Rapid Label-Free Detection of Acute Promyelocytic Leukemia

急性早幼粒细胞白血病的快速无标记检测

• 批准号: 8322030
• 负责人: Lydia L Sohn
• 金额: $ 19.43万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-18 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8322030
• 关键词: Accident and Emergency department; Acute Myelocytic Leukemia; Acute Promyelocytic Leukemia; Acute leukemia; Address; Antibodies; Antigens; Arsenic Trioxide; Back; Blast Cell; Blood; California; Cell Line; Cell Size; Cell surface; Cells; Chicago; Clinical; Coagulation Process; Complete Blood Count; Computer software; Consultations; Detection; Detection of Minimal Residual Disease; Developing Countries; Device or Instrument Development; Devices; Diagnosis; Disease; Disease remission; Disseminated Intravascular Coagulation; Doctor of Medicine; Doctor of Philosophy; Emergency Situation; Equipment; Experimental Designs; Goals; Hand; Health Personnel; Home environment; Hospitals; Hour; Human; Human Cell Line; Human Resources; Immunophenotyping; Incidence; Individual; Institution; International; Label; Latin America; Lead; Leukemic Cell; Leukocytes; Life; Malignant - descriptor; Measures; Mechanics; Medical; Methods; Microfluidic Microchips; Microfluidics; Monitor; Newly Diagnosed; Organ; Outcome; Patients; Pharmaceutical Preparations; Physicians; Physicians' Offices; Preparation; Progranulocytes; Resistance; Sampling; Screening procedure; Shapes; Sorting - Cell Movement; Surface; System; Testing; Time; Training; Tretinoin; United States; United States National Institutes of Health; Universities; Whole Blood; base; clinical Diagnosis; clinically relevant; data acquisition; design; falls; innovation; leukemia; mortality; point of care; pre-clinical; technology development

DESCRIPTION (provided by applicant): We propose to develop a microfluidics device capable of detecting leukemic cells based on their cell- surface markers from patients with acute promyelocytic leukemia (APL). Approximately 7% of newly- diagnosed APL patients in the United States die within the first 48 hours, often of disseminated intravascular coagulation (DIC). In Latin America, where APL is the most frequent subtype of acute myeloid leukemia (AML), the mortality rate is significantly higher: 13% mortality within the first five days and an overall survival of about 50% [1]. This outcome is unfortunate, because it is preventable: if an APL diagnosis were made immediately when a patient first presents to a physician, then all-trans retinoic acid (ATRA) could be administered immediately. ATRA is life saving if given quickly to APL patients, because the incidence of DIC falls within hours of therapy. ATRA causes differentiation of APL cells and induces hematologic remissions initially on its own at a rate of >90%. Unfortunately, APL diagnosis requires expert hematopathologic review and careful immunophenotyping. When APL patients present late at night or on the weekends to their local doctor or emergency room (ER), they are often not diagnosed immediately, since hematologic consultation and clinical immunophenotyping are often unavailable then. Many hospitals do not even have the capability to make an acute leukemia diagnosis, due to insufficient hematopathologic expertise or lack of required equipment or trained technologists. Thus, many patients do not receive life-saving ATRA therapy right away. We propose to address this unfilled patient need with a point-of-care device capable of diagnosing APL, thereby allowing rapid initiation of appropriate therapy. Our device centers on-chip artificial pores that are functionalized with specific antibodies to screen, label- free, cells for size, shape, and specific cell-surface markers. The simple device allows true point-of-care, as it requires very little sample; virtually eliminates all sample preparation; has low-power requirements; and provides direct, accurate result in <5 minutes. Easily adaptable to a hand-held format, the results can display on a screen or be transmitted wirelessly to a physician's office (if performed at the patient's home) or hospital (if performed in a physician's office or local ER). Our device will perform complete blood counts and detect individual antigens important to immunophenotyping primary APL cells. The proposed two-year time line for device development is feasible given our current technology development and careful placement of milestones. Ultimately, our device could be adapted to many other clinical situations for rapid clinical monitoring. PI Lydia L. Sohn, Assoc. Prof. of Mechanical Eng. at the University of California, Berkeley will lead this NIH R21 project and fabricate/test the device. Co-PI Lucy A. Godley, M.D., Ph.D., and Assist. Prof. at The University of Chicago will provide interfacing among sample choice, experimental design, and clinical relevance. Senior Personnel, George Anwar, Ph.D. at UC Berkeley will lead in the software and hardware design and packaging of the device for point-of-care.

描述（由申请人提供）：我们提出开发一种能够基于急性早幼粒细胞白血病（APL）患者的白血病细胞的细胞表面标志物检测白血病细胞的微流体装置。在美国，大约7%的新诊断的APL患者在最初的48小时内死亡，通常死于弥散性血管内凝血（DIC）。在拉丁美洲，APL是急性髓细胞白血病（AML）最常见的亚型，死亡率显著较高：前五天内死亡率为13%，总生存率约为50% [1]。这种结果是不幸的，因为它是可以预防的：如果在患者首次就诊时立即诊断出APL，则可以立即给予全反式维甲酸（ATRA）。如果对APL患者迅速给予ATRA，则可以挽救生命，因为DIC的发生率在治疗后数小时内就会下降福尔斯。ATRA引起APL细胞的分化，并以> 90%的比率诱导最初的血液学缓解。 不幸的是，APL的诊断需要专家的血液病理学检查和仔细的免疫表型。当APL患者在深夜或周末出现在当地医生或急诊室（ER）时，他们通常不会立即被诊断出来，因为血液学咨询和临床免疫表型通常无法获得。许多医院甚至没有能力作出急性白血病诊断，由于血液病理学专业知识不足或缺乏所需的设备或训练有素的技术人员。因此，许多患者没有立即接受挽救生命的ATRA治疗。我们建议使用能够诊断APL的即时设备来满足这种未满足的患者需求，从而允许快速启动适当的治疗。 我们的设备集中在芯片上的人工孔，这些孔用特异性抗体功能化以筛选无标记的细胞的大小、形状和特异性细胞表面标记。简单的设备允许真正的护理点，因为它需要很少的样品;几乎消除了所有的样品制备;具有低功耗要求;并在5分钟内提供直接，准确的结果。易于适应手持格式，结果可以显示在屏幕上或无线传输到医生的办公室（如果在患者家中进行）或医院（如果在医生的办公室或当地ER进行）。我们的设备将进行全血细胞计数，并检测重要的免疫表型原APL细胞的个别抗原。考虑到我们目前的技术发展和精心安排的里程碑，拟议的两年时间表是可行的。最终，我们的设备可以适用于许多其他临床情况，以进行快速临床监测。 莉迪亚湖加州大学伯克利分校机械工程副教授Sohn将领导NIH R21项目并制造/测试该设备。共同PI露西A.戈德利医学博士，哲学博士、并协助。芝加哥大学的教授将提供样本选择、实验设计和临床相关性之间的接口。高级人事，乔治安瓦尔，博士在加州大学伯克利分校将导致在软件和硬件设计和包装的设备点的护理。

项目成果

Node-pore sensing enables label-free surface-marker profiling of single cells.

• DOI: 10.1021/ac504613b
• 发表时间: 2015-03-03
• 期刊: ANALYTICAL CHEMISTRY
• 影响因子: 7.4
• 作者: Balakrishnan, Karthik R.;Whang, Jeremy C.;Hwang, Richard;Hack, James H.;Godley, Lucy A.;Sohn, Lydia L.
• 通讯作者: Sohn, Lydia L.