Printed Electronic Biosensors for Point-of-Care Testing of Cardiovascular Biomarkers

用于心血管生物标志物即时检测的印刷电子生物传感器

• 批准号: 10599898
• 负责人: Aaron Franklin
• 金额: $ 51.22万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10599898
• 关键词: Acceleration; Acute; Ambulances; Angiopoietin-2; Antibodies; Binding; Biological; Biological Assay; Biological Markers; Biosensor; Blood; Brain natriuretic peptide; Carbon Nanotubes; Cardiac; Cardiovascular Diagnostic Techniques; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Charge; Chest Pain; Chronic; Clinic; Clinical; Clinical Management; Clinical Trials Database; Complex; Complication; Creatine Kinase; Data; Decision Making; Detection; Development; Devices; Diagnosis; Diagnostic; Differential Diagnosis; Drops; Early Intervention; Electronics; Environment; Enzyme-Linked Immunosorbent Assay; Event; Film; Fluorescence; Future; Health care facility; Heart Diseases; Heart failure; Hemorrhage; Home; Hospitals; Immunoassay; Manuals; Measurement; Measures; Methods; Modeling; Monitor; Myocardial Infarction; N-terminal; Nanotubes; Nature; Noise; Optics; Outcome; Patient Care; Patient Triage; Patients; Performance; Phase; Play; Polymers; Population; Printing; Proteins; Reader; Reagent; Reproducibility; Research; Risk; Role; Route; Running; Serum; Specimen; System; TNF gene; Technology; Test Result; Testing; Thinness; Training; Transistors; Troponin; United States; Validation; Whole Blood; Work; Writing; acute coronary syndrome; bioelectricity; biomarker validation; blood-based biomarker; cardiac intensive care unit; clinical decision-making; cost; cost effective; data exchange; detection limit; fabrication; implantable device; improved; improved outcome; innovation; innovative technologies; interest; left ventricular assist device; mobile computing; multiplex detection; novel; operation; point of care; point of care testing; portability; predictive marker; preempt; preservation; rapid detection; research clinical testing; scale up; screening; transmission process; user-friendly; virtual

ABSTRACT Heart disease is the leading cause of death in the United States, claiming over 600,000 lives annually. The measurement of blood-based biomarkers to narrow differential diagnoses and triage patients plays a critical role in the management of acute and chronic cardiovascular disease. This R01 project will develop a handheld point- of-care test (POCT) that uses low-cost, disposable assay cassettes to measure multiplexed panels of cardiac biomarkers directly from a drop of whole blood. The assay brings together major advances in carbon nanotubes (CNTs) integrated into thin-film transistors (CNT-TFTs) and an assay platform (called “D4”) for detecting protein analytes with ELISA-like performance from a single drop of blood. Both the CNT-TFTs and D4 are fabricated by printing, making them readily customizable and low cost. CNT-TFTs offer extremely sensitive nanotubes for electrical transduction in an assay and, unlike prior CNT-based biosensors, the CNT-TFTs provide reproducible performance and high yield. The D4 is a fluorescence-based assay that uses antibody (Ab) pairs printed into a polymer brush coating (“POEGMA”) that eliminates background noise and permits highly sensitive measurements directly in complex biological milieu. Merging these two innovative technologies leads to the “D4- TFT”, which combines the electronic sensitivity of the CNT-TFTs with the nonfouling selectivity of the D4 to yield an assay that can rapidly detect biomarker concentration from whole blood without rinsing, via electrical transduction. Extensive preliminary data demonstrate the D4-TFT’s fully printed fabrication, preservation of transistor operation, and successful detection of target analytes from serum and blood. The specific aims of this project include the development of a handheld POCT unit, with all needed control electronics and a simple user interface with display, and adaptation of the D4-TFT to compatible cassettes that are inserted into the handheld unit for operation. Analytical performance of the D4-TFT assay will be maximized and multiplexed against two panels of cardiac biomarkers: (1) A panel of validated cardiac biomarkers that includes creatine kinase (CK), CKMB, troponin (Tn), and N-terminal pro b-type natriuretic peptide (BNP), which are central to the diagnosis and management of a wide spectrum of cardiovascular conditions, including acute chest pain, myocardial infarction, and heart failure (HF); and (2) two investigative cardiac biomarkers, angiopoietin 2 (ANG2) and tumor necrosis factor alpha (TNFα), which are of major interest for their potential association with bleeding events in advanced HF patients with left ventricular assist device (LVAD) implants (the most common complication in this population). These two diverse panels of cardiac biomarkers will demonstrate the versatility and value of this POCT, both for diagnostic potential using validated biomarkers as well as for rapid clinical screening of investigative biomarkers. Accomplishing these aims will lead to a novel POCT for cardiac biomarkers that can be scaled up easily. Its fully printed nature makes the D4-TFT highly customizable and broadly applicable to other blood-based tests for any biomarker with immunoassay reagents.

抽象的 心脏病是美国死亡的主要原因，每年有超过60万人的生命。 测量基于血液的生物标志物来狭窄的鉴别诊断和分类患者起着至关重要的作用 在急性和心血管疾病的管理中 使用低成本的一次性测定盒来测量心脏多工具的护理测试（POCT） 直接从一滴血液中的生物标记物汇总了碳纳米管的主要进步 （CNT）集成到薄膜晶体管（CNT-TFTS）和一个用于驱动蛋白质的测定平台（称为“ D4”） 一滴血液中具有ELISA样性能的分析物。 打印，使它们可以自定义和低成本。 在测定中发电，与先前的基于CNT的生物传感器不同，CNT-TFT可再现 性能和高产量。D4是一种基于荧光的测定 聚合物刷涂层（“ Poegma”）消除了背景噪声并允许高度敏感 直接在复杂的生物环境中进行测量。 TFT”，将CNT-TFT的电子灵敏度与非结合选择性相结合 可以通过电冲洗的全血的生物标志物浓度快速检测到生物标志物浓度 转导数据。 从血清和血液中成功检测目标分析物的特定目的。 项目包括开发手持式POCT单元，并具有所有需要的控制电子设备和简单的用户 展示的接口，并适应D4-TFT到兼容的盒式磁带的接口 D4-TFT分析的分析性能将最大化 心脏生物标志物的面板：（1）一组经过验证的心脏生物标志物，包括肌酸激酶（CK）， CKMB，肌钙蛋白（TN）和N末端B型Natriateratic肽（BNP），这对于诊断和 管理多种心血管疾病的管理，包括急性胸痛，心肌梗塞， 和心力衰竭（HF）和（2）两个调查性心脏生物标志物，Angiopoietin 2（Ang2）和肿瘤坏死 因子alpha（TNFα），这对于该因子具有主要利益。 HF患有左心室辅助装置（LVAD）植入物的患者（Theis人群中最常见的并发症）。 两种不同的心脏生物标志物将证明此POCT的多功能性，均为 使用经过验证的生物标志物以及快速清洁筛网筛查生物标志物的诊断潜力。 实现目标将为心脏生物标志物带来新颖的POTT，可轻松扩展。 印刷性质使D4-TFT高度可定制，并且广泛适用于其他血液测试 具有免疫测定试剂的生物标志物。

项目成果

In-Place Printing of Flexible Electrolyte-Gated Carbon Nanotube Transistors with Enhanced Stability.

• DOI: 10.1109/led.2021.3055787
• 发表时间: 2021-03
• 期刊: IEEE electron device letters : a publication of the IEEE Electron Devices Society
• 作者: Cardenas JA;Lu S;Williams NX;Doherty JL;Franklin AD
• 通讯作者: Franklin AD

Aerosol Jet Printing of SU-8 as a Passivation Layer Against Ionic Solutions.

• DOI: 10.1007/s11664-021-09396-4
• 发表时间: 2022-04
• 期刊: JOURNAL OF ELECTRONIC MATERIALS
• 影响因子: 2.1
• 作者: Ye, Shulin;Williams, Nicholas X.;Franklin, Aaron D.
• 通讯作者: Franklin, Aaron D.

Band gap opening of metallic single-walled carbon nanotubes via noncovalent symmetry breaking.

• DOI: 10.1073/pnas.2317078121
• 发表时间: 2024-03
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Francesco Mastrocinque;George Bullard;James A Alatis;Joseph A Albro;Animesh Nayak;Nicholas X Williams;Amar Kumbhar;Hope Meikle;Zachary X W Widel;Yusong Bai;Alexis K Harvey;Joanna M Atkin;D. Waldeck;Aaron D Franklin;M. Therien

Aerosol Jet Printing Conductive 3D Microstructures from Graphene Without Post-Processing.

• DOI: 10.1002/smll.202305170
• 发表时间: 2023-11
• 期刊: Small
• 影响因子: 13.3
• 作者: Brittany N Smith;P. Ballentine;James L. Doherty;Ryan Wence;Hansel Alex Hobbie;Nicholas X. Williams;Aaron D Franklin

Uniform and Stable Aerosol Jet Printing of Carbon Nanotube Thin-Film Transistors by Ink Temperature Control.

• DOI: 10.1021/acsami.0c12046
• 发表时间: 2020-09-23
• 期刊: ACS applied materials & interfaces
• 影响因子: 9.5
• 作者: Lu S;Zheng J;Cardenas JA;Williams NX;Lin YC;Franklin AD
• 通讯作者: Franklin AD