher complete remission rates, and more importantly, improved overall survival of patients with APL due to earlier diagnosis. Furthermore, this novel technology promises to be of growing potential use to the field of oncology, where the molecular alterations which drive malignant diseases processes are continuing to be characterized. Perhaps the most well-studied molecular alteration associated with human malignancy is the Philadelphia chromosome found in the leukemic cells of >95% of patients with chronic myelogenous leukemia (CML), which results in the fusion of BCR and ABL genes. The detection system we aim to develop here is expected to be made amenable to the rapid diagnosis of CML and perhaps other malignancies as well. Molecular diagnosis of alterations in oncogene or tumor suppressor gene expression, translocations, and others predisposing genetic alterations will increasingly be used for cancer detection and choice of therapeutic options. The speed, versatility, portability, ease of use and cost of the handheld MEMS- 0based electrochemical array detection are significant advantages over current molecular technologies. The analytical validity of a prototype PML/RARalpha sensor array will be shown through milestones in Phase I. PROPOSED COMMERCIAL APPLICATIONS: GeneFluidics' Life Science/Electrochemistry Laboratory is located in Torrance, CA, a business/industrial area of Los Angeles, CA. This location is 20 minutes from UCLA where Dr. Irvin Chen and Dr. Neil Shah have their office. Our laboratory occupies 1,000 square feet. For research and development purposes, there are 4 desktop computers, 3 laptop computers and complete internet access and network connection. Our laboratory has a section for machining and electronics prototyping. An isolation room is built for "dirty" machining and the room is pressurized so it won't contaminate the experiment setup outside the isolation room.