Towards monitoring real-time cellular response using an integrated microfluidics-matrix assisted laser desorption ionisation/nanoelectrospray ionisation-ion mobility-mass spectrometry platform

Enders, Jeffrey R.; Marasco, Christina C.; Kole, Ayeeshik; Nguyen, Bao; Sevugarajan, S; Seale, Kevin T.; Wikswo, John P.; McLean, John A.

doi:10.1049/iet-syb.2010.0012

Cited by 24 publications

(29 citation statements)

References 60 publications

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“…Although microfluidic devices have greatly improved MS applications, their coupling to DTIMS-MS has been limited to only a few applications in protein/ligand binding (142) and real-time cellular studies (143, 144). The McLean group (143, 144) was the first to couple a mul-titrap nanophysiometer (MTNP) microfluidic device to TWIMS-MS in 2010.…”

Section: Microfluidics-drift Tube Ion Mobility Spectrometry–mass Specmentioning

confidence: 99%

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Coupling Front-End Separations, Ion Mobility Spectrometry, and Mass Spectrometry For Enhanced Multidimensional Biological and Environmental Analyses

Zheng

Wojcik

Zhang

et al. 2017

Annual Rev. Anal. Chem.

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Ion mobility spectrometry (IMS) is a widely used analytical technique for rapid molecular separations in the gas phase. Though IMS alone is useful, its coupling with mass spectrometry (MS) and front-end separations is extremely beneficial for increasing measurement sensitivity, peak capacity of complex mixtures, and the scope of molecular information available from biological and environmental sample analyses. In fact, multiple disease screening and environmental evaluations have illustrated that the IMS-based multidimensional separations extract information that cannot be acquired with each technique individually. This review highlights three-dimensional separations using IMS-MS in conjunction with a range of front-end techniques, such as gas chromatography, supercritical fluid chromatography, liquid chromatography, solid-phase extractions, capillary electrophoresis, field asymmetric ion mobility spectrometry, and microfluidic devices. The origination, current state, various applications, and future capabilities of these multidimensional approaches are described in detail to provide insight into their uses and benefits.

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Section: Microfluidics-drift Tube Ion Mobility Spectrometry–mass Specmentioning

confidence: 99%

“…The McLean group (143, 144) was the first to couple a mul-titrap nanophysiometer (MTNP) microfluidic device to TWIMS-MS in 2010. MTNP is used as a miniature reactor to study the real-time response of small cellular amounts to drugs and other perturbations.…”

Section: Microfluidics-drift Tube Ion Mobility Spectrometry–mass Specmentioning

confidence: 99%

Coupling Front-End Separations, Ion Mobility Spectrometry, and Mass Spectrometry For Enhanced Multidimensional Biological and Environmental Analyses

Zheng

Wojcik

Zhang

et al. 2017

Annual Rev. Anal. Chem.

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“…Obvious future extensions of the technique include its use with other mesenchymal cells and with CMs derived from the hiPSCs from both normal subjects and patients with cardiac disease, and fluorescent measurements of AP propagation along the fiber and the associated Ca 2+ signals [69]. The small volume of fluid surrounding the ECTC is ideal for electrochemical measurements of glucose and lactate fluxes, oxygen consumption and acidification [70], and mass spectrometric measurements of cardiac metabolomics [71]. …”

Section: Resultsmentioning

confidence: 99%

I-Wire Heart-on-a-Chip I: Three-dimensional cardiac tissue constructs for physiology and pharmacology

et al. 2017

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Engineered 3D cardiac tissue constructs (ECTCs) can replicate complex cardiac physiology under normal and pathological conditions. Currently, most measurements of ECTC contractility are either made isometrically, with fixed length and without control of the applied force, or auxotonically against a variable force, with the length changing during the contraction. The “I-Wire” platform addresses the unmet need to control the force applied to ECTCs while interrogating their passive and active mechanical and electrical characteristics. A six-well plate with inserted PDMS casting molds containing neonatal rat cardiomyocytes cultured with fibrin for 13–15 days is mounted on the motorized mechanical stage of an inverted microscope equipped with a fast sCMOS camera. A calibrated flexible probe provides strain load of the ECTC via lateral displacement, and the microscope detects the deflections of both the probe and the ECTC. The ECTCs exhibited longitudinally aligned cardiomyocytes with well-developed sarcomeric structure, recapitulated the Frank-Starling force-tension relationship, and demonstrated expected transmembrane action potentials, electrical and mechanical restitutions, and responses to both β-adrenergic stimulation and blebbistatin. The I-Wire platform enables creation and mechanical and electrical characterization of ECTCs, and hence can be valuable in the study of cardiac diseases, drug screening, drug development, and the qualification of cells for tissue-engineered regenerative medicine.

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“…We are currently developing the substantial experimental hardware and algorithms required to allow the EEA to conduct wet-lab experiments on yeast and other biochemical systems [53, 82]. A fascinating possibility would be to add near-real-time measurements of the transcriptome into robot metabolic scientists by measuring the expression of selected genes through optical detection of green fluorescent protein (GFP) markers.…”

Section: Discussionmentioning

confidence: 99%

Automated refinement and inference of analytical models for metabolic networks

et al. 2011

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The reverse engineering of metabolic networks from experimental data is traditionally a labor-intensive task requiring a priori systems knowledge. Using a proven model as a test system, we demonstrate an automated method to simplify this process by modifying an existing or related model – suggesting nonlinear terms and structural modifications – or even constructing a new model that agrees with the system’s time-series observations. In certain cases, this method can identify the full dynamical model from scratch without prior knowledge or structural assumptions. The algorithm selects between multiple candidate models by designing experiments to make their predictions disagree. We performed computational experiments to analyze a nonlinear seven-dimensional model of yeast glycolytic oscillations. This approach corrected mistakes reliably in both approximated and overspecified models. The method performed well to high levels of noise for most states, could identify the correct model de novo, and make better predictions than ordinary parametric regression and neural network models. We identified an invariant quantity in the model, which accurately derived kinetics and the numerical sensitivity coefficients of the system. Finally, we compared the system to dynamic flux estimation and discussed the scaling and application of this methodology to automated experiment design and control in biological systems in real-time.

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Towards monitoring real-time cellular response using an integrated microfluidics-matrix assisted laser desorption ionisation/nanoelectrospray ionisation-ion mobility-mass spectrometry platform

Cited by 24 publications

References 60 publications

Coupling Front-End Separations, Ion Mobility Spectrometry, and Mass Spectrometry For Enhanced Multidimensional Biological and Environmental Analyses

Coupling Front-End Separations, Ion Mobility Spectrometry, and Mass Spectrometry For Enhanced Multidimensional Biological and Environmental Analyses

I-Wire Heart-on-a-Chip I: Three-dimensional cardiac tissue constructs for physiology and pharmacology

Automated refinement and inference of analytical models for metabolic networks

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