Implantable microdevices with integrated optical imaging for high-throughput in situ tumor response and drug sensitivity measurement

具有集成光学成像的可植入微型设备，用于高通量原位肿瘤反应和药物敏感性测量

• 批准号: 10537990
• 负责人: Oliver Jonas
• 金额: $ 42.8万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-03-15 至 2024-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10537990
• 关键词: Adoption; Area; Biological; Biological Products; Biology; Chemicals; Clinical; Clinical Research; Clinical Trials; Data Set; Detection; Development; Devices; Disease; Disease Management; Documentation; Economics; Engineering; Ensure; Expenditure; Feedback; Functional Imaging; Future; Goals; Image; Immunologics; Immunology; In Situ; Intellectual Property; Joints; Label; Laboratories; Malignant Neoplasms; Measurement; Medical; Medicine; Metabolism; Modality; Molecular; Monitor; Optics; Output; Pathology; Patients; Pharmaceutical Preparations; Phenotype; Physiology; Play; Process; Quality Control; Raman Spectrum Analysis; Recording of previous events; Regimen; Reproducibility; Research; Research Personnel; Resistance; Response to stimulus physiology; Selection for Treatments; Signal Pathway; Speed; System; Technology; Testing; Therapeutic; Time; Tissues; Translational Research; Validation; cancer therapy; commercialization; cost effective; cytotoxic; design; detection method; drug sensitivity; human tissue; individual patient; industry partner; insight; instrument; metabolomics; microdevice; miniaturize; minimally invasive; molecular marker; novel; optical imaging; optimal treatments; personalized management; personalized therapeutic; pre-clinical; pre-clinical research; predicting response; product development; prototype; rational design; real time monitoring; response; sensor; side effect; small molecule; success; temporal measurement; transcriptomics; translational cancer research; translational medicine; tumor; tumor microenvironment

ABSTRACT: The ability to predict the optimal therapy for an individual patient is a major unmet need in the treatment of cancer and other diseases. The majority of therapies in clinical cancer treatment, particularly cytotoxics as well as combinations of multiple drugs, have no reliable predictor of response. This uninformed therapy selection is highly inefficient and likely leads to reduced therapeutic success rates, increased side effects and excessive economic expenditures. I develop novel “lab-in-a-patient” technology to probe, monitor, and eventually treat disease in real time within human tissue. A tiny, minimally invasive device will provide continuous output of information that reveals disease biology and informs treatment options. “Lab-in-a-patient” technology has the potential to act as a micro-pathology laboratory by allowing the real-time measurement of response to multiple therapies or other chemical perturbagens simultaneously within the patient. We have achieved proof-of-concept for release of microdoses of a large number of distinct drugs or molecular “sensors” in parallel into native tissue, with analysis of the effect for each such compound (Science Translational Medicine, 284ra57, 2015). We are augmenting this technology with miniaturized detection methods that enable optical in situ real-time monitoring of disease state and the effects of small molecules and biologics near each drug reservoir. This blend of high-throughput chemical perturbation and optical detection in a single instrument will, for the first time, enable diseased tissue to be monitored and functionally characterized in a continuous and noninvasive manner. It will thus provide unprecendented detail, precision and speed of analyzing response and resistance to therapeutics through live in situ readouts of signaling pathways, metabolites and other molecular markers. This approach may eventually push medicine away from trial-and-error treatments with longer-term macroscale endpoints and towards precision management of disease by probing, treating and monitoring locally at the microscale level. Use of the technology for local delivery of biological (non- therapeutic) probes into native tissue creates the capability for fundamental insights through direct stimulus-response measurements with real-time in situ monitoring, particularly in the areas of immunology, metabolism and cancer formation where the local tissue microenvironment plays a key role in the molecular processes underlying disease biology. In the fullness of time, these devices may enable individualized and real-time selection of optimal therapies and could facilitate rational design of more effective, personalized therapeutic regimens in numerous cancer indications. The proposed project spans continued technological and translational development that support eventual commercialization.

摘要：预测单个患者最佳疗法的能力是一个主要的未满足需求 在癌症和其他疾病的治疗中。临床癌症治疗中的大多数疗法， 特别是细胞毒素以及多种药物的组合，没有可靠的反应预测指标。 这种不知情的治疗选择效率很低，可能导致治疗成功降低 费率，副作用增加和超级经济支出。我开发了小说的“患者实验室” 在人体组织中实时探测，监测，有时监测甚至有时治疗疾病的技术。一个小的， 微创装置将提供揭示疾病生物学的信息的连续输出 并告知治疗选择。 “实验室”技术有可能通过允许使用的微分病理学实验室 简单地测量对多种疗法或其他化学扰动的反应 在患者内。我们已经实现了释放大量微量糖的概念证明 平行于天然组织的不同药物或分子“传感器”，并分析每个 这种化合物（科学转化医学，284RA57，2015）。我们正在用 微型检测方法，可以实现对疾病状态和疾病状态的原位实时监测 每个药物储层附近的小分子和生物制剂的影响。这种高通量的混合物 单个仪器中的化学扰动和光学检测将首次启用 患病的组织将在连续且无创的中受到监测和功能表征 方式。因此，它将提供前所未有的细节，分析响应和速度 通过现场读数信号通路，代谢物和其他的现场读数对治疗的抵抗力 分子标记。 这种方法最终可能会将药物从长期的试用和错误治疗中推动 宏观终点和通过探测，治疗和 在微观级别进行本地监视。使用该技术在本地传递生物学（非 - 对天然组织的治疗问题可以通过直接创造基本见解的能力 刺激反应测量通过实时原位监测，尤其是在 局部组织微环境的免疫学，代谢和癌症形成是关键的 在疾病生物学基础的分子过程中的作用。在时间里，这些设备可能 实现最佳疗法的个性化和实时选择，并可以主持合理设计 在许多癌症适应症中，更有效，个性化的治疗方案。拟议的项目 跨越技术和翻译开发，以支持事件商业化。