Integrated Nano-Opto-Fluidic System on Sapphire towards Single-Molecule Protein Sequencing
蓝宝石上的集成纳米光流控系统用于单分子蛋白质测序
基本信息
- 批准号:10473301
- 负责人:
- 金额:$ 133.95万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-01 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAmino Acid SequenceAmino AcidsBiologyCellsClassificationComplexDNA-Protein InteractionDetectionDevelopmentDevice DesignsDevicesDiagnosticElectric CapacitanceFaceFutureGenesGenome MappingsGenomicsGenotypeHeterogeneityIndividualKnowledgeLiquid substanceMasksMass Spectrum AnalysisMeasurementMedicineMethodsMicroscopyNanostructuresNoiseNucleic acid sequencingOpticsPeptide Sequence DeterminationPeptidesPolymerase Chain ReactionProtein FingerprintsProteinsProteomicsResearchSapphireSignal TransductionSpeedStructureSystemTechnologyTherapeuticbaseclinical applicationcostdeep learning algorithmdesignfluorescence microscopeimprovedintegrated circuitmethod developmentmultiple omicsnanonanofabricationnanophotonicnanoporenext generationportabilitysensorsingle moleculetranscriptomicswaveguide
项目摘要
PROJECT SUMMARY/ ABSTRACT
Enabled by the development of high-throughput, low-cost nucleic acids sequencing technologies, there have
been accelerated development in genomics and transcriptomics in the past two decades, profoundly reshaping
our knowledge in biology and medicine. However, similar technologies have yet to emerge for rapid identification
and quantification of proteins. This is attributed to more complex structures of proteins, lack of polymerase chain
reaction-like amplification methods, cellular heterogeneity, etc. Conventional protein sequencing methods, such
as Edman degradation and mass spectrometry, are slow, expensive, and not suitable for detecting low-
abundance proteins. Such ensemble measurements also can mask our fundamental understandings on how
cells of a particular genotype function and respond to therapeutics. Single-molecule protein sequencing (SMPS)
is an emerging research direction that directly reads amino acids sequence from individual protein or peptide
molecules. Yet, a promising strategy using fluorosequencing still relies on long Edman degradation cycles and
bulky fluorescent microscopes, not ideal for fast and low-cost readout. Electronic SMPS technologies using
tunneling or nanopore sensors are emerging methods for development of portable and inexpensive sequencing
systems. However, they still face challenges in precise nanofabrication, structural instability, high electronic
noise, and inability in detection of all amino acids. To address the multi-faceted challenges in next-generation
SMPS, we will design an on-chip integrated, electronic system that incorporates nano-opto-fluidic structures to
transduce protein fingerprints into electronic signals at a high speed, a low cost and a small system foot-print.
Our platform features an all-sapphire nanopore (AlSaPore) fluidic device that has a small capacitance and a
greatly improved structural stability, and accordingly suited for high-speed, low-noise, high-throughput, electronic
detection. Further, an ultrathin nitride-based metasurface-integrated circuit (MIC) structure is created on the
AlSaPore to optically interrogate the fluorescently tagged single amino acids passing through the nanopore
without conventional fluorescent microscopy. Subsequently, the fluorescent tag signals are transmitted through
the waveguide and collected by on-chip integrated photodetectors. The optoelectronic channel (IA for amino acids
tags) and ionic current channel (IP for protein primary structure) will be synchronously recorded, classified by
deep learning algorithms, and used in combination to improve the protein sequencing accuracy. Supported by
well-established nitride-on-sapphire device design and manufacturing technology, our MIC-AlSaPore is a
scalable and compact platform that achieves single-molecule sensitivity with a potential to read out all 20 amino
acids. The development of MIC-AlSaPore platform will have far-reaching impact in biomedicine beyond protein
sequencing. It may be used for studying DNA-protein interactions at single-molecule levels, classification of
specific genes, genome mapping and de novo assembly. Additionally, it may inspire future multi-omic (genomic,
transcriptomic, and proteomic) diagnostic solutions with potential clinical applications.
项目摘要/摘要
由于高通量、低成本的核酸测序技术的发展,有
在过去的二十年里,基因组学和转录组学加速发展,深刻地重塑了
我们在生物学和医学方面的知识。然而,类似的技术还没有出现用于快速识别
和蛋白质的量化。这归因于蛋白质的结构更加复杂,缺乏聚合酶链
类反应扩增方法、细胞异质性等。传统的蛋白质测序方法,如
由于埃德曼降解法和质谱仪,速度慢,价格昂贵,不适合检测低浓度的
丰富的蛋白质。这样的整体测量也掩盖了我们对如何
特定基因类型的细胞功能正常,并对疗法有反应。单分子蛋白质测序(SMPS)
是一个新兴的研究方向,直接从单个蛋白质或多肽中读取氨基酸序列
分子。然而,使用荧光测序的有希望的策略仍然依赖于长的埃德曼降解周期和
笨重的荧光显微镜,不是快速和低成本读出的理想选择。使用电子开关电源技术
隧道或纳米孔传感器是开发便携和廉价测序的新兴方法
系统。然而,它们在精密纳米制造、结构不稳定性、高电子性等方面仍面临挑战。
噪音,以及无法检测到所有氨基酸。应对下一代网络的多方面挑战
SMPS,我们将设计一种芯片上集成的电子系统,它结合了纳米光学流体结构,以
将蛋白质指纹转换成电子信号,速度快,成本低,系统占用空间小。
我们的平台采用全蓝宝石纳米孔(AlSaPore)流体器件,具有小电容和
极大地提高了结构稳定性,因此适用于高速、低噪声、高通量、电子化
侦测。此外,超薄氮化物基亚表面集成电路(MIC)结构被创建在
AlSaPore光学询问通过纳米孔的带有荧光标记的单一氨基酸
没有传统的荧光显微镜。随后,荧光标签信号通过
通过片上集成光电探测器收集到的光和光信号。氨基酸的光电子通道(IA
标签)和离子电流通道(用于蛋白质一级结构的IP)将被同步记录,并按
深度学习算法,并结合使用提高了蛋白质测序的准确性。支持:
成熟的蓝宝石氮化物器件设计和制造技术,我们的MIC-AlSaPore是一款
可扩展和紧凑的平台,可实现单分子灵敏度,并有可能读出所有20个氨基酸
酸。MIC-AlSaPore平台的开发将对蛋白质以外的生物医学产生深远的影响
测序。它可用于在单分子水平上研究DNA-蛋白质相互作用,分类
特定基因、基因组图谱和从头组装。此外,它可能会激发未来的多基因组(基因组,
转录学和蛋白质组学)具有潜在临床应用的诊断解决方案。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Chao Wang其他文献
Chao Wang的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Chao Wang', 18)}}的其他基金
High-Throughput, Rapid, and Epitope-Specific Quantification of Neutralizing Antibodies Using Digital Nanoparticle Sensors
使用数字纳米颗粒传感器对中和抗体进行高通量、快速和表位特异性定量
- 批准号:
10432809 - 财政年份:2022
- 资助金额:
$ 133.95万 - 项目类别:
High-Throughput, Rapid, and Epitope-Specific Quantification of Neutralizing Antibodies Using Digital Nanoparticle Sensors
使用数字纳米颗粒传感器对中和抗体进行高通量、快速和表位特异性定量
- 批准号:
10611462 - 财政年份:2022
- 资助金额:
$ 133.95万 - 项目类别:
相似海外基金
Cerebral infarction treatment strategy using collagen-like "triple helix peptide" containing functional amino acid sequence
含功能氨基酸序列的类胶原“三螺旋肽”治疗脑梗塞策略
- 批准号:
23K06972 - 财政年份:2023
- 资助金额:
$ 133.95万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Establishment of a screening method for functional microproteins independent of amino acid sequence conservation
不依赖氨基酸序列保守性的功能性微生物蛋白筛选方法的建立
- 批准号:
23KJ0939 - 财政年份:2023
- 资助金额:
$ 133.95万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Effects of amino acid sequence and lipids on the structure and self-association of transmembrane helices
氨基酸序列和脂质对跨膜螺旋结构和自缔合的影响
- 批准号:
19K07013 - 财政年份:2019
- 资助金额:
$ 133.95万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Construction of electron-transfer amino acid sequence probe with an interaction for protein and cell
蛋白质与细胞相互作用的电子转移氨基酸序列探针的构建
- 批准号:
16K05820 - 财政年份:2016
- 资助金额:
$ 133.95万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of artificial antibody of anti-bitter taste receptor using random amino acid sequence library
利用随机氨基酸序列库开发抗苦味受体人工抗体
- 批准号:
16K08426 - 财政年份:2016
- 资助金额:
$ 133.95万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The aa15-17 amino acid sequence in the terminal protein domain of HBV polymerase as a viral factor affect-ing in vivo as well as in vitro replication activity of the virus.
HBV聚合酶末端蛋白结构域中的aa15-17氨基酸序列作为影响病毒体内和体外复制活性的病毒因子。
- 批准号:
25461010 - 财政年份:2013
- 资助金额:
$ 133.95万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Amino acid sequence analysis of fossil proteins using mass spectrometry
使用质谱法分析化石蛋白质的氨基酸序列
- 批准号:
23654177 - 财政年份:2011
- 资助金额:
$ 133.95万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Precise hybrid synthesis of glycoprotein through amino acid sequence-specific introduction of oligosaccharide followed by enzymatic transglycosylation reaction
通过氨基酸序列特异性引入寡糖,然后进行酶促糖基转移反应,精确杂合合成糖蛋白
- 批准号:
22550105 - 财政年份:2010
- 资助金额:
$ 133.95万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Estimating selection on amino-acid sequence polymorphisms in Drosophila
果蝇氨基酸序列多态性选择的估计
- 批准号:
NE/D00232X/1 - 财政年份:2006
- 资助金额:
$ 133.95万 - 项目类别:
Research Grant
Construction of a neural network for detecting novel domains from amino acid sequence information only
构建仅从氨基酸序列信息检测新结构域的神经网络
- 批准号:
16500189 - 财政年份:2004
- 资助金额:
$ 133.95万 - 项目类别:
Grant-in-Aid for Scientific Research (C)














{{item.name}}会员




