Nano Monitors for Identification of Vulnerable Cardio-vascular Plaque

2006 ◽  
Vol 926 ◽  
Author(s):  
Shalini Prasad ◽  
Thomas Barrett ◽  
John Carruthers
Keyword(s):  
Complex Disease ◽  
Plaque Rupture ◽  
Coronary Plaque ◽  
Label Free ◽  
Protein Markers ◽  
Protein Biomarkers ◽  
Alumina Membrane ◽  
Non Invasive ◽  
Highly Sensitive ◽  
Cardio Vascular

AbstractWe describe highly sensitive, non–invasive, label-free, electrical detection of protein biomarkers using nanoporous alumina membrane based electrochemical conductance based devices. The principle of operation of these sensors are based on electrochemical conductance varitions associated with the binding of antibody-antigen complexes to a metallic substrate.In these devices distinct pore clusters are selectively surface functionalized with specific antibodies, that are in turn are incorporated into micro scale arrays. Protein markers were routinely detected at nanomolar concentrations. This opens the potential for developing highly sensitive and selective biomarker detection assays in clinically relevant samples for diagnosis of complex disease state like vulnerable coronary plaque rupture that results in poor post surgical outcomes and other complex diseases.

Platform based Detection Technologies from Micro scale to Nanoscale

2006 ◽  
Vol 915 ◽  
Author(s):  
Vindhya Kundura ◽  
Sudhaprasanna Kumar Padigi ◽  
Shalini Prasad
Keyword(s):  
Rapid Identification ◽  
Electrical Signal ◽  
Label Free ◽  
C Reactive Protein ◽  
Protein Biomarkers ◽  
Reactive Protein ◽  
Non Invasive ◽  
Binding Event ◽  
High Throughput Detection ◽  
Detection Technologies

AbstractRapid, multiplexed, high throughput detection of proteins is essential for the development of protein biomarkers as sensors. Electrical alignment and detection is a non-invasive, label free technique for rapid identification of bimolecular. We present here a micro fabricated platform based detector for rapidly identifying protein biomarkers present in atherosclerotic plaque for rapid clinical diagnosis of arterial obstruction. This is achieved by electrical assembly of polystyrene beads functionalized with specific antibody receptors (anti-C-reactive protein) .The electrical assembly is achieved using electrophoresis. The polystyrene “bridge” micro structure formed due to electrical assembly aids in the amplification of the antibody-antigen binding event. Antigen (C-reactive protein) at nanogram / ml concentration was detected when binding of the antigen resulted in an amplification of the electrical signal that was measured from the base microelectrode platform. This technique is a demonstration of the application of microscale technology (electrodes) in nanoscale (protein) electrical detection.

Proteomic profiling of acute coronary thrombosis reveals a local decrease in pigment epithelium-derived factor in acute myocardial infarction

2012 ◽  
Vol 123 (2) ◽  
pp. 111-119 ◽  
Author(s):  
Klaus Distelmaier ◽  
Christopher Adlbrecht ◽  
Johannes Jakowitsch ◽  
Oswald Wagner ◽  
Christopher Gerner ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Plaque Rupture ◽  
Coronary Thrombosis ◽  
Pigment Epithelium ◽  
Coronary Plaque ◽  
Diabetic Patients ◽  
Label Free ◽  
Proteomic Profiling ◽  
Pigment Epithelium Derived Factor

Thrombotic occlusion of an epicardial coronary artery on the grounds of atherosclerotic plaque is considered the ultimate step in AMI (acute myocardial infarction). However, the precise pathophysiological mechanisms underlying acute coronary occlusion are not fully understood. We have analysed proteomic profiles of systemic plasma and plasma derived from the site of coronary plaque rupture of non-diabetic patients with STEMI (ST-segment elevation myocardial infarction). Label-free quantification of MS/MS (tandem MS) data revealed differential regulation of complement cascade components and a decrease in anti-thrombotic PEDF (pigment epithelium-derived factor) between CS (culprit site)-derived plasma and systemic plasma. PEDF, which is known to have a protective role in atherothrombosis, was relatively decreased at the CS, with a level of expression inverse to local MMP-9 (matrix metalloproteinase-9) activity. CS plasma displayed enhanced proteolytic activity towards PEDF. Proteomics of coronary thrombus aspirates indicate that PEDF processing is associated with coronary plaque rupture.

scholarly journals THU0530 HIGHLY-SENSITIVE CARDIAC TROPONIN I AND BETA-2-GLYCOPROTEIN-I IGA ANTIBODIES INFORM THE UTILITY OF SCREENING AND FOLLOW-UP NON-INVASIVE CORONARY ATHEROSCLEROSIS EVALUATION AND OPTIMIZE CARDIOVASCULAR RISK ASSESSMENT IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 504.2-505
Author(s):  
G. Karpouzas ◽  
S. Ormseth ◽  
E. Hernandez ◽  
M. Budoff
Keyword(s):  
Diagnostic Accuracy ◽  
Cardiac Troponin ◽  
Coronary Atherosclerosis ◽  
Troponin I ◽  
Coronary Plaque ◽  
Non Invasive ◽  
Obstructive Disease ◽  
Highly Sensitive ◽  
Iga Antibodies

Background:Occult coronary atherosclerosis burden predicts mid-term cardiovascular disease (CVD) events in rheumatoid arthritis (RA) above and beyond Framingham D’Agostino cardiac risk score (FRS-DA). Highly-sensitive cardiac troponin I (hs-cTnI) levels in blood associate with coronary plaque burden and event risk in RA. Moreover, IgA antibodies against beta2-glycoprotein-1 (a-b2GPI-IgA)- an atherosclerotic plaque antigen- in RA promote coronary plaque progression and moderate the effect of inflammation on CVD events. It is currently unclear when to recommend a screening, non-invasive coronary atherosclerosis evaluation in asymptomatic RA patients and whether such an assessment should be repeated.Objectives:To explore whether either biomarker alone or their combination improved prediction of plaque presence on an initial coronary CT angiogram (CCTA) beyond FRS-DA score; to evaluate whether either biomarker predicted progression to extensive or obstructive plaque on a follow-up evaluation.Methods:One hundred fifty RA patients underwent a baseline CCTA; 101 had repeat evaluation within 6.9±0.3 years. Hs-cTnI and a-b2GPI-IgA were assessed at baseline; the latter were confirmed 12 weeks later, if positive. Lesions rendering greater than 50% luminal stenosis were considered obstructive. Extensive plaque was defined as >5 coronary segments with plaque, or stenosis score>5, or coronary artery calcium score (CAC)>100. The diagnostic accuracy of FRS-DA alone vs. with hs-cTnI or a-b2GPI-IgA individually or combined for plaque or CAC at baseline was evaluated as area under the curve (AUC). Improvement in prediction accuracy between constructs was further assessed as integrated discrimination improvement (IDI). Similar AUC and IDI constructs evaluated the transition to obstructive or extensive atherosclerosis at follow-up in patients with baseline non-extensive or non-obstructive disease.Results:High hs-cTnI (>1.5pg/ml) added to FRS-DA increased AUC from 0.717 to 0.731 (Figure 1A) and improved prediction accuracy for baseline plaque [IDI=0.041 (SE)=0.017, p=0.015]. In contrast, a-b2GPI-IgA did not [IDI=0.005 (0.006), p=0.47] and the combination offered no added benefit to the hs-cTnI model alone. Similar observations were made for CAC. Presence of a-b2GPI-IgA independently associated with coronary plaque progression (IRR=1.67 [95%CI 1.04-2.67]), whereas hs-cTnI did not. Likewise, a-b2GPI-IgA associated with transition to extensive or obstructive disease independently of FRS-DA (OR=13.48 [95%CI 2.09-86.99]). Notably, 71.4% of a-b2GPI-IgA positive patients with high hs-cTnI progressed to extensive or obstructive disease compared to 7.7% of a-b2GPI-IgA negative subjects with high hs-cTnI (p=0.008). Addition of a-b2GPI-IgA to FRS-DA in patients with prevalent non-extensive non-obstructive plaque increased AUC from 0.785 to 0.900 (Figure 1B) and significantly improved the prediction for development of obstructive or extensive atherosclerosis at follow-up [0.387, (0.13), p=0.003].Figure 1.(A) Diagnostic accuracy for prediction of occult coronary atherosclerosis at baseline. FRS-DA alone is the base model followed by addition of hs-cTnI or a-b2GPI-IgA individually or combined.(B) Diagnostic accuracy for progression from non-obstructive and non-extensive plaque at baseline to obstructive or extensive atherosclerosis at follow-up.Conclusion:High hs-cTnI improved the risk of baseline plaque presence beyond clinical risk score and may trigger an initial non-invasive coronary atherosclerosis evaluation. A-b2GPI-IgA presence may justify a follow-up evaluation in patients with non-extensive, non-obstructive plaque at baseline.Disclosure of Interests:George Karpouzas Grant/research support from: Pfizer, Consultant of: Sanofi-Genzyme-Regeneron, Janssen, Speakers bureau: Sanofi-Genzyme-Regeneron, BMS, Sarah Ormseth: None declared, Elizabeth Hernandez: None declared, Matthew Budoff: None declared

scholarly journals Does the Urinary Proteome Reflect ccRCC Stage and Grade Progression?

Diagnostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2369
Author(s):  
Lucia Santorelli ◽  
Martina Stella ◽  
Clizia Chinello ◽  
Giulia Capitoli ◽  
Isabella Piga ◽  
...  
Keyword(s):  
Disease Diagnosis ◽  
Surgical Removal ◽  
Label Free ◽  
Protein Markers ◽  
Cell Renal Cell Carcinoma ◽  
Non Invasive ◽  
Urinary Proteome ◽  
Grading Systems ◽  
Stratified Group ◽  
Molecular Indicators

Due its ability to provide a global snapshot of kidney physiology, urine has emerged as a highly promising, non-invasive source in the search for new molecular indicators of disease diagnosis, prognosis, and surveillance. In particular, proteomics represents an ideal strategy for the identification of urinary protein markers; thus, a urinomic approach could also represent a powerful tool in the investigation of the most common kidney cancer, which is clear cell Renal Cell Carcinoma (ccRCC). Currently, these tumors are classified after surgical removal using the TNM and nuclear grading systems and prognosis is usually predicted based upon staging. However, the aggressiveness and clinical outcomes of ccRCC remain heterogeneous within each stratified group, highlighting the need for novel molecular indicators that can predict the progression of these tumors. In our study, we explored the association between the urinary proteome and the ccRCC staging and grading classification. The urine proteome of 44 ccRCC patients with lesions of varying severity was analyzed via label-free proteomics. MS data revealed several proteins with altered abundance according to clinicopathological stratification. Specifically, we determined a panel of dysregulated proteins strictly related to stage and grade, suggesting the potential utility of MS-based urinomics as a complementary tool in the staging process of ccRCC.

Nano Monitors for Identification of Vulnerable Cardio-Vascular Plaque

2006 ◽  
Vol 915 ◽  
Author(s):  
Ravikiran Kondama Reddy ◽  
Shalini Prasad
Keyword(s):  
Plaque Rupture ◽  
Postoperative Outcome ◽  
Coronary Plaque ◽  
Turnaround Time ◽  
Enzyme Linked Immunosorbent Assay ◽  
Multiple Markers ◽  
Single Marker ◽  
Electrical Biosensors ◽  
Cardio Vascular ◽  
Sensitivity Specificity

AbstractAs our nation's population ages, there will be a substantial demand for surgical services. The best predictor of postoperative outcome is the presence of perioperative ischemia, which is caused by vulnerable coronary plaque rupture. It is not know what makes plaques rupture, but inflammation has been proposed as a unifying etiology. The physiologic perioperative state is one of intense, acute inflammation and thrombosis. This is characterised by the presence of protien- Human Serum C-Reactive Protein( hsCRP) and Myeloperoxidase(MPO). There is a gap in detection capability between gold standard in proteomics detection –Enzyme Linked Immunosorbent Assay (ELISA) assay methods and electrical biosensors.ELISA based protein biomarker detection in too slow to be applicable in early patient bedside treatment. Electrical biosensors on the other hand may overcome this limitation with their improved sensitivity, specificity and rapid detection. In this application we demonstrate the development of nanomembrane based electrical protein “nano monitor”. This technique overcomes the limitations current “state-of- the- art” methods such as:• Specificity in detection of multiple markers that characterizes the disease pathogenesis from a single marker to multiple markers.• Speed of detection from a turnaround time of 12/24 hours to a few minutes.• Sensitivity of detection from milligram/ml to nanogram/ml.

Nanomonitors: Nanomaterial Based Devices Towards Clinical Immunoassays

2008 ◽  
Vol 1095 ◽  
Author(s):  
Shalini Prasad ◽  
Manish Bothara ◽  
Ravikiran Reddy ◽  
John Carruthers ◽  
Thomas Barrett
Keyword(s):  
Specific Protein ◽  
Solid Substrate ◽  
Optical Methods ◽  
Signal Acquisition ◽  
Label Free ◽  
Electrical Detection ◽  
Protein Biomarkers ◽  
Accurate Identification ◽  
Non Invasive ◽  
Diagnostic Applications

AbstractThe immobilization of biomolecules on a solid substrate and their localization in “small” regions are major requirements for a variety of biomedical diagnostic applications, where rapid and accurate identification of multiple biomolecules is essential. In this specific application we have fabricated nanomitors for identifying specific protein biomarkers based on the electrical detection of antibody-antigen binding events.The nanomonitor, lab-on-a-chip device technology is based on electrical detection of protein biomarkers. It is based on developing high density, low volume multi-well plate devices. The scientific core of this technology lies in integrating nanomaterial with micro fabricated chip platforms and exploiting the improve surface area to volume to improve the detection.The devices that have been developed utilize electrical detection mechanisms where capacitance and conductance changes due to protein binding are used as “signatures” for biomarker profiling. In comparison to optical methods, the electrical detection technique is non-invasive as well as a label free. The signal acquisition is simple and it uses the existing data acquisition and signal analysis methods

Label-Free Mass Spectrometry-Based Plasma Proteomics Identified LY6D, DSC3, CDSN, SERPINB12, and SLURP1,as Novel Protein Biomarkers For Pulmonary Tuberculosis

2019 ◽  
Vol 17 ◽  
Author(s):  
Xiaoli Yu ◽  
Lu Zhang ◽  
Na Li ◽  
Peng Hu ◽  
Zhaoqin Zhu ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Search Algorithm ◽  
Differentially Expressed ◽  
P Value ◽  
Plasma Samples ◽  
Label Free ◽  
Protein Biomarkers ◽  
Protein Database ◽  
Leave One Out ◽  
Potential Biomarkers

Aim: We aimed to identify new plasma biomarkers for the diagnosis of Pulmonary tuberculosis. Background: Tuberculosis is an ancient infectious disease that remains one of the major global health problems. Until now, effective, convenient, and affordable methods for diagnosis of Pulmonary tuberculosis were still lacked. Objective: This study focused on construct a label-free LC-MS/MS based comparative proteomics between six tuberculosis patients and six healthy controls to identify differentially expressed proteins (DEPs) in plasma. Method: To reduce the influences of high-abundant proteins, albumin and globulin were removed from plasma samples using affinity gels. Then DEPs from the plasma samples were identified using a label-free Quadrupole-Orbitrap LC-MS/MS system. The results were analyzed by the protein database search algorithm SEQUEST-HT to identify mass spectra to peptides. The predictive abilities of combinations of host markers were investigated by general discriminant analysis (GDA), with leave-one-out cross-validation. Results: A total of 572 proteins were identified and 549 proteins were quantified. The threshold for differentially expressed protein was set as adjusted p-value < 0.05 and fold change ≥1.5 or ≤0.6667, 32 DEPs were found. ClusterVis, TBtools, and STRING were used to find new potential biomarkers of PTB. Six proteins, LY6D, DSC3, CDSN, FABP5, SERPINB12, and SLURP1, which performed well in the LOOCV method validation, were termed as potential biomarkers. The percentage of cross-validated grouped cases correctly classified and original grouped cases correctly classified is greater than or equal to 91.7%. Conclusion: We successfully identified five candidate biomarkers for immunodiagnosis of PTB in plasma, LY6D, DSC3, CDSN, SERPINB12, and SLURP1. Our work supported this group of proteins as potential biomarkers for pulmonary tuberculosis, and be worthy of further validation.

The role of microRNAs in gliomas – Therapeutic implications

2020 ◽  
Vol 13 ◽  
Author(s):  
Theodora Katsila ◽  
Dimitrios Kardamakis
Keyword(s):  
Complex Disease ◽  
Malignant Gliomas ◽  
Kappa Statistic ◽  
Individual Variability ◽  
Response To Treatment ◽  
Disease Phenotype ◽  
Therapeutic Implications ◽  
Non Invasive ◽  
Gene Environment ◽  
Sas Macro

Background: Malignant gliomas constitute a complex disease phenotype that demands optimum decisionmaking. Despite being the most common type of primary brain tumors, gliomas are highly heterogeneous when their pathophysiology and response to treatment are considered. Such inter-individual variability also renders differential and early diagnosis extremely difficult. Recent evidence highlight that the gene-environment interplay becomes of fundamental importance in oncogenesis and progression of gliomas. Objective: To unmask key features of the gliomas disease phenotype and map the inter-individual variability of patients, we explore genotype-to-phenotype associations. Emphasis is put on microRNAs as they regulate gene expression, have been implicated in the pathogenesis of gliomas and may serve as theranostics, empowering non-invasive strategies (circulating free or in exosomes). Method: We mined text and omic datasets (as of 2019) and conducted a mixed-method content analysis. A novel framework was developed to meet the aims of our analysis, interrogating data in terms of content and context. We relied on literature data from PubMed/Medline and Scopus, as they are considered the largest abstract and citation databases of peer-reviewed literature. To avoid selection biases, both publicly available and private texts have been assessed. Both percent agreement and Cohen's kappa statistic have been calculated to avoid biases by SAS macro MAGREE with multicategorical ratings. Results: Gliomas serve as a paradigm for multifaceted datasets, despite data sparsity and scarcity. miRNAs and miRNAbased therapeutics are ready for prime time. Exosomal miRNAs empower non-invasive strategies, surpassing circulating free miRNAs, when accuracy and precision are considered. Conclusion: miRNAs holds promise as theranostics.

scholarly journals Optical Monitoring of the Production Quality of Si-Nanoribbon Chips Intended for the Detection of ASD-Associated Oligonucleotides

Micromachines ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 147
Author(s):  
Kristina A. Malsagova ◽  
Tatyana O. Pleshakova ◽  
Vladimir P. Popov ◽  
Igor N. Kupriyanov ◽  
Rafael A. Galiullin ◽  
...  
Keyword(s):  
Production Quality ◽  
Autism Spectrum ◽  
Covalent Immobilization ◽  
Biological Macromolecules ◽  
Label Free ◽  
Raman Scattering Spectroscopy ◽  
Dna Oligonucleotides ◽  
Highly Sensitive ◽  
Highly Sensitive Detection

Gas-phase etching and optical lithography were employed for the fabrication of a silicon nanoribbon chip (Si-NR chip). The quality of the so-fabricated silicon nanoribbons (Si-NRs) was monitored by optical Raman scattering spectroscopy. It was demonstrated that the structures of the Si-NRs were virtually defect-free, meaning they could be used for highly sensitive detection of biological macromolecules. The Si-NR chips were then used for the highly sensitive nanoelectronics detection of DNA oligonucleotides (oDNAs), which represent synthetic analogs of 106a-5p microRNA (miR-106a-5p), associated with the development of autism spectrum disorders in children. The specificity of the analysis was attained by the sensitization of the Si-NR chip sur-face by covalent immobilization of oDNA probes, whose nucleotide sequence was complementary to the known sequence of miR-106a-5p. The use of the Si-NR chip was demonstrated to al-low for the rapid label-free real-time detection of oDNA at ultra-low (~10−17 M) concentrations.

scholarly journals Role of MRI evaluation in acute secondary inability to walk in children

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
K. H. Sedeek ◽  
K. Aboualfotouh ◽  
S. M. Hassanein ◽  
N. M. Osman ◽  
M. H. Shalaby
Keyword(s):  
Transverse Myelitis ◽  
High Sensitivity ◽  
Acute Disseminated Encephalomyelitis ◽  
Limb Weakness ◽  
Non Invasive ◽  
Highly Sensitive ◽  
Common Causes ◽  
Bilateral Lower Limb ◽  
Severity Of The Disease

Abstract Background Acute bilateral lower limb weakness is a common problem in children which necessitates a rapid method for diagnosis. MRI is a non-invasive imaging technique that produces high-quality images of the internal structure of the brain and spinal cord. Results MRI was very helpful in reaching rapid and prompt diagnosis in children with acute inability to walk. Acute disseminated encephalomyelitis (ADEM), Guillain–Barré syndrome (GBS), and acute transverse myelitis (ATM) were the most common causes in our study. MRI proved to be of high sensitivity in detecting the lesions and reaching the diagnosis in ADEM and GBS; however, there was no significant relation between the lesions’ size, enhancement pattern, and severity of the disease or prognosis, yet in ATM the site of the lesion and number of cord segment affection were significantly related to the severity of the disease and prognosis. Conclusion MRI is a quick tool to reach the diagnosis of children with acute secondary inability to walk, and to eliminate other differential diagnosis which is essential for proper treatment and rapid full recovery. It is highly sensitive in detecting the lesions, their site and size.

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