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.

摘要

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