Direct bioelectronic detection of SARS-CoV-2 from saliva using single-molecule field-effect transistor array
使用单分子场效应晶体管阵列直接生物电子检测唾液中的 SARS-CoV-2
基本信息
- 批准号:10320987
- 负责人:
- 金额:$ 44.78万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-12-21 至 2024-11-30
- 项目状态:已结题
- 来源:
- 关键词:2019-nCoVAddressBinding ProteinsBiological AssayBiological SciencesCOVID testCOVID-19 detectionCOVID-19 diagnosticCOVID-19 pandemicCOVID-19 testingCarbon NanotubesClinicalCommunicable DiseasesComplexDefectDetectionDevelopmentDevicesDiagnosisDiagnostic testsDifferential DiagnosisElectrolytesGoldHourImProvImmobilizationImmunoassayIndividualInfectionInfectious AgentInfluenzaKineticsLaboratoriesLlamaMembrane ProteinsNanotubesNew YorkNucleic Acid Amplification TestsNucleocapsid ProteinsOpticsPhasePolymerase Chain ReactionPopulation SurveillancePreparationProcessProteinsPublic HealthQuantitative Reverse Transcriptase PCRReaderReagentRecombinantsResearch PersonnelReverse TranscriptionSARS-CoV-2 transmissionSalivaSamplingSemiconductorsSensitivity and SpecificitySiteSmall Business Innovation Research GrantSpecificitySpecimenStructural ProteinSymptomsTechnologyTestingTimeTrainingTransistorsUniversitiesVaccinesViralViral Load resultViral ProteinsVirusantibody detectionantigen detectionantigen testbasebiobankbioelectronicscostdesigndiagnostic assayenv Gene Productsexperimental studyimprovedinnovationintegrated circuitmetal oxidemolecular arraymolecular diagnosticsmultiplex detectionnanobodiesparticlepathogenpoint of carepoint of care testingprogramsprotein structuresaliva samplesensorsingle moleculetemporal measurementtooltransmission processviral RNAviral detection
项目摘要
Direct bioelectronic detection of SARS-CoV-2 from saliva
using single-molecule field-effect transistor array
Nucleic acid tests have become the gold-standard for diagnostic testing for COVID-19, usually performed
in specialized laboratories. Most are based on reverse-transcription quantitative polymerase chain reaction
(qRT-PCR). The time required for specimen transport and processing results in a turnaround time that is typi-
cally several days. The few rapid (<1 hour) point-of-care (POC) tests are more expensive, still require sample
preparation and specialized reagents, and do not have the throughput needed for population surveillance. Di-
rect testing for the virus, which also reduces requirements for multiple reagents, is a necessary step to improv-
ing diagnostic testing. While four such antigen tests have been approved for detection of SARS-CoV-2 based
on immunoassays to the N protein, sensitivity is limited and no quantitation of viral load is possible.
We will address this gap by using DiagnostikosTM, an in-development rapid POC platform for direct, real-
time, multiplexed, quantitative bioelectronic detection of biomolecules that employs an all-electronic detection
device that functions at the single-molecule level. These single-molecule field-effect transistors (smFETs) are
arrayed on a complementary metal-oxide-semiconductor (CMOS) integrated circuit chip. Chips will interface
with an envisioned USB-stick-form-factor reader device. Robust single-domain antibodies, known as nanobod-
ies and immobilized on these devices, are used for sensitive detection of viral particles and viral debris. The
use of multiple nanobodies for a single protein and nanobodies for different proteins in a single assay allows
for significant improvements in specificity. Nanobodies will be specific for one or more of the four major struc-
tural proteins in SARS-CoV-2; the nucleocapsid (N) protein engulfing the viral RNA, the spike (S) protein, the
membrane (M) protein and the envelope (E) protein. No sample preparation or specialized reagents are re-
quired for detection, and the device will be designed to operate with saliva, which has very recently been
shown to be a reliable medium for detecting SARS-CoV-2. Individual sensor chips can be manufactured at a
cost of $35. With the addition of other nanobodies, these large dense arrays can also allow detection of many
pathogens in a single test.
In this Direct-To-Phase-2 SBIR program we will pursue several key innovations that are required to make
such a platform possible, including isolation of nanobodies for key structure proteins of SARS-CoV-2 (Specific
Aim 1), development of the smFET platform for antigen detection (Specific Aim 2), development of large
CMOS arrays of these smFET devices (Specific Aim 3), and verification of detection in increasingly complex
samples up to and including clinical samples (Specific Aim 4). This project is a partnership between university
researchers who developed the smFET technology and a venture-based start-up venture, Quicksilver Biosci-
ences, spun out to commercialize smFET technology and develop smFET/CMOS arrays for molecular diag-
nostic applications.
从唾液中直接对SARS-COV-2的直接生物电子检测
使用单分子现场效应晶体管阵列
核酸测试已成为Covid-19的诊断测试的金标准,通常进行
在专业实验室中。大多数基于反向转录定量聚合酶链反应
(QRT-PCR)。样品传输和处理所需的时间导致周转时间很典型
卡利几天。少数快速(<1小时)的即时(POC)测试更昂贵,仍然需要样品
准备和专业试剂,并且没有人口监视所需的吞吐量。 d
该病毒的RECT测试也减少了多种试剂的要求,是即兴即兴的必要步骤。
诊断测试。虽然已经批准了四项此类抗原测试以检测基于SARS-COV-2
在对N蛋白的免疫测定时,灵敏度是有限的,并且不可能定量病毒载量。
我们将通过使用Diagnostikostm来解决这一差距
使用全电子检测的生物分子的多路复用,定量的生物电子检测
在单分子级的功能的设备。这些单分子现场效应晶体管(SMFET)是
在互补的金属 - 氧化物 - 气门导体(CMOS)集成电路芯片上排列。芯片将接口
带有设想的USB粘合物读取器设备。强大的单域抗体,称为纳米型
IE并固定在这些设备上,用于对病毒颗粒和病毒碎屑的敏感检测。这
单个蛋白质和单个测定中不同蛋白质的单纳米生物剂用于单蛋白和纳米生物剂允许
以显着改善特异性。纳米生物的特定于四个主要结构中的一个或多个
SARS-COV-2中的Tural蛋白;吞噬病毒RNA的核蛋白质(N)蛋白,尖峰蛋白,
膜(M)蛋白和包膜(E)蛋白。没有样品制备或专门试剂是重新的
需要检测到的,该设备将被设计为使用唾液运作,而唾液最近一直是
显示为检测SARS-COV-2的可靠介质。单个传感器芯片可以在
费用为35美元。通过添加其他纳米体,这些较大的致密阵列也可以检测到许多
在一次测试中的病原体。
在这个直接到相关的SBIR计划中,我们将追求几项需要进行的关键创新
这样的平台可能,包括隔离SARS-COV-2的关键结构蛋白(特定的纳米构造)
目标1),开发用于抗原检测的SMFET平台(特定目标2),大型开发
这些SMFET设备的CMOS阵列(特定AIM 3),以及对越来越复杂的检测验证
样本直至临床样本(特定目标4)。这个项目是大学之间的伙伴关系
开发了SMFET技术和基于风险的初创企业的研究人员Quicksilver Biosci-
加密,旋转以商业化SMFET技术并开发用于分子诊断的SMFET/CMOS阵列
NOSTIC应用。
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)
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Kenneth L Shepard其他文献
Kenneth L Shepard的其他文献
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{{ truncateString('Kenneth L Shepard', 18)}}的其他基金
A Wireless micro-ECoG Prosthesis for Speech
用于语音的无线微型 ECoG 假肢
- 批准号:
10513407 - 财政年份:2021
- 资助金额:
$ 44.78万 - 项目类别:
A Wireless micro-ECoG Prosthesis for Speech
用于语音的无线微型 ECoG 假肢
- 批准号:
10490475 - 财政年份:2021
- 资助金额:
$ 44.78万 - 项目类别:
A Wireless micro-ECoG Prosthesis for Speech
用于语音的无线微型 ECoG 假肢
- 批准号:
10375951 - 财政年份:2021
- 资助金额:
$ 44.78万 - 项目类别:
A Wireless micro-ECoG Prosthesis for Speech
用于语音的无线微型 ECoG 假肢
- 批准号:
10706320 - 财政年份:2021
- 资助金额:
$ 44.78万 - 项目类别:
Direct bioelectronic detection of SARS-CoV-2 from saliva using single-molecule field-effect transistor array
使用单分子场效应晶体管阵列直接生物电子检测唾液中的 SARS-CoV-2
- 批准号:
10266395 - 财政年份:2020
- 资助金额:
$ 44.78万 - 项目类别:
Integrated, multiplexed high-frequency electronic analysis of DNA in nanopores
纳米孔中 DNA 的集成、多重高频电子分析
- 批准号:
8545205 - 财政年份:2012
- 资助金额:
$ 44.78万 - 项目类别:
Integrated, multiplexed high-frequency electronic analysis of DNA in nanopores
纳米孔中 DNA 的集成、多重高频电子分析
- 批准号:
8719765 - 财政年份:2012
- 资助金额:
$ 44.78万 - 项目类别:
Integrated, multiplexed high-frequency electronic analysis of DNA in nanopores
纳米孔中 DNA 的集成、多重高频电子分析
- 批准号:
8365334 - 财政年份:2012
- 资助金额:
$ 44.78万 - 项目类别:
Rapid Allergenic Particle Identification (RAPID)
快速过敏性颗粒识别 (RAPID)
- 批准号:
7337686 - 财政年份:2007
- 资助金额:
$ 44.78万 - 项目类别:
Rapid Allergenic Particle Identification (RAPID)
快速过敏性颗粒识别 (RAPID)
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8073325 - 财政年份:2007
- 资助金额:
$ 44.78万 - 项目类别:
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