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Integration of Flexible Micro Spring Array and High Throughput Microfluidics for

柔性微弹簧阵列和高通量微流体的集成

基本信息

批准号：
8358451
负责人：
Siyang Zheng
金额：
$ 223.5万
依托单位：
PENNSYLVANIA STATE UNIVERSITY, THE
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-17 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8358451
关键词：
Accounting Antineoplastic Agents Biological Assay Biopsy Blood Blood Cells Blood Circulation Blood Volume Blood specimen Body part Cancer Patient Cancer Prognosis Cell Size Cells Cessation of life Clinic Detection Development Diagnosis Disseminated Malignant Neoplasm FDA approved Filtration Genetic Invaded Lead Leukocytes Liquid substance Malignant Neoplasms Mechanical Stress Methods Microfabrication Microfluidics Molecular Profiling Monitor Mutation Detection Neoplasm Metastasis Outcome Patient Isolation Patients Pharmaceutical Preparations Primary Neoplasm Process Reaction Risk Staging System Techniques Technology Testing Therapeutic Time Toxic effect Travel abstracting base cancer diagnosis cancer type chemotherapy clinically relevant cost cost effective drug efficacy efficacy testing experience flexibility improved minimally invasive neoplastic cell novel strategies pressure public health relevance treatment planning tumor progression

项目摘要

DESCRIPTION (Provided by the applicant) Abstract: The ability of metastatic cancer to release circulating tumor cells (CTCs) that travel through the blood and invade different parts of the body accounts for over 90% of cancer related deaths. New techniques for improved diagnosis and therapeutic strategies are desperately needed to improve patient outcomes in late stage metastatic cancer patients. One such technique involves the analysis of these CTCs through isolation from patient blood samples. Since molecular profiles of CTCs can be quite different from those of the primary tumor and more similar to the metastatic tumors, CTCs are better suited for metastatic cancer prognosis and diagnosis. Current CTC technologies have serious difficulties and limitations for clinic applications due to poor sensitivity and selectivity, high cost, and long processing times. CellSearchTM, the only current FDA approved system for CTC analysis, is only used for detection of CTCs and is not capable of preserving viable cells. The fundamental challenge with obtaining CTCs from blood samples is the fact that they are so rare, with only a few tumors cells occurring among billions of blood cells. Since tumor cells are almost always significantly larger than normal blood cells, size based separation has been demonstrated as an effective method for CTC capture. We have taken a novel approach to established microfiltration technology by implementing an array of flexible microsprings and using a regulated low pressure flow system to minimize the mechanical stresses experienced by cells during the filtration process. This is an efficient and cost effective system that is capable of the enrichment of viable CTCs from a clinically relevant blood volume of 7.5 mL in only 10 minutes. Despite achieving greater than 104 enrichment against leukocytes, the purity of the enriched cells is not sufficient for obtaining clinically relevant genetic information. We propose the incorporation of a high throughput microfluidic system that will physically partition these cells for analysis on a single cell level.By exploiting this inherent advantage of microtechnology, a large volume of parallel reactions can be used to overcome the issues with purity. Genetic expression profiles and mutation detections may be used for improved diagnosis, and lead to the development of highly personalized therapy plans that are optimized for each patient. Furthermore, the use of microfluidics for multiwell partitioning of CTCs will be used to attempt the establishment of favorable conditions for the culture of CTCs, even at an initially low seeding number. Successful primary culture of CTCs will allow drug efficacy tests that may be used to assay potential drugs ex vivo without exposing a patient to the unnecessary cost or toxic effects of chemotherapy. These new approaches based on the analysis of viable CTCs represent a different approach that has not been proven. However, since this technological platform is applicable to almost every type of cancer, it could fairly quickly revolutionize the way that therapies are derived for metastatic cancer patients. Public Health Relevance: The most deadly forms of cancer can release aggressive cells that circulate through the bloodstream and spread throughout the body. Microfabrication technology has been developed to effectively isolate these cells from a patient blood sample, allowing a minimally invasive "liquid biopsy" that may be performed often for monitoring tumor progression. This project explores the integration of a high throughput approach to analysis that will make it possible to test various anticancer drugs on these cells at no risk to the patient, and obtain genetic information that will be crucial to developing a highly personalized treatment plan.

描述（由申请人提供）