Droplet-based Spatially Encoded Live Cell Digital Extraction
基于液滴的空间编码活细胞数字提取
基本信息
- 批准号:10687620
- 负责人:
- 金额:$ 136.88万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-01 至 2026-08-31
- 项目状态:未结题
- 来源:
- 关键词:Alzheimer&aposs disease diagnosisBar CodesBehaviorBiological ProcessCancer BiologyCell membraneCellsCellular biologyDetectionDevelopmentDiagnosticDimensionsEarly DiagnosisGenotypeHeterogeneityImmunologyIndividualMeasuresMethodsMicrofluidicsMolecularMolecular AnalysisMonitorNanostructuresNanotechnologyNeurosciencesPathway interactionsPenetrationPhenotypePopulationSamplingStretchingStructureTechnologyTherapeuticTimebiological systemscytotoxicitydetection of nutrientdigitalindividual variationnanoscalenanowirenew technologynovel therapeuticsresponsesingle cell analysissingle moleculetool
项目摘要
Abstract
This proposal aims to develop a high throughput droplet-based digital subsampling tool that enables
continuous extraction of intracellular molecules (>1000 cells/sec) from individual living cells and achieve digital
single molecule detection. Technological advances in single cell analysis have resolved cellular heterogeneity
and enabled discovery of rare cell subpopulations. They have opened up new opportunities to detect subtle
molecular changes in the presence of variability in biological systems. Due to the uniqueness of individual cells
in their composition, functionality, and structures, molecular analyses at the single-cell level are critical for
understanding the complexity of biological processes and cellular responses to perturbations. To accurately
profile cellular dynamics and behaviors, it is essential to longitudinally monitor cellular changes and responses
over time. However, it has been challenging to acquire temporal molecular information from the same cell
populations due to the need of keeping them alive during the course of observation while minimizing their
perturbations.
Recently, nanotechnology methods (e.g. nanowire, nanobiopsy, nanostraw) have been developed for
longitudinal cell monitoring where nanoscale dimensions are used to penetrate cells and sample intracellular
molecules while providing minimal cytotoxicity. They have successfully achieved longitudinal cell subsampling
and analysis, but it has still been difficult to resolve inherent heterogeneity of individual cells and their contents
due to low throughput and sensitivity. In these studies, cells were placed on a substrate that consists of
different nanostructures and a scarce amount of molecules were extracted, limiting the ability to achieve high
throughput sampling and comprehensive downstream analysis. To build a robust longitudinal intracellular
extraction tool, there is a need to spatially barcode and profile individual cells at high throughput and measure
scant molecules with ultra-high sensitivity to maintain minimal perturbations during extraction.
Here, we propose a live cell digital subsampling technology that will combine a cell membrane perforator and
digital detection using droplet microfluidics to achieve i) live cell subsampling via hydrodynamic stretching of
individual living cells, ii) ultrasensitive digital profiling of individual molecules sampled from single cells, and iii)
monitoring of phenotypic and genotypic nutrient sensing pathway associated molecules for the early diagnosis
of Alzheimer's disease and the development of new therapeutics. We will advance this platform to better
understand cell biology and apply it to diverse fields including neuroscience, immunology, and cancer biology.
摘要
项目成果
期刊论文数量(0)
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{{ truncateString('JINA KO', 18)}}的其他基金
Mapping Single Extracellular Vesicles to Parent Cells for Immunotherapy Monitoring
将单个细胞外囊泡映射到亲本细胞以进行免疫治疗监测
- 批准号:
10569343 - 财政年份:2022
- 资助金额:
$ 136.88万 - 项目类别:
Mapping Single Extracellular Vesicles to Parent Cells for Immunotherapy Monitoring
将单个细胞外囊泡映射到亲本细胞以进行免疫治疗监测
- 批准号:
10633266 - 财政年份:2022
- 资助金额:
$ 136.88万 - 项目类别:














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