Highly Sensitive and Fast Detection of C-Reactive Protein and Troponin Biomarkers Using Liquid-gated Single Silicon Nanowire Biosensors

MRS Advances ◽  
2020 ◽  
Vol 5 (16) ◽  
pp. 835-846 ◽  
Author(s):  
Yurii Kutovyi ◽  
Jie Li ◽  
Ihor Zadorozhnyi ◽  
Hanna Hlukhova ◽  
Nazarii Boichuk ◽  
...  

ABSTRACTC-reactive protein (CRP) and cardiac troponin I (cTnI) biomolecules represent the earliest enzymes that appear in the blood when a cardiac injury occurs. Real-time and selective detection of these biomarkers is essential for the prediction and detection of cardiovascular diseases at an early stage. Here we report on the label-free specific detection of both proteins at picomolar concentrations using fabricated nanowire-based biosensors. We demonstrate a novel functionalization technique based on the attachment of dibenzocyclooctyne (DBCO)-linked troponin-specific aptamers to azide-functionalized silicon (Si) nanowire (NW) surface. Due to the fast and reliable immobilization of cTnI-specific aptamers and CRP-specific antibodies on the Si NWs, the fabricated devices can rapidly detect target biomolecules demonstrating high sensitivity. We confirm the attachment of proteins to the surface of Si NWs by atomic force microscopy (AFM). Moreover, we demonstrate that nanowire structures of different sizes enable the detection of biomarkers in a wide concentration range (from 1 pg/ml to 1 µg/ml), corresponding to CRP and cTnI elevation levels during the early stage of disease formation.

Author(s):  
DHEAA SHAMIH ZAGEER ◽  
SUNDUS FADHIL HANTOOSH ◽  
WATHIQ Q SH. ALI

Objectives: This meta-analysis aims to investigate the role of high sensitivity-cardiac troponin I (hs-cTnI) as a prognostic factor for cardiac injury and as a risk factor of death for patients with coronavirus disease 2019 (COVID-19). This meta-analysis studies the impact of hs-cTnI elevated levels on C-reactive protein (C-RP) protein, interleukin-6 (IL-6), and D-dimer (DD) levels in COVID-19 affected individuals. Methods: Of 557 downloaded articles according to chosen criteria for this meta-analysis, 11 were finally chosen as they met the criteria. Results: Male and elderly individuals were noticeably prone to COVID-19 infection and considerably underwent death in comparison with female and young individuals. Levels of hs-cTn I, C-RP, IL-6, and DD were significantly higher among dead compare to survivors for COVID-19 affected individuals. Conclusions: Levels of C-RP, IL-6, and DD were considerably high and in linear relation with elevated hs-cTn I levels. Hs-cTn I can be considered a reliable marker for COVID-19 infection prognosis and potent predictor of decease.


Circulation ◽  
2020 ◽  
Vol 142 (12) ◽  
pp. 1148-1158
Author(s):  
Brendan M. Everett ◽  
M.V. Moorthy ◽  
Jani T. Tikkanen ◽  
Nancy R. Cook ◽  
Christine M. Albert

Background: The majority of sudden cardiac deaths (SCDs) occur in low-risk populations often as the first manifestation of cardiovascular disease (CVD). Biomarkers are screening tools that may identify subclinical cardiovascular disease and those at elevated risk for SCD. We aimed to determine whether the total to high-density lipoprotein cholesterol ratio, high-sensitivity cardiac troponin I, NT-proBNP (N-terminal pro-B-type natriuretic peptide), or high-sensitivity C-reactive protein individually or in combination could identify individuals at higher SCD risk in large, free-living populations with and without cardiovascular disease. Methods: We performed a nested case-control study within 6 prospective cohort studies using 565 SCD cases matched to 1090 controls (1:2) by age, sex, ethnicity, smoking status, and presence of cardiovascular disease. Results: The median study follow-up time until SCD was 11.3 years. When examined as quartiles or continuous variables in conditional logistic regression models, each of the biomarkers was significantly and independently associated with SCD risk after mutually controlling for cardiac risk factors and other biomarkers. The mutually adjusted odds ratios for the top compared with the bottom quartile were 1.90 (95% CI, 1.30–2.76) for total to high-density lipoprotein cholesterol ratio, 2.59 (95% CI, 1.76–3.83) for high-sensitivity cardiac troponin I, 1.65 (95% CI, 1.12–2.44) for NT-proBNP, and 1.65 (95% CI, 1.13–2.41) for high-sensitivity C-reactive protein. A biomarker score that awarded 1 point when the concentration of any of those 4 biomarkers was in the top quartile (score range, 0–4) was strongly associated with SCD, with an adjusted odds ratio of 1.56 (95% CI, 1.37–1.77) per 1-unit increase in the score. Conclusions: Widely available measures of lipids, subclinical myocardial injury, myocardial strain, and vascular inflammation show significant independent associations with SCD risk in apparently low-risk populations. In combination, these measures may have utility to identify individuals at risk for SCD.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yi Jiang ◽  
Subi Abudurexiti ◽  
Meng-Meng An ◽  
Da Cao ◽  
Jie Wei ◽  
...  

AbstractWe aimed to analyse clinical characteristics and identify risk factors predicting all-cause mortality in older patients with severe coronavirus disease 2019 (COVID-19). A total of 281 older patients with severe COVID-19 were categorized into two age groups (60–79 years and ≥ 80 years). Epidemiological, clinical, and laboratory data, and outcome were obtained. Patients aged ≥ 80 years had higher mortality (63.6%) than those aged 60–79 years (33.5%). Anorexia and comorbidities including hypertension, diabetes and COPD, higher levels of lactate dehydrogenase (LDH), osmotic pressure, C-reactive protein, D-dimer, high-sensitivity troponin I and procalcitonin, and higher SOFA scores were more common in patients aged > 80 years than those aged 60–79 years and also more common and higher in non-survivors than survivors. LDH, osmotic pressure, C-reactive protein, D-dimer, high-sensitivity troponin I, and procalcitonin were positively correlated with age and sequential organ failure assessment (SOFA), whereas CD8+ and lymphocyte counts were negatively correlated with age and SOFA. Anorexia, comorbidities including hypertension, diabetes, and chronic obstructive pulmonary disease (COPD), LDH, osmotic pressure, and SOFA were significantly associated with 28-day all-cause mortality. LDH, osmotic pressure and SOFA were valuable for predicting 28-day all-cause mortality, whereas the area under the receiver operating characteristic curve of LDH was the largest, with sensitivity of 86.0% and specificity of 80.8%. Therefore, patients with severe COVID-19 aged ≥ 80 years had worse condition and higher mortality than did those aged 60–79 years, and anorexia and comorbidities including hypertension, diabetes, COPD, elevated plasma osmotic pressure, LDH, and high SOFA were independent risk factors associated with 28-day all-cause mortality in older patients with severe COVID-19. LDH may have the highest predictive value for 28-day all-cause mortality in all examined factors.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Nikorowitsch ◽  
F Ojeda ◽  
K.J Lackner ◽  
R.B Schnabel ◽  
S Blankenberg ◽  
...  

Abstract Background Risk stratification among patients with coronary artery disease (CAD) and acute coronary syndrome (ACS) is of considerable interest due to the potential to guide secondary preventive therapies. Cardiac troponins as well as the inflammatory biomarker C-reactive protein (CRP) and natriuretic peptides have now emerged as useful blood-based biomarkers for risk stratification concerning incident cardiac events. Nevertheless, it has not been tested, whether one of these biomarkers yields predictive value beyond the others. Thus, we evaluated the head-to-head potential of high-sensitivity troponin I (hsTnI), high-sensitivity (hs) CRP and NT-proBNP as prognostic biomarkers for adverse outcome in patients with manifest CAD. Methods Plasma levels of hsTnI, hsCRP and NT-proBNP were measured in a cohort of 2,193 patients with documented CAD –including 837 patients with ACS and 1,356 patients with stable angina pectoris (SAP). Cardiovascular death and/or non-fatal acute myocardial infarction (MI) were defined as the main outcome measures. The association of circulating biomarker levels, used after log-transformation, with cardiovascular mortality and non-fatal MI during follow-up was assessed by Cox proportional hazards analyses adjusted according to three different models including cardiovascular risk factors and either the biomarkers hsCRP, NT-proBNP or hsTnI. Additionally, the net reclassification index (NRI) was calculated using the category five-year event probabilities for two models. Results During a median follow-up of 3.8 years, a total of 231 events were registered (10.5%). All three biomarkers reliably predicted cardiovascular death and/or MI, as evidenced by survival curves stratified for tertiles of circulating levels. In Cox regression analyses with adjustments for sex, age, and conventional cardiovascular risk factors, the hazard ratio (HR) per standard deviation (SD) for the prediction of cardiovascular (CV) death and/or non-fatal MI during follow-up was 1.39 [95% CI: 1.24–1.57, p<0.001] for hsTnI, 1.41 [95% CI: 1.24–1.60, p<0.001] for hsCRP, and 1.64 [95% CI: 1.39–1.92, p<0.001] for NT-proBNP. Nevertheless, upon further adjustment for the other two biomarkers, the significance of the association for hsTnI got lost, association for hsCRP attenuated, and only NT-proBNP kept its predictive value and was still strongly associated with the combined endpoint (1.47 [95% CI: 1.19–1.82, p<0.001]), but also with CV death alone (2.42 [95% CI: 1.86–3.15, p<0.001]). Moreover, only NT-proBNP significantly improved C-statistics and net reclassification index (NRI) for the prediction of cardiovascular death. Conclusions NT-proBNP reliably predicted cardiovascular death and myocardial infarction in patients with manifest CAD and provides incremental value beyond hsCRP and hsTnI. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): “Stiftung Rheinland-Pfalz für Innovation”, Ministry for Science and Education


Author(s):  
Youbin Liu ◽  
Jinglong Li ◽  
Dehui Liu ◽  
Huafeng Song ◽  
Chunlin Chen ◽  
...  

AbstractAimsTo explore the epidemiological and clinical features of 2019 novel coronavirus(2019-nCoV)-infected patients with cardiac injury.Methods and resultsData were collected from patients’ medical records, and we defined cardiac injury according to cardiac biomarker troponin I level > 0.03 μg/L. Among the 291 patients, 15 (5.2%) showed evidence of cardiac injury. Of 15 hospitalized patients with cardiac injury, the median age was 65 years, and 11/15 (73.3%) were men. Underlying cardiovascular diseases in some patients were hypertension (n=7, 46.7%), coronary heart disease (n=3, 20%) and diabetes (n=3, 20%). The most common symptoms at illness onset in patients with cardiac injury were fever (n=11, 73.3%), cough (n=7, 46.7%), headache or fatigue (n=5, 33.3%) and dyspnea (n=4, 26.7%). These patients had higher systolic pressures, white blood cell count, neutrophil count, troponin I, brain natriuretic peptide, D-dimer and lower lymphocyte count, and platelet count, compared with patients without cardiac injury, respectively. Bilateral infiltrates on chest X-ray and elevated C-reactive protein occurred in all patients with cardiac injury. Compared with patients without cardiac injury, patients with cardiac injury were more likely to develop acute respiratory distress syndrome, and receive mechanical ventilation, continuous renal replacement therapy, extracorporeal membrane oxygenation and vasopressor therapy and be admitted to the intensive care unit.ConclusionCardiac injury is a common condition among patients infected with 2019-nCoV. Compared with patients without cardiac injury, the clinical outcomes of patients with cardiac injury are relatively worse.


Sign in / Sign up

Export Citation Format

Share Document