Cardiac biomarkers and the case for point-of-care testing

McDonnell, Barry J.; Hearty, Stephen; Leonard, Paul; O’Kennedy, Richard

doi:10.1016/j.clinbiochem.2009.01.019

Cited by 236 publications

(177 citation statements)

References 162 publications

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“…This leads to an increase of the local refractive index proportional to the analyte concentration. Highly sensitive and label-free detection of molecular species with concentrations down to the ppb-level has been demonstrated in gaseous environments [9]. Specificity can be accomplished by applying multiparameter analysis of different MRR functionalized with, e.g., antibodies exhibiting different binding affinities to a certain target substance.…”

Section: Methodsmentioning

confidence: 99%

Microring resonator arrays for label-free biochemical multiparameter analysis

Pergande¹,

Lützow²,

Gausa³

et al. 2012

Biomedical Engineering / Biomedizinische Technik

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There exist growing demands for robust, reliable, low-cost and easy-to-use sensor systems capable of performing multiparameter analysis for biomedical diagnostics. We have recently demonstrated a particularly economic approach to analyze large arrays of microring resonator (MRR) sensor elements coupled to a single bus waveguide. The sensor elements can be individually functionalized to specifically promote the accumulation of target molecules. The binding of target molecules to the surface of a particular MRR results in a resonance displacement to longer wavelengths, which can be measured with high accuracy. In order to measure the response of the individual MRR from an array to external stimuli, we employ a special frequency modulation scheme in which each MRR is independently modulated and phase sensitive lock-in detection is used to filter the respective frequency component from the superimposed complex transmission spectrum of the bus waveguide. We fabricated test arrays comprising up to 12 MRR coupled to a single bus waveguide. A silicon nitride based material system was chosen to fabricate the devices. Each element of an array is equipped with a platinum heater electrode for thermo-optical modulation. A clear readout of the individual MRR resonance frequencies was possible by employing the modulation scheme above. Furthermore, we demonstrated a bulk refractive index sensitivity of 190 nm/RIU for a frequency modulated MRR. With our first results, we point out the large potential for multiplexed label-free detection of diverse bio molecular compounds. Due to the miniaturization of the multisensor arrays the realization of portable sensor systems will be feasible.

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Section: Methodsmentioning

confidence: 99%

Microring resonator arrays for label-free biochemical multiparameter analysis

Pergande¹,

Lützow²,

Gausa³

et al. 2012

Biomedical Engineering / Biomedizinische Technik

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“…Although there are several alternative commercial techniques and research based biosensors capable of detection limits lower than the demonstrated platform, 15,29 the clinically relevant cut-off levels required for diagnostic use is in the range of 0.01-0.1 ng/ml of biomarker. 15,30,31 Therefore, the detection capabilities of our presented detection platform, with a lower limit of detection (LLD) of 0.08 ng/ml is within the diagnostics threshold and highly applicable for clinical use. In contrast, comparing against a typical clinically implemented point of care device such as the Cobas h232 (Roche Diagnostics LTD), our lower detection limit surpass this benchmark, further reinforcing the point of care (POC) potential of the current platform.…”

Section: A Microlens Validationmentioning

confidence: 99%

Planar lens integrated capillary action microfluidic immunoassay device for the optical detection of troponin I

Mohammed¹,

Desmulliez²

2013

Biomicrofluidics

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Optical based analysis in microfluidic and lab-on-a-chip systems are currently considered the gold standard methodology for the determination of end point reactions for various chemical and biological reaction processes. Typically, assays are performed using bulky ancillary apparatus such as microscopes and complex optical excitation and detection systems. Such instrumentation negates many of the advantages offered by device miniaturisation, particularly with respect to overall portability. In this article, we present a CO 2 laser ablation technique for rapidly prototyping on-chip planar lenses, in conjunction with capillary action based autonomous microfluidics, to create a miniaturised and fully integrated optical biosensing platform. The presented self-aligned on-chip optical components offer an efficient means to direct excitation light within microfluidics and to directly couple light from a LED source. The device has been used in conjunction with a miniaturised and bespoke fluorescence detection platform to create a complete, palm sized system (%60 Â 80 Â 60 mm) capable of performing fluoro-immunoassays. The system has been applied to the detection of cardiac Troponin I, one of the gold standard biomarkers for the diagnosis of acute myocardial infarction, achieving a lower detection limit of 0.08 ng/ml, which is at the threshold of clinically applicable concentrations. The portable nature of the complete system and the biomarker detection capabilities demonstrate the potential of the devised instrumentation for use as a medical diagnostics device at the point of care. V C 2013 AIP Publishing LLC.

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“…Acute events in cardiovascular diseases are here of special concern, and have been successfully diagnosed by monitoring several well-known biomarkers, such as Creatine kinase isoenzyme (CKMB) [5,6], cardiac troponin I or T (Tn) [5,7], brain natriuretic peptide (BNP) [8] and Myoglobin [3,4]. Timely measurements of these biomarkers demands access to low-cost devices, providing rapid responses and capable of operating in point-of-care.…”

Section: Introductionmentioning

confidence: 99%

“…Current techniques used to determine cardiovascular biomarkers rely on immune/antigen reactions, in a wide range of approaches that include counter-immunoelectrophoresis, latex agglutination quantitative microcomplement fixation assay, and radioimmunoassay [4,9,10]. These rely on the great specificity of an antibody towards its antigen, a condition that ensures an easy handling of complex blood samples.…”

Section: Introductionmentioning

confidence: 99%

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Protein-responsive polymers for point-of-care detection of cardiac biomarker

Moreira

Sharma

Dutra

et al. 2014

Sensors and Actuators B: Chemical

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This work describes a novel use for the polymeric film, poly(o-aminophenol) (PAP) that was made respon-sive to a specific protein. This was achieved through templated electropolymerization of aminophenol (AP) in the presence of protein. The procedure involved adsorbing prot ein on the electrode surface and thereafter electroploymerizing the aminophenol. Proteins embedded at the outer surface of the polymeric film were digested by proteinase K and then washed away thereby creating vacant sites. The capacity of the template film to specifically rebind protein was tested with myoglobin (Myo), a cardiac biomarker for ischemia. The films acted as biomimetic artificial antibodies and were produced on a gold (Au) screen printed electrode (SPE), as a step towards disposable sensors to enable point-of-care applications.Raman spectroscopy was used to follow the surface modification of the Au-SPE. The ability of the mate-rial to rebind Myo was measured by electrochemical techniques, namely electrochemical impedance spectroscopy (EIS) and square wave voltammetry (SWV). The d evices displayed linear responses to Myo in EIS and SWV assays down to 4.0 and 3.5 µg/mL, respectively, with detection limits of 1.5 and 0.8 µg/mL. Good selectivity was observed in the presence of troponin T (TnT) and creatine kinase (CKMB) in SWV assays, and accurate results were obtained in applications to spiked serum. The sensor described in this work is a potential tool for screening Myo in point-of-care due to the simplicity of fabrication, disposability, short time response, low cost, good sensitivit y and selectivity.

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Cardiac biomarkers and the case for point-of-care testing

Cited by 236 publications

References 162 publications

Microring resonator arrays for label-free biochemical multiparameter analysis

Microring resonator arrays for label-free biochemical multiparameter analysis

Planar lens integrated capillary action microfluidic immunoassay device for the optical detection of troponin I

Protein-responsive polymers for point-of-care detection of cardiac biomarker

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