Simple and Accessible Microfluidic Platform for Single Molecule Sequence Profiling of Tumor-derived DNA within Liquid Biopsies
简单易用的微流体平台,用于液体活检中肿瘤来源 DNA 的单分子序列分析
基本信息
- 批准号:10699214
- 负责人:
- 金额:$ 27.57万
- 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:2023-07-01 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdoptionAlgorithmsBar CodesBindingBiological AssayBiological MarkersBiopsyBloodBuffersCancer ControlCancer DetectionCancer DiagnosticsCancer PatientCause of DeathCessation of lifeClinicalClinical SensitivityColonoscopyColorColorectal CancerComplexCost AnalysisDNADNA MethylationDNA Sequence AlterationData AnalyticsDetectionDevelopmentDiagnosticDimensionsDiseaseDisease ProgressionEarly DiagnosisExpenditureFecesFluorescenceFormulationFrequenciesFutureGenesGenetic MaterialsGenomeGoalsHourImageImage AnalysisIndividualLaboratoriesLaboratory ResearchMachine LearningMalignant NeoplasmsMalignant neoplasm of cervix uteriMalignant neoplasm of lungMethodsMethylationMicrofluidicsModificationOpticsPap smearPatient CarePatient-Focused OutcomesPatientsPerformancePersonsPhasePlasmaPopulationProceduresReactionResearchResolutionResourcesSamplingSensitivity and SpecificitySiteSmall Business Innovation Research GrantSpecificitySystemTechniquesTechnologyThermodynamicsTimeTissuesTumor stageTumor-DerivedUninsuredUrineWorkbiomarker panelcancer biomarkerscancer typecell free DNAcirculating DNAclinical implementationclinically relevantcohortcostcost effectivedata analysis pipelinedesigndetection platformdigitaldigital platformdimensional analysisimagerimprovedinstrumentationliquid biopsymalignant breast neoplasmmanufacturemeltingmethylation biomarkermethylation patternminimally invasivemolecular markermortalitymultiplex assaynext generation sequencingnovel markerparallelizationpreventprototyperoutine screeningscreeningsingle moleculestandard of caretargeted biomarkertooltumor
项目摘要
Project Summary/ Abstract
Over 600,000 people in the US will die from cancer this year. It is estimated that 25% of these deaths could
have been prevented by detection in earlier stages. Implementation of minimally-invasive routine screening,
such as pap smears for cervical cancer, has proven to be an effective approach for reducing cancer mortality.
However, several challenges prevent successful implementation of screening in most cancers, especially ones
which are not readily accessible for imaging or tissue biopsy. One promising avenue for cancer diagnostics is
through use of circulating DNA from so-called “liquid biopsies” or other accessible sample media circulating
throughout the body collecting genetic material from tissues, including tumors. Tumor-specific molecular
biomarkers, such as DNA mutations and methylation, can be found in minimally-invasive sample media, such
as blood, stool, and urine, but are typically only present in very low copy numbers (<10 copies/mL) and low
fractions (<0.1%) among a high background of healthy DNA. Technical limitations as well as practical
inaccessibility of currently available tools have precluded research efforts to discover early-stage cancer-
specific DNA biomarker panels and subsequent clinical implementation that could improve patient outcomes.
To address this, we previously developed a prototype digital microfluidic platform to facilitate highly sensitive,
low-cost detection of cancer-specific DNA methylation patterns by highly parallelized single-molecule
thermodynamic sequencing. In this Phase 1 SBIR proposal, we will greatly expand upon the capabilities of this
platform to increase accessibility and improve analytical performance towards detection of early-stage disease
by significantly increasing its digitization power. We will develop a high-degree multiplexing paradigm for
detection and methylation profiling of biomarker panels using a multicolor barcoding technique. We will then
incorporate this assay into a microfluidic platform that can interrogate hundreds to thousands of single DNA
copies by digitizing template molecules into droplets for high-throughput single molecules analysis. The
platform will increase accessibility for biomarker research from liquid biopsies by reducing costs to <$25 per
sample and turnaround time to 4 hours. The platform will enable single-copy detection even among high
background populations (<0.001% sensitivity), which may be necessary for early-stage disease. The proposed
work in this Phase 1 project will develop the assay fundamentals for a multiplex, multidimensional analysis of a
clinically relevant biomarker panel (Aim 1), incorporate this assay into a highly-parallelized droplet microfluidic
platform (Aim 2), and assess its clinical feasibility with plasma samples from a cohort of lung cancer patients
and controls (Aim 3). This will lay the groundwork for a subsequent Phase 2 project to design the cartridge
and instrumentation for scalable manufacturing and user-friendliness and implement automated, machine-
learning image and data analysis pipelines.
项目摘要/摘要
项目成果
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