Novel Biomarkers and Advanced Cardiac Imaging in Aortic Stenosis: Old and New.

Currently, the symptomatic status and left ventricular ejection fraction (LVEF) play a crucial role in aortic stenosis (AS) assessment. However, the symptoms are often subjective, and LVEF is not a sensitive marker of left ventricle (LV) decompensation. Over the past years, the cardiac structure and function research on AS has increased due to advanced imaging modalities and potential therapies. New imaging parameters emerged as predictors of disease progression in AS. LV global longitudinal strain has proved useful for risk stratification in asymptomatic severe AS patients with preserved LVEF. The assessment of myocardial fibrosis by cardiac magnetic resonance is the most studied application and offers prognostic information on AS. Moreover, the usage of biomarkers in AS as objective measures of LV decompensation has recently gained more interest. The present review focuses on the transition from compensatory LV hypertrophy (H) to LV dysfunction and the biomarkers associated with myocardial wall stress, fibrosis, and myocyte death. Moreover, we discuss the potential impact of non-invasive imaging parameters for optimizing the timing of aortic valve replacement and provide insight into novel biomarkers for possible prognostic use in AS. However, data from randomized clinical trials are necessary to define their utility in daily practice.

Right ventricle to pulmonary artery coupling after transcatheter aortic valve implantation-Determinant factors and prognostic impact.

Introduction: Right ventricular (RV) dysfunction and pulmonary hypertension (PH) have been previously associated with unfavorable outcomes in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI), but little is known about the effect of right ventricle (RV) to pulmonary artery (PA) coupling. Our study aimed to evaluate the determinant factors and the prognostic value of RV-PA coupling in patients undergoing TAVI. Methods: One hundred sixty consecutive patients with severe AS were prospectively enrolled, between September 2018 and May 2020. They underwent a comprehensive echocardiogram before and 30 days after TAVI, including speckle tracking echocardiography (STE) for myocardial deformation analysis of the left ventricle (LV), left atrium (LA), and RV function. Complete data on myocardial deformation was available in 132 patients (76.6 ± 7.5 years, 52.5% men) who formed the final study population. The ratio of RV free wall longitudinal strain (RV-FWLS) to PA systolic pressure (PASP) was used as an estimate of RV-PA coupling. Patients were analyzed according to baseline RV-FWLS/PASP cut-off point, determined through time-dependent ROC curve analysis, as follows: normal RV-PA coupling group (RV-FWLS/PASP ≥0.63, n = 65) and impaired RV-PA coupling group (RV-FWLS/PASP < 0.63, n = 67). Results: A significant improvement of RV-PA coupling was observed early after TAVI (0.75 ± 0.3 vs. 0.64 ± 0.3 before TAVI, p < 0.001), mainly due to PASP decrease (p < 0.001). LA global longitudinal strain (LA-GLS) is an independent predictor of RV-PA coupling impairment before and after TAVI (OR = 0.837, p < 0.001, OR = 0.848, p < 0.001, respectively), while RV diameter is an independent predictor of persistent RV-PA coupling impairment after TAVI (OR = 1.174, p = 0.002). Impaired RV-PA coupling was associated with a worse survival rate (66.3% vs. 94.9%, p-value < 0.001) and emerged as an independent predictor of mortality (HR = 5.97, CI = 1.44-24.8, p = 0.014) and of the composite endpoint of death and rehospitalization (HR = 4.14, CI = 1.37-12.5, p = 0.012). Conclusion: Our results confirm that relief of aortic valve obstruction has beneficial effects on the baseline RV-PA coupling, and they occur early after TAVI. Despite significant improvement in LV, LA, and RV function after TAVI, RV-PA coupling remains impaired in some patients, it is mainly related to persistent pulmonary hypertension and is associated with adverse outcomes.

Role of advanced left ventricular imaging in adults with aortic stenosis.

This review focuses on the available data regarding the utility of advanced left ventricular (LV) imaging in aortic stenosis (AS) and its potential impact for optimising the timing of aortic valve replacement. Ejection fraction is currently the only LV parameter recommended to guide intervention in AS. The cut-off value of 50%, recommended for decision-making in asymptomatic patients with AS, is currently under debate. Several imaging parameters have emerged as predictors of disease progression and clinical outcomes in this setting. Global longitudinal LV strain by speckle tracking echocardiography is useful for risk stratification of asymptomatic patients with severe AS and preserved LV ejection fraction. Its prognostic value was demonstrated in these patients, but further work is required to define the best thresholds to aid the decision-making process. The assessment of myocardial fibrosis is the most studied application of cardiac magnetic resonance in AS. The detection of replacement fibrosis by late gadolinium enhancement offers incremental prognostic information in these patients. Clinical implementation of this technique to optimise the timing of aortic valve intervention in asymptomatic patients is currently tested in a randomised trial. The use of T1 mapping techniques can provide an assessment of interstitial myocardial fibrosis and represents an expanding field of interest. However, convincing data in patients with AS is still lacking. All these imaging parameters have substantial potential to influence the management decision in patients with AS in the future, but data from randomised clinical trials are awaited to define their utility in daily practice.

Polyolefin-Supported Hydrogels for Selective Cleaning Treatments of Paintings.

Surface decontamination is of general concern in many technical fields including optics, electronics, medical environments, as well as art conservation. In this respect, we developed thin copolymer networks covalently bonded to flexible polyethylene (PE) sheets for hydrogel-based cleaning of varnished paintings. The syntheses of acrylates and methacrylates of the surfactants Triton X-100, Brij 35, and Ecosurf EH-3 or EH-9 and their incorporation into copolymers with acrylamide (PAM) and N-(4-benzoylphenyl)acrylamide are reported. Photocrosslinked polymer networks were prepared from these copolymers on corona-treated PE sheets, which can be swollen with aqueous solution to form hydrogel layers. The cleaning efficacy of these PE-PAM hydrogel systems, when swollen with appropriate cleaning solutions, was evaluated on painting surfaces in dependence of the PAM copolymer composition and degree of crosslinking. Specifically, soil and varnish removal and varnish surface solubilization were assessed on mock-ups as well as on paintings, indicating that even surfactant-free cleaning solutions were effective.

Point-of-care echocardiographic screening for left-sided valve heart disease: high yield and affordable cost in an elderly cohort recruited in primary practice.

BACKGROUND: Data about the epidemiology of valvular heart disease (VHD) in the elderly is scarce. Hand-held ultrasound devices (HUDs) enable point-of-care ultrasound scanning (POCUS) but their use in an elderly population has not been reported for VHD screening in primary practice. METHODS: One hundred consecutive subjects aged >70 years without a VHD diagnosis had 2D and colour Doppler POCUS by an accredited sonographer, using a contemporary HUD (Vscan), in a primary practice setting. Patients with left-sided valve pathology identified by Vscan were referred for formal echo in the local tertiary cardiac centre. RESULTS: Mean age (s.d.) was 79.08 (3.74) years (72-92 years); 61 female. By Vscan, we found five patients with ≥moderate aortic stenosis (AS), eight with ≥moderate mitral regurgitation (MR) and none with ≥moderate aortic regurgitation. In the AS and MR groups each, one patient had valve intervention following from the initial diagnosis by Vscan, two and one respectively are under follow-up in the valve clinic, while two and four respectively refused TTE or follow-up. Two patients with moderate MR by Vscan had mild and mild/moderate MR respectively by TTE and were discharged. Total cost for scanning 100 patients was $18,201 - i.e. $182/patient. CONCLUSIONS: Screening with a hand-held scanner (Vscan), we identified 5/100 elderly subjects who needed valve replacement or follow-up in valve clinic, at a cost of $182/patient. These findings have potential significance for the allocation of resources in the context of an ageing population.

Left Atrial Dysfunction as an Independent Correlate of Heart Failure Symptoms in Patients With Severe Aortic Stenosis and Preserved Left Ventricular Ejection Fraction.

BACKGROUND: Data regarding the contribution of left atrial (LA) dysfunction to the occurrence of heart failure in patients with severe aortic stenosis (AS) are scarce. The aim of this study was to assess the relationship between LA deformation and symptomatic status in this clinical setting. METHODS: A total of 361 consecutive patients with severe AS (aortic valve area [AVA] index ≤ 0.6 cm2/m2) referred to the echocardiography laboratory were prospectively screened. Two hundred forty-eight patients with preserved left ventricular (LV) ejection fraction (≥50%), in sinus rhythm, and with no more than mild aortic or mitral regurgitation (202 symptomatic and 46 asymptomatic) were enrolled. Asymptomatic status was confirmed by exercise echocardiography or electrocardiography, as clinically indicated. All patients underwent comprehensive echocardiography, including speckle-tracking analysis of LV and LA deformation. RESULTS: No significant differences were found between the two groups regarding age and cardiovascular risk factors. LV ejection fraction and geometric parameters were similar between groups despite higher indexed AVA in asymptomatic patients. In symptomatic patients, brain natriuretic peptide values, average E/e' ratio, and LA size were higher, whereas LV global longitudinal strain and peak LA longitudinal strain and strain rate parameters were lower compared with asymptomatic patients. AVA and peak systolic LA longitudinal strain rate were the only independent correlates of heart failure symptoms (P = .04 and P = .01, respectively). CONCLUSIONS: LA systolic strain rate, in addition to AVA, emerged as an independent correlate of the presence of heart failure in patients with severe AS and preserved LV ejection fraction. The echocardiographic evaluation of LA function by speckle-tracking may become useful for risk stratification in patients with asymptomatic AS, but larger prospective studies are needed.

Left atrial dysfunction as a determinant of pulmonary hypertension in patients with severe aortic stenosis and preserved left ventricular ejection fraction.

In patients with severe aortic stenosis (AS), the presence of pulmonary hypertension (PH) has been linked to a poor prognosis. We aimed to assess the main determinants of PH in patients with severe AS and preserved left ventricular ejection fraction (LVEF). We prospectively enrolled 108 consecutive patients with isolated severe AS (indexed aortic valve area <0.6 cm2/m2) and LVEF >50%, in sinus rhythm. Left atrial (LA) function was assessed using longitudinal deformation parameters (by speckle tracking echocardiography). PH (defined as systolic pulmonary artery pressure >40 mmHg) was present in 20 patients. Patients with severe AS and PH were older (p = 0.05), had higher BNP values (p = 0.05) and a greater degree of LV diastolic dysfunction: higher E/e' and E/A ratios and lower EDT values (p < 0.03 for all) compared to patients without PH. There were no differences between groups regarding AS severity and LV systolic function parameters. Patients with PH had a more impaired LA function: lower septal and lateral late diastolic peak velocity a' (p < 0.001 and p = 0.04 respectively) and lower LA peak longitudinal strain and strain rate parameters (p ≤ 0.005 for all). In multivariable analysis, LA late diastolic longitudinal strain rate was the only independent correlate of PH in our patients (p = 0.04). Patients with isolated severe AS, preserved LVEF and PH had larger LA volumes, a more impaired LA function, and higher LV filling pressures compared to those without PH. LA booster pump function, reflected by late diastolic longitudinal strain rate, emerged as an independent correlate of PH in these patients.

Echo-Doppler estimation of left ventricular filling pressure: results of the multicentre EACVI Euro-Filling study.

AIMS: The present Euro-Filling report aimed at comparing the diagnostic accuracy of the 2009 and 2016 echocardiographic grading algorithms for predicting invasively measured left ventricular filling pressure (LVFP). METHOD AND RESULTS: A total of 159 patients who underwent simultaneous evaluation of echo estimates of LVFP and invasive measurements of LV end-diastolic pressure (LVEDP) were enrolled at nine EACVI centres. Thirty-nine (25%) patients had a reduced LV ejection fraction (<50%), 77 (64%) were in NYHA ≥ II, and 85 (53%) had coronary artery disease. Sixty-four (40%) patients had elevated LVEDP (≥15 mmHg). Taken individually, all echocardiographic Doppler estimates of LVFP (E/A, E/e', left atrial volume, tricuspid regurgitation jet velocity) were marginally correlated with LVEDP. By using the 2016 recommendations, 65% of patients with normal non-invasive estimate of LVFP had normal LVEDP, while 79% of those with elevated non-invasive LVFP had elevated invasive LVEDP. By using 2009 recommendations, 68% of the patients with normal non-invasive LVFP had normal LVEDP, while 55% of those with elevated non-invasive LVFP had elevated LVEDP. The 2016 recommendations (sensitivity 75%, specificity 74%, positive predictive value 39%, negative predictive value 93%, AUC 0.78) identified slightly better patients with elevated invasive LVEDP (≥ 15 mmHg) as compared with the 2009 recommendations (sensitivity 43%, specificity 75%, positive predictive value 49%, negative predictive value 71%, AUC 0.68). CONCLUSION: The present Euro-Filling study demonstrates that the new 2016 recommendations for assessing LVFP non-invasively are fairly reliable and clinically useful, as well as superior to the 2009 recommendations in estimating invasive LVEDP.

A Congenital Gerbode Defect associated with a Rare Structural Abnormality of the Mitral Valve Diagnosed in an Adult Patient.

We report the case of a rare association of a congenital Gerbode defect with severe mitral regurgitation due to abnormal linear structure of mitral valve, diagnosed in an adult patient. The case highlights the importance of a thorough examination interpreting the echocardiographic findings on a pathophysiological basis. It also underlines the complementary role of different imaging techniques with transesophageal echocardiography, allowing the precise assessment of both structural and functional abnormalities in such a complex case. The patient underwent mitral valve replacement with a bileaflet mechanical prosthesis and repair of the Gerbode defect. The imaging findings were confirmed during the surgical procedure, leading to a good outcome.

Right ventricular remodeling, its correlates, and its clinical impact in hypertrophic cardiomyopathy.

BACKGROUND: Structural right ventricular (RV) abnormalities are present in a substantial proportion of patients with hypertrophic cardiomyopathy (HCM), but the trigger for RV hypertrophy remains unclear. The aim of this study was to assess the relationship between RV and left ventricular (LV) remodeling and the impact of biventricular involvement on clinical status in this setting. METHODS: Ninety-nine patients with HCM and 30 normal subjects with a similar age and gender distribution were prospectively enrolled. Comprehensive echocardiography was performed in all, including the assessment of LV and RV function by tissue Doppler and speckle-tracking echocardiography. Measurement of RV free wall thickness (RVWT) was performed at end-diastole, in a zoomed subcostal view, focusing on the RV midwall. RESULTS: Patients with HCM had increased RVWT (6.4 ± 1.9 vs 3.6 ± 0.8 mm, P < .001) and lower values of RV global longitudinal strain (-19.4 ± 4.4% vs -23.8 ± 2.7%, P < .001) compared with control subjects. RVWT was independently related to LV mass and LV global longitudinal strain. Increased RVWT was correlated with New York Heart Association class (r = 0.20, P = .04) and calculated sudden cardiac death risk score (r = 0.52, P < .001) and was independently related to the presence of ventricular arrhythmias (odds ratio, 2.02; 95% CI, 1.28-3.19; P = .002). CONCLUSIONS: In patients with HCM, the presence of RV hypertrophy was associated with increased LV mass and reduced LV longitudinal strain, correlated with increased calculated sudden cardiac death risk score, and independently related to the presence of ventricular arrhythmias. These data suggest more severe disease in patients with biventricular HCM.

The left ventricle in aortic stenosis--imaging assessment and clinical implications.

Aortic stenosis has an increasing prevalence in the context of aging population. In these patients non-invasive imaging allows not only the grading of valve stenosis severity, but also the assessment of left ventricular function. These two goals play a key role in clinical decision-making. Although left ventricular ejection fraction is currently the only left ventricular function parameter that guides intervention, current imaging techniques are able to detect early changes in LV structure and function even in asymptomatic patients with significant aortic stenosis and preserved ejection fraction. Moreover, new imaging parameters emerged as predictors of disease progression in patients with aortic stenosis. Although proper standardization and confirmatory data from large prospective studies are needed, these novel parameters have the potential of becoming useful tools in guiding intervention in asymptomatic patients with aortic stenosis and stratify risk in symptomatic patients undergoing aortic valve replacement.This review focuses on the mechanisms of transition from compensatory left ventricular hypertrophy to left ventricular dysfunction and heart failure in aortic stenosis and the role of non-invasive imaging assessment of the left ventricular geometry and function in these patients.

Temperature-Tunable Nanoparticles for Selective Biointerface.

Drugs can be delivered by a temperature change-driven shrinking of the nanocarrier followed by the cargo release. This paper describes a different structural response to temperature, performed by nanoparticles of poly(N-isopropylacrylamide) and hyaluronic acid. Around 35 °C, the hydrophobicity of the vinyl polymer drives a core-shell rearrangement with the acrylamide chains confined in the core and the polysaccharide moiety forming the shell. In this arrangement, the nanoparticles enable the active targeting of tumor cells, due to the specific interaction of hyaluronic acid with the CD44 receptors. When doxorubicin-loaded nanoparticles are up-taken, the polysaccharide part degrades in the cytoplasm and the cytotoxic effect of the anticancer drug in colon adenocarcinoma cells has a 2-fold increase with respect to healthy fibroblasts. These core-shell particles have hyaluronic acid as the key factor for the specific targeting of tumor cells and drug release with poly(N-isopropylacrylamide) driving the transition.

Impact of metabolic syndrome traits on cardiovascular function: should the Adult Treatment Panel III definition be further stratified?

AIMS: The aims of the study were to evaluate whether a further classification of metabolic syndrome according to the number of traits (based on the Adult Treatment Panel III definition) could better explain the impact on cardiovascular remodeling and function, and to assess the role of single metabolic syndrome components in this regard. METHODS: We studied by echocardiography and carotid ultrasound 435 asymptomatic patients with metabolic syndrome. Patients with coronary artery disease or more than mild valvular heart disease were excluded. Carotid stiffness index (ß) was measured using a high-resolution echo-tracking system. Patients with metabolic syndrome were divided into two groups: metabolic syndrome with three traits (Gr.1) and metabolic syndrome with four or five traits (Gr. 2). RESULTS: Patients in Gr. 2 had higher left ventricular mass index (P < 0.001), left ventricular end-diastolic volume index (P = 0.029), left atrial volume index (P = 0.002), E/e' ratio (P = 0.002), intima-media thickness (P = 0.031), and prevalence of plaques (P = 0.01) than patients in Gr. 1. Left ventricular ejection fraction was similar in both groups. The mean carotid ß index tended to be higher in Gr. 2. Considering metabolic syndrome traits separately, in an age-corrected multivariate analysis, abdominal obesity was found to have the strongest association with cardiac structure and carotid artery atherosclerosis and stiffness. CONCLUSION: An increasing number of metabolic syndrome traits had a significantly worse impact on cardiac remodeling and function and carotid artery atherosclerosis. Abdominal obesity showed the strongest association with cardiac structure, carotid artery stiffness, and intima-media thickness. Prospective studies are needed to evaluate whether a new classification of metabolic syndrome using the number of traits could add prognostic information.

Cardiac structure and function and insulin resistance in morbidly obese patients: does superobesity play an additional role?

OBJECTIVE: To evaluate the impact of superobesity, defined as body mass index (BMI) ≥50, on cardiac structure and function. METHODS: Using echocardiography, we studied 198 asymptomatic patients (mean age 48 ± 13 years, 29.3% were men) with a BMI ≥40. Insulin resistance was measured using the Homeostasis Model Assessment of insulin resistance (HOMA-IR). Patients were divided into 2 groups: morbidly obese (BMI ≥40 and <50; n = 160) and superobese (BMI ≥50; n = 38). RESULTS: There were no significant differences in age, gender, hypertension and diabetes between groups. Superobese patients had higher LV mass (66.0 ± 14.7 vs. 59.9 ± 11.9 g/m(2.7), p = 0.007), left ventricular (LV) end-diastolic (33.8 ± 7.7 vs. 31.5 ± 7.1 ml/m(2.7), p = 0.041) and end-systolic (12.2 ± 3.6 vs. 10.9 ± 2.8 ml/m(2.7), p = 0.016) volumes, left atrial volume (13.8 ± 4.5 vs. 12.2 ± 3.9 ml/m(2.7), p = 0.029), peak velocity of transmitral flow in early diastole/early diastolic peak myocardial velocity ratio (9.1 ± 2.6 vs. 8.2 ± 2.2, p = 0.03) and HOMA-IR (9.7 ± 7.3 vs. 7.3 ± 6.5, p = 0.047). LV ejection fraction was similar. CONCLUSIONS: Superobesity is associated with insulin resistance and a worse impact on cardiac remodeling and LV diastolic function than morbid obesity. Prospective studies are needed to evaluate whether such further classification of morbid obesity could stratify the cardiovascular risk in these patients more accurately.

The role of statin treatment in valvular heart disease: is the jury still out?

Valvular heart disease (VHD) represents a significant burden within the spectrum of cardiovascular diseases. In recent years, there has been a great interest in finding medical treatments able to slow the progression ofVHD. The negative results of several large randomized trials failing to demonstrate a benefit of such therapies, has led to a decrease of interest in this field. However, finding a medical treatment capable of preventing VHD progression is still a hot topic, due to the important clinical implications. We believe that the jury is still out on the debate about the role of statin therapy in VHD, considering also recently published studies providing new information with future implications for the treatment of this disease process. This article gives an overview of the published evidence about the role of hydroxymethylglutaryl coenzyme-A reductase inhibitors on delaying progressive valve dysfunction. A preventive therapy, which could influence not only the haemodynamic progression of valve disease, but also the cardiovascular outcome, is warranted. Large, prospective, randomized trials are needed to properly evaluate the role of statins in the early stages of valvular heart disease.

Active Control of SPR by Thermoresponsive Hydrogels for Biosensor Applications.

The use of thermoresponsive poly(N-isopropylacrylamide)-based hydrogel (pNIPAAm) for rapid tuning of surface plasmon resonance (SPR) is reported. This approach is implemented by using an SPR layer architecture with an embedded indium tin oxide microheater and pNIPAAm film on its top. It takes advantage of rapid thermally induced swelling and collapse of pNIPAAm that is accompanied by large refractive index changes and leads to high thermo-optical coefficient of dn/dT = 2 × 10-2 RIU/K. We show that this material is excellently suited for efficient control of refractive index-sensitive SPR and that it can serve simultaneously as a 3D binding matrix in biosensor applications (if modified with biomolecular recognition elements for a specific capture of target analyte). We demonstrate that this approach enables modulating of the output signal in surface plasmon-enhanced fluorescence spectroscopy biosensors and holds potential for simple time-multiplexing of sensing channels for parallelized readout of fluorescence assays.

Biosensor based on hydrogel optical waveguide spectroscopy for the detection of 17ß-estradiol.

Rapid detection of hormones at sub-ng/ml concentrations is of tremendous importance for diagnostic purposes, quality control, and environmental monitoring. In this respect, we report a novel label-free biosensor based on hydrogel optical waveguide spectroscopy (HOWS) for the sensitive detection of 17ß-estradiol (E2). This approach was implemented by using a thin hydrogel layer of a carboxylated poly(N-isoproprylacrylamide) (PNIPAAm) terpolymer that was attached to a metallic sensor surface in order to simultaneously serve as a binding matrix and an optical waveguide. Refractive index changes that are accompanied with the specific capture of biomolecules from an aqueous sample on the sensor surface were probed by resonantly excited hydrogel optical waveguide modes. To optically excite and interrogate these waves, an optical setup based on Kretschmann configuration of attenuated total reflection (ATR) method that is compatible with surface plasmon resonance (SPR) was used. We demonstrate that HOWS offers a higher binding capacity, good anti-fouling properties, improved figure of merit, and E2 detection limit of 50 pg/ml which is seven times better than that obtained by a regular surface plasmon resonance (SPR) biosensor.

Bloch surface wave-enhanced fluorescence biosensor.

A new approach to signal amplification in fluorescence-based assays for sensitive detection of molecular analytes is reported. It relies on a sensor chip carrying a one-dimensional photonic crystal (1DPC) composed of two piled up segments which are designed to increase simultaneously the excitation rate and the collection efficiency of fluorescence light. The top segment supports Bloch surface waves (BSWs) at the excitation wavelength and the bottom segment serves as a Bragg mirror for the emission wavelength of used fluorophore labels. The enhancement of the excitation rate on the sensor surface is achieved through the resonant coupling to BSWs that is associated with strong increase of the field intensity. The increasing of collection efficiency of fluorescence light emitted from the sensor surface is pursued by using the Bragg mirror that minimizes its leakage into a substrate and provides its beaming toward a detector. In order to exploit the whole evanescent field of BSW, extended three-dimensional hydrogel-based binding matrix that is functionalized with catcher molecules is attached to 1DPC for capturing of target analyte from a sample. Simulations supported by experiments are presented to illustrate the design and determined the performance characteristics of BSW-enhanced fluorescence spectroscopy. A model immunoassay experiment demonstrates that the reported approach enables increasing signal to noise ratio, resulting in about one order of magnitude improved limit of detection (LOD) with respect to regular total internal reflection fluorescence (TIRF) configuration.

Simultaneous measurement of mechanical and surface properties in thermoresponsive, anchored hydrogel films.

Hydrogel films have been used extensively in the preparation of biosensors and biomedical devices. The characteristics of the aqueous interface of the polymer layer are significant for the biosensor or device function; likewise, the changing mechanical properties of thermoresponsive polymers are an important feature that affects the polymer behavior. Atomic force microscopy was used here to characterize both the surface and the mechanical properties of polymeric hydrogel films prepared from a thermoresponsive terpolymer of N-isopropylacrylamide and acrylic acid with benzophenonemethacrylate as a photoreactive cross-linker comonomer. The force-distance curves thus obtained were analyzed to assess both the surface forces and the mechanical response that were associated with the hydrogel. These properties were investigated as a function of temperature, in water and in Tris buffer, for different degrees of polymer cross-linking. For samples in water, the distance over which the surface forces were effective was found to remain constant as the temperature was increased from 26 to 42 °C, even though the mechanical response indicated that the samples had been heated past the lower critical solution temperature, or LCST. The bulk of the polymer becomes less soluble above the LCST, although this does not seem to affect the surface properties. This may be due to the segregation of the acrylic acid-rich polymer segments near the gel surface, which is in agreement with reports for related systems.

Thin hydrogel films for optical biosensor applications.

Hydrogel materials consisting of water-swollen polymer networks exhibit a large number of specific properties highly attractive for a variety of optical biosensor applications. This properties profile embraces the aqueous swelling medium as the basis of biocompatibility, non-fouling behavior, and being not cell toxic, while providing high optical quality and transparency. The present review focuses on some of the most interesting aspects of surface-attached hydrogel films as active binding matrices in optical biosensors based on surface plasmon resonance and optical waveguide mode spectroscopy. In particular, the chemical nature, specific properties, and applications of such hydrogel surface architectures for highly sensitive affinity biosensors based on evanescent wave optics are discussed. The specific class of responsive hydrogel systems, which can change their physical state in response to externally applied stimuli, have found large interest as sophisticated materials that provide a complex behavior to hydrogel-based sensing devices.