Protein Biosensor Arrays Based on Nanomaterials

基于纳米材料的蛋白质生物传感器阵列

• 批准号: 8719098
• 负责人: James F. Rusling
• 金额: $ 33.56万
• 依托单位: UNIVERSITY OF CONNECTICUT STORRS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8719098
• 关键词: Antibodies; Biological; Biological Assay; Biological Markers; Biomedical Research; Biosensor; Cancer Control; Cancer Detection; Cancer Patient; Carbon; Cessation of life; Clinical; Clinical Research; Clinical Sensitivity; Collection; Coupled; Decision Making; Detection; Development; Devices; Disease; Drug Targeting; Dyes; Early Diagnosis; Electrodes; Enzymes; Funding; Future; Goals; Immunoassay; Incidence; Label; Letters; Magnetism; Malignant Neoplasms; Malignant neoplasm of prostate; Measurement; Measures; Microfluidics; Modeling; Monitor; National Institute of Dental and Craniofacial Research; Neoplasm Metastasis; Operative Surgical Procedures; Optics; Outcome; Patients; Pharmaceutical Preparations; Predictive Value; Probability; Process; Progress Reports; Prostate-Specific Antigen; Protein Array; Proteins; Proteomics; Protocols documentation; Public Health; Research; Sampling; Screening for cancer; Serum; Speed; Statistical Data Interpretation; System; Systems Biology; Techniques; Testing; Therapeutic; Therapeutic Intervention; Tissues; Translating; United States National Institutes of Health; Viral; Virus; base; cancer cell; cancer diagnosis; cancer surgery; cancer therapy; cost; design; desmoglein III; improved; liquid chromatography mass spectrometry; lymph nodes; malignant mouth neoplasm; nanomaterials; nanoparticle; nanostructured; particle; prototype; response; sensor; surgical research; tool

Measurements of proteins are of central importance in biomedical research, and disease-related applications include early detection, causal identification, and treatment monitoring. Sensitive, specific, fast, inexpensive detection of multiple proteins in patient samples is critically important for future public health. The broad, long term goals of this project are to develop ultrasensitive new array devices for accurate measurements of panels of proteins. Recent research has shown that panels of 4 to 10 biomarker proteins, as opposed to the single biomarkers now used, will provide much more reliable cancer detection and monitoring. We will develop and optimize microfluidic arrays for proteins that are accurate, cheap, and can detect multiple proteins at levels 10-100 fold lower than any commercial alternatives. This project targets arrays for small panels of biomarker proteins in serum and tissue, not proteomic biomarker discovery or analysis. In the past funding period, we developed nanoparticle-based strategies for ultrasensitive protein immunoarrays using many thousands of enzyme labels on magnetic particles for electrochemical detection, or dye-nanoparticle labels for electro-optical detection. We utilized prototype sensors and arrays to detect up to four cancer biomarker proteins in the serum of prostate cancer patients with high accuracy. We recently combined nanostructured sensor arrays with microfluidics and off-line protein capture by the multilabel magnetic-antibody particles. This powerful approach greatly decreases interferences and can detect biomarker proteins in serum at levels of 100 fg mL-1 (~3 fM), 10-100 fold below capabilities of commercial assays. Such high sensitivity provides new opportunities for detection of biomarkers with inherently ultralow levels. This renewal project seeks to translate our ultrasensitive protein detection approaches into the realization of widespread clinical, surgical, and research applications. The deliverables are optimized, validated microfluidic array devices for ultrasensitive detection of virtually any small panel of proteins. A high-speed array for detection of cancer cell metastasis (spreading) to lymph nodes during cancer surgery will also be developed. For proof-of-concept, specific devices will be designed to predict the probability of oral cancer from collections of serum samples, and to clearly distinguish between viral (humanpapilloma virus) and non-viral oral cancers. Patient and control samples obtained by our NIDCR/NIH collaborators will be used to establish clinical sensitivity and selectivity of the immunoassay devices. Summarized specific aims are: (1) Optimize microfluidic systems featuring nanostructured sensor chips and multilabel amperometry for an 8-protein oral cancer panel; (2) Design and optimize a simple electro-optical microfluidic array using dye-nanoparticle labels detected by electrochemiluminescence (ECL); (3) Establish clinical sensitivity and selectivity for oral cancer diagnosis for the best array systems; (4) Develop a rapid microfluidic assay for detection of a metastasis biomarker in lymph nodes. 1

蛋白质的测量在生物医学研究和疾病相关研究中至关重要

项目成果

Low-cost photolithographic fabrication of nanowires and microfilters for advanced bioassay devices.

• DOI: 10.3390/s150306091
• 发表时间: 2015-03-12
• 期刊: Sensors (Basel, Switzerland)
• 作者: Doan NM;Qiang L;Li Z;Vaddiraju S;Bishop GW;Rusling JF;Papadimitrakopoulos F
• 通讯作者: Papadimitrakopoulos F

3D-Printed Fluidic Devices for Nanoparticle Preparation and Flow-Injection Amperometry Using Integrated Prussian Blue Nanoparticle-Modified Electrodes.

• DOI: 10.1021/acs.analchem.5b00903
• 发表时间: 2015
• 期刊: ANALYTICAL CHEMISTRY
• 影响因子: 7.4
• 作者: Bishop, Gregory W.;Satterwhite, Jennifer E.;Bhakta, Snehasis;Kadimisetty, Karteek;Gillette, Kelsey M.;Chen, Eric;Rusling, James F.
• 通讯作者: Rusling, James F.

Multiplexed electrochemical protein detection and translation to personalized cancer diagnostics.

• DOI: 10.1021/ac401058v
• 发表时间: 2013-06-04
• 期刊: ANALYTICAL CHEMISTRY
• 影响因子: 7.4
• 作者: Rusling, James F.

On-line protein capture on magnetic beads for ultrasensitive microfluidic immunoassays of cancer biomarkers.

• DOI: 10.1016/j.bios.2013.09.054
• 发表时间: 2014-03-15
• 期刊: BIOSENSORS & BIOELECTRONICS
• 影响因子: 12.6
• 作者: Otieno, Brunah A.;Krause, Colleen E.;Latus, Alina;Chikkaveeraiah, Bhaskara V.;Faria, Ronaldo C.;Rusling, James F.
• 通讯作者: Rusling, James F.

A biocatalytic cascade with several output signals--towards biosensors with different levels of confidence.

具有多个输出信号的生物催化级联反应 - 带有不同置信度不同的t-towards生物传感器。

• DOI: 10.1007/s00216-014-7789-5
• 发表时间: 2014-05
• 期刊: Analytical and bioanalytical chemistry
• 影响因子: 4.3
• 作者: Guz N;Halámek J;Rusling JF;Katz E
• 通讯作者: Katz E