Dataset Information

Integrative volumetric bar-chart chip for rapid and quantitative point-of-care detection of myocardial infarction biomarkers.

ABSTRACT: Here we developed an integrated volumetric bar-chart chip (IV-Chip) technology by integration of our previous V-Chip with a fluid handling design to generate an instrument-free POC device and greatly reduce the detection time and effort. The IV-Chip test requires only 1 ?L of serum separated from finger-prick blood. The serum sample and ELISA reagents are directly loaded into the device using a pipette, and a shift of the two layers of the device generates homogeneous liquid segments in the microfluidic channel. Under vacuum pressure generated by a regular syringe, the segments flow into the ELISA wells in sequence and a sandwich ELISA reaction takes place. As a result of the automated washing and reacting strategy, the IV-Chip allows rapid tests for myocardial infarction biomarkers, and turnaround time is greatly reduced to 15 min. The specificity and accuracy of quantitative multiplex detection of MI biomarkers CK-MB, troponin I and myoglobin, are 87.5% and 95.8%, respectively.

SUBMITTER: Song Y

PROVIDER: S-EPMC6434322 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Integrative volumetric bar-chart chip for rapid and quantitative point-of-care detection of myocardial infarction biomarkers.

Song Yujun Y Wang Yuzhen Y Qi Wenjin W Li Ying Y Xuan Jie J Wang Ping P Qin Lidong L

Lab on a chip 20160711 15

Here we developed an integrated volumetric bar-chart chip (IV-Chip) technology by integration of our previous V-Chip with a fluid handling design to generate an instrument-free POC device and greatly reduce the detection time and effort. The IV-Chip test requires only 1 μL of serum separated from finger-prick blood. The serum sample and ELISA reagents are directly loaded into the device using a pipette, and a shift of the two layers of the device generates homogeneous liquid segments in the micr ...[more]

PMID: 27396992

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Project description:BackgroundTraditional preclinical echocardiography (ECHO) modalities, including 1-dimensional motion-mode (M-Mode) and 2-dimensional long axis (2D-US), rely on geometric and temporal assumptions about the heart for volumetric measurements. Surgical animal models, such as the mouse coronary artery ligation (CAL) model of myocardial infarction, result in morphologic changes that do not fit these geometric assumptions. New ECHO technology, including 4-dimensional ultrasound (4D-US), improves on these traditional models. This paper aims to compare commercially available 4D-US to M-mode and 2D-US in a mouse model of CAL.Methods37 mice underwent CAL surgery, of which 32 survived to a 4?week post-operative time point. ECHO was completed at baseline, 1?week, and 4?weeks after CAL. M-mode, 2D-US, and 4D-US were taken at each time point and evaluated by two separate echocardiographers. At 4?weeks, a subset (n =?12) of mice underwent cardiac magnetic resonance (CMR) imaging to serve as a reference standard. End systolic volume (ESV), end diastolic volume (EDV), and ejection fraction (EF) were compared among imaging modalities. Hearts were also collected for histologic evaluation of scar size (n =?16) and compared to ECHO-derived wall motion severity index (WMSI) and global longitudinal strain as well as gadolinium-enhanced CMR to compare scar assessment modalities.Results4D-US provides close agreement of ESV (Bias: -2.55%, LOA: -?61.55 to 66.66) and EF (US Bias: 11.23%, LOA -?43.10 to 102.8) 4?weeks after CAL when compared to CMR, outperforming 2D-US and M-mode estimations. 4D-US has lower inter-user variability as measured by intraclass correlation (ICC) in the evaluation of EDV (0.91) and ESV (0.93) when compared to other modalities. 4D-US also allows for rapid assessment of WMSI, which correlates strongly with infarct size by histology (r?=?0.77).Conclusion4D-US outperforms M-Mode and 2D-US for volumetric analysis 4?weeks after CAL and has higher inter-user reliability. 4D-US allows for rapid calculation of WMSI, which correlates well with histologic scar size.

Project description:BACKGROUND: A significant proportion of myocardial infarction (MI) patients undergo complex, coordinated perturbations at the molecular level that may eventually drive the occurrence of ventricular dysfunction and heart failure. Despite advances in the elucidation of key processes implicated in this condition, traditional methods relying on gene expression data and the identification of individual biomarkers in isolation pose major limitations not only for improving prediction power, but also for model interpretability. Mechanisms underlying clinical responses after MI remain elusive and there is no biomarker with the capacity to accurately predict ventricular dysfunction after MI. This calls for the exploration of system-level modeling of ventricular dysfunction in post-MI patients. Within this discovery framework key perturbations and predictive patterns are characterized by the integrated biological activity levels observed in pathways, rather than in individual genes. METHODOLOGY/PRINCIPAL FINDINGS: Here we report an integrative approach to identifying pathways related with ventricular dysfunction post MI with potential prognostic and therapeutic value. We found that a diversity of pathway-level perturbations can be profiled in samples of patients with ventricular dysfunction post MI, most of which represent major reductions of gene expression. Highly perturbed pathways included those implicated in antigen-dependent B-cell activation and the synthesis of leucine. By analyzing patient-specific samples encoded with information derived from highly-perturbed pathways, it is possible to visualize differential prognostic patterns and to perform computational classification of patients with areas under the receiver operating characteristic curve above 0.75. We also demonstrate how the integration of the outcomes generated by different pathway-based analysis models may improve ventricular dysfunction prediction performance. SIGNIFICANCE: This research offers an alternative, comprehensive view of key relationships and perturbations that may trigger the emergence or prevention of ventricular dysfunction post-MI.

Dataset Information

Integrative volumetric bar-chart chip for rapid and quantitative point-of-care detection of myocardial infarction biomarkers.

Publications

Integrative volumetric bar-chart chip for rapid and quantitative point-of-care detection of myocardial infarction biomarkers.

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