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Nanopore-based multi-target analysis of Zika virus infection

基于纳米孔的寨卡病毒感染多靶点分析

基本信息

批准号：
10395953
负责人：
Holger Schmidt
金额：
$ 56.71万
依托单位：
UNIVERSITY OF CALIFORNIA SANTA CRUZ
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10395953
关键词：
Animal Model Attention Biological Markers Callithrix Clinical Complex Detection Diagnostic Disease Electrostatics Fluorescence Foundations Genomics Goals Growth Label Left Liquid substance Membrane Microfluidic Microchips Microfluidics Microspheres Molecular Molecular Analysis Molecular Diagnostic Techniques Molecular Target Nucleic Acids Nucleic acid sequencing Optics Outcome Phase Preparation Principal Investigator Proteins Proteomics Radial Research Research Technics Saliva Sampling Seminal fluid Serum Solid Specificity Stream System Systems Integration Technology Time Urine Validation Work ZIKA ZIKV infection base clinical biomarkers clinically relevant detection assay detection limit disease diagnostic fundamental research high throughput analysis innovation molecular diagnostics molecular marker nanopore next generation next generation sequencing novel novel strategies optical traps particle personalized medicine programs protein biomarkers quantum real world application single molecule small molecule specific biomarkers targeted delivery waveguide

项目摘要

Principal Investigator/Program Director: Schmidt, Holger Project Summary Spurred by the explosive growth in personalized medicine which requires highly sensitive genomic and proteomic analysis, single molecule detection is rapidly developing from a fundamental research technique into the foundation for advanced molecular diagnostic techniques. Whereas optical fluorescence detection used to be the approach of choice, electrical detection of single molecules as they are drawn through a nanopore has recently gained great attention, particularly in the context of next generation sequencing. The direct, label-free detection of a wide range of molecules using nanopores has much broader potential. However, a major obstacle for fully exploiting the exquisite sensitivity of nanopore detection is the mismatch between the minute electrostatic capture volume of a nanopore and the low concentrations encountered in real-world applications, e.g. in molecular diagnostics. The goal of this project is to overcome this limitation with a novel, innovative approach to high- throughput molecular diagnostics using single molecule nanopore analysis. The specific objectives of this application are to increase the capture rate (throughput) of a nanopore by orders of magnitude and to validate this approach with clinical samples for Zika virus (ZIKV) infection. Our central hypothesis is that this can be accomplished by delivering target molecules isolated on microbeads within the capture radius of the pore using a chip-based optical trap on a waveguide-based optofluidic chip. The objectives of this application will be accomplished by the following Specific Aims: (1) Nanopore capture rate enhancement using optical trapping of carrier beads. This Aim will validate the core of our new approach and demonstrate a 50,000x improvement for both nucleic acids and proteins; (2) On-chip integration of microfluidic sample processing with high throughput molecular detection at ultralow (attomolar) concentrations; and (3) Multiplex direct detection of ZIKV infection starting from complex sample matrices (serum, saliva, urine, semen). The innovative contributions of the proposed work are: (i) Optical trapping of carrier particles for molecular target delivery; (ii) Creating an integrated chip-based system for nanopore-based, label-free detection of diverse molecular biomarkers; and (iii) Clinical validation of nanopore- based analysis of multiple analyte types. The proposed work is significant because it will introduce the first integrated system that matches the sensitivity, simplicity, and versatility of single-molecule nanopore detection with the real-world constraints for molecular diagnostics. As such, this approach will be applicable to many molecular targets and applications. 1

首席研究员/项目主任：Schmidt， Holger

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Recent advances in integrated solid-state nanopore sensors.

DOI：
10.1039/d1lc00294e
发表时间：
2021-08-21
期刊：
Lab on a chip
影响因子：
6.1
作者：
Rahman M;Sampad MJN;Hawkins A;Schmidt H
通讯作者：
Schmidt H

Optical trapping assisted detection rate enhancement of single molecules on a nanopore optofluidic chip.

DOI：
10.1364/optica.6.001130
发表时间：
2019-09-20
期刊：
Optica
影响因子：
10.4
作者：
Rahman M;Harrington M;Stott MA;Li Y;Sampad MJN;Yuzvinsky TD;Hawkins AR;Schmidt H
通讯作者：
Schmidt H

Optical trapping assisted label-free and amplification-free detection of SARS-CoV-2 RNAs with an optofluidic nanopore sensor.

DOI：
10.1016/j.bios.2021.113588
发表时间：
2021-12-15
期刊：
Biosensors & bioelectronics
影响因子：
12.6
作者：
Sampad MJN;Zhang H;Yuzvinsky TD;Stott MA;Hawkins AR;Schmidt H
通讯作者：
Schmidt H

Nano/microfluidic device for high-throughput passive trapping of nanoparticles.

DOI：
10.1063/5.0176323
发表时间：
2023-11
期刊：
Biomicrofluidics
影响因子：
3.2
作者：
Tanner Wells;Holger Schmidt;Aaron Hawkins
通讯作者：
Tanner Wells;Holger Schmidt;Aaron Hawkins

Free-Space Excitation of Optofluidic Devices for Pattern-Based Single Particle Detection.

DOI：
10.1109/lpt.2021.3069673
发表时间：
2021-08-15
期刊：
IEEE photonics technology letters : a publication of the IEEE Laser and Electro-optics Society
影响因子：
0
作者：
Amin MN;Ganjalizadeh V;Hamblin M;Hawkins AR;Schmidt H
通讯作者：
Schmidt H