scholarly journals Continuous detection of glucose and insulin in live animals

2020 ◽  
Author(s):  
Mahla Poudineh ◽  
Caitlin L. Maikawa ◽  
Eric Yue Ma ◽  
Jing Pan ◽  
Dan Mamerow ◽  
...  

AbstractReal-time biosensors that can continuously measure circulating biomolecules in vivo would provide valuable insights into a patients’ health status and their response to therapeutics even when there is considerable variability in pharmacokinetics and pharmacodynamics across patient populations. Unfortunately, current real-time biosensors are limited to a handful of analytes (e.g. glucose and blood oxygen) and are limited in sensitivity (high nanomolar). In this work, we describe a general approach for continuously and simultaneously measuring multiple analytes with picomolar sensitivity and sub-second temporal resolution. As exemplars, we report the simultaneous detection of glucose and insulin at picomolar concentrations in live diabetic rats. Using our system, we demonstrate the capacity to resolve inter-individual differences in the pharmacokinetic responses to insulin and discriminate profiles from different insulin formulations at a high temporal resolution. Critically, our approach is general and could be readily modified to continuously and simultaneously measure other circulating analytes in vivo by swapping the affinity reagents, thus making it a versatile tool for biomedical research.

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Nicolette Driscoll ◽  
Richard E. Rosch ◽  
Brendan B. Murphy ◽  
Arian Ashourvan ◽  
Ramya Vishnubhotla ◽  
...  

AbstractNeurological disorders such as epilepsy arise from disrupted brain networks. Our capacity to treat these disorders is limited by our inability to map these networks at sufficient temporal and spatial scales to target interventions. Current best techniques either sample broad areas at low temporal resolution (e.g. calcium imaging) or record from discrete regions at high temporal resolution (e.g. electrophysiology). This limitation hampers our ability to understand and intervene in aberrations of network dynamics. Here we present a technique to map the onset and spatiotemporal spread of acute epileptic seizures in vivo by simultaneously recording high bandwidth microelectrocorticography and calcium fluorescence using transparent graphene microelectrode arrays. We integrate dynamic data features from both modalities using non-negative matrix factorization to identify sequential spatiotemporal patterns of seizure onset and evolution, revealing how the temporal progression of ictal electrophysiology is linked to the spatial evolution of the recruited seizure core. This integrated analysis of multimodal data reveals otherwise hidden state transitions in the spatial and temporal progression of acute seizures. The techniques demonstrated here may enable future targeted therapeutic interventions and novel spatially embedded models of local circuit dynamics during seizure onset and evolution.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Azadeh Mohtashamdolatshahi ◽  
Harald Kratz ◽  
Olaf Kosch ◽  
Ralf Hauptmann ◽  
Nicola Stolzenburg ◽  
...  

Abstract Magnetic Particle Imaging (MPI) is a new imaging modality, which maps the distribution of magnetic nanoparticles (MNP) in 3D with high temporal resolution. It thus may be suited for cardiovascular imaging. Its sensitivity and spatial resolution critically depend on the magnetic properties of MNP. Therefore, we used novel multicore nanoparticles (MCP 3) for in-vivo MPI in rats and analyzed dose requirements, sensitivity and detail resolution. 8 rats were examined using a preclinical MPI scanner (Bruker Biospin GmbH, Germany) equipped with a separate receive coil. MCP 3 and Resovist were administered intravenously (i.v.) into the rats’ tail veins at doses of 0.1, 0.05 and 0.025 mmol Fe/kg followed by serial MPI acquisition with a temporal resolution of 46 volumes per second. Based on a qualitative visual scoring system MCP 3–MPI images showed a significantly (P ≤ 0.05) higher image quality than Resovist-MPI images. Morphological features such as vessel lumen diameters (DL) of the inferior vena cava (IVC) and abdominal aorta (AA) could be assessed along a 2-cm segment in mesenteric area only after administration of MCP 3 at dosages of 0.1, 0.05 mmol Fe/kg. The mean DL ± SD estimated was 2.7 ± 0.6 mm for IVC and 2.4 ± 0.7 mm for AA. Evaluation of DL of the IVC and AA was not possible in Resovist-MPI images. Our results show, that MCP 3 provide better image quality at a lower dosage than Resovist. MCP 3-MPI with a clinically acceptable dose of 0.05 mmol Fe/kg increased the visibility of vessel lumens compared to Resovist-based MPI towards possible detection of vascular abnormalities such as stenosis or aneurysms, in vivo.


2018 ◽  
Author(s):  
Barbara Herbstritt ◽  
Benjamin Gralher ◽  
Markus Weiler

Abstract. The isotopic composition of throughfall is affected by complex exchange, enrichment, and mixing processes in the tree canopy. All interception processes occur simultaneously in space and time generating a complex pattern of throughfall in amount and isotopic composition. This pattern ultimately cascades through the entire hydrologic system and is therefore crucial for studies in catchment hydrology where recharge areas are often forested while reference meteorological stations are generally in the open. For the quasi real-time observation of the isotopic composition of both gross precipitation and throughfall we developed an approach combining an off-the-shelf membrane contactor (Membrana) with a laser-based Cavity Ring-Down Spectrometer (CRDS, Picarro), obtaining isotope readings every two seconds. For the continuous observation of the temporal effect of interception processes two setups with two CRDS instruments in parallel were used analysing gross precipitation and throughfall simultaneously. All devices were kept small to minimize dead volume and thereby, with time-lags of only four minutes, to increase the temporal resolution of isotope observations. Complementarily, meteorological variables were recorded in high temporal resolution at the same location. Comparing these high temporally resolved continuous measurements with discrete liquid or event-based bulk samples, this approach proves to be a powerful tool towards more insight in the very dynamic processes contributing to interception during rainfall events.


2019 ◽  
Vol 2 (1) ◽  
pp. 7 ◽  
Author(s):  
Francesco Giardini ◽  
Valentina Biasci ◽  
Marina Scardigli ◽  
Francesco S. Pavone ◽  
Gil Bub ◽  
...  

Optogenetics is an emerging method that uses light to manipulate electrical activity in excitable cells exploiting the interaction between light and light-sensitive depolarizing ion channels, such as channelrhodopsin-2 (ChR2). Initially used in the neuroscience, it has been adopted in cardiac research where the expression of ChR2 in cardiac preparations allows optical pacing, resynchronization and defibrillation. Recently, optogenetics has been leveraged to manipulate cardiac electrical activity in the intact heart in real-time. This new approach was applied to simulate a re-entrant circuit across the ventricle. In this technical note, we describe the development and the implementation of a new software package for real-time optogenetic intervention. The package consists of a single LabVIEW program that simultaneously captures images at very high frame rates and delivers precisely timed optogenetic stimuli based on the content of the images. The software implementation guarantees closed-loop optical manipulation at high temporal resolution by processing the raw data in workstation memory. We demonstrate that this strategy allows the simulation of a ventricular tachycardia with high stability and with a negligible loss of data with a temporal resolution of up to 1 ms.


2020 ◽  
Vol 318 (5) ◽  
pp. H1091-H1099 ◽  
Author(s):  
Shyue-An Chan ◽  
Marmar Vaseghi ◽  
Nicholas Kluge ◽  
Kalyanam Shivkumar ◽  
Jeffrey L. Ardell ◽  
...  

The sympathetic nervous system modulates cardiac function by controlling key parameters such as chronotropy and inotropy. Sympathetic control of ventricular function occurs through extrinsic innervation arising from the stellate ganglia and thoracic sympathetic chain. In the healthy heart, sympathetic release of norepinephrine (NE) results in positive modulation of chronotropy, inotropy, and dromotropy, significantly increasing cardiac output. However, in the setting of myocardial infarction or injury, sympathetic activation persists, contributing to heart failure and increasing the risk of arrhythmias, including sudden cardiac death. Methodologies for detection of norepinephrine in cardiac tissue are limited. Present techniques rely on microdialysis for analysis by high-performance liquid chromatography coupled to electrochemical detection (HPLC-ED), radioimmunoassay, or other immunoassays, such as enzyme-linked immunosorbent assay (ELISA). Although significant information about the release and action of norepinephrine has been obtained with these methodologies, they are limited in temporal resolution, require large sample volumes, and provide results with a significant delay after sample collection (hours to weeks). In this study, we report a novel approach for measurement of interstitial cardiac norepinephrine, using minimally invasive, electrode-based, fast-scanning cyclic voltammetry (FSCV) applied in a beating porcine heart. The first multispatial and high temporal resolution, multichannel measurements of NE release in vivo are provided. Our data demonstrate rapid changes in interstitial NE profiles with regional differences in response to coronary ischemia, sympathetic nerve stimulation, and alterations in preload/afterload. NEW & NOTEWORTHY Pharmacological, electrical, or surgical regulation of sympathetic neuronal control can be used to modulate cardiac function and treat arrhythmias. However, present methods for monitoring sympathetic release of norepinephrine in the heart are limited in spatial and temporal resolution. Here, we provide for the first time a methodology and demonstration of practice and rapid measures of individualized regional autonomic neurotransmitter levels in a beating heart. We show dynamic, spatially resolved release profiles under normal and pathological conditions.


2012 ◽  
Vol 70 (3) ◽  
pp. 785-790 ◽  
Author(s):  
Varsha Jain ◽  
Jeremy Magland ◽  
Michael Langham ◽  
Felix W. Wehrli

Author(s):  
Iris Haberkorn ◽  
Cosima L. Off ◽  
Michael D. Besmer ◽  
Leandro Buchmann ◽  
Alexander Mathys

Microalgae are emerging as a next-generation biotechnological production system in the pharmaceutical, biofuel, and food domain. The economization of microalgal biorefineries remains a main target, where culture contamination and prokaryotic upsurge are main bottlenecks to impair culture stability, reproducibility, and consequently productivity. Automated online flow cytometry (FCM) is gaining momentum as bioprocess optimization tool, as it allows for spatial and temporal landscaping, real-time investigations of rapid microbial processes, and the assessment of intrinsic cell features. So far, automated online FCM has not been applied to microalgal ecosystems but poses a powerful technology for improving the feasibility of microalgal feedstock production through in situ, real-time, high-temporal resolution monitoring. The study lays the foundations for an application of automated online FCM implying far-reaching applications to impel and facilitate the implementation of innovations targeting at microalgal bioprocesses optimization. It shows that emissions collected on the FL1/FL3 fluorescent channels, harnessing nucleic acid staining and chlorophyll autofluorescence, enable a simultaneous assessment (quantitative and diversity-related) of prokaryotes and industrially relevant phototrophic Chlorella vulgaris in mixed ecosystems of different complexity over a broad concentration range (2.2–1,002.4 cells ⋅μL–1). Automated online FCM combined with data analysis relying on phenotypic fingerprinting poses a powerful tool for quantitative and diversity-related population dynamics monitoring. Quantitative data assessment showed that prokaryotic growth phases in engineered and natural ecosystems were characterized by different growth speeds and distinct peaks. Diversity-related population monitoring based on phenotypic fingerprinting indicated that prokaryotic upsurge in mixed cultures was governed by the dominance of single prokaryotic species. Automated online FCM is a powerful tool for microalgal bioprocess optimization owing to its adaptability to myriad phenotypic assays and its compatibility with various cultivation systems. This allows advancing bioprocesses associated with both microalgal biomass and compound production. Hence, automated online FCM poses a viable tool with applications across multiple domains within the biobased sector relying on single cell–based value chains.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wei Chen ◽  
Ryan G. Natan ◽  
Yuhan Yang ◽  
Shih-Wei Chou ◽  
Qinrong Zhang ◽  
...  

AbstractStudying neuronal activity at synapses requires high spatiotemporal resolution. For high spatial resolution in vivo imaging at depth, adaptive optics (AO) is required to correct sample-induced aberrations. To improve temporal resolution, Bessel focus has been combined with two-photon fluorescence microscopy (2PFM) for fast volumetric imaging at subcellular lateral resolution. To achieve both high-spatial and high-temporal resolution at depth, we develop an efficient AO method that corrects the distorted wavefront of Bessel focus at the objective focal plane and recovers diffraction-limited imaging performance. Applying AO Bessel focus scanning 2PFM to volumetric imaging of zebrafish larval and mouse brains down to 500 µm depth, we demonstrate substantial improvements in the sensitivity and resolution of structural and functional measurements of synapses in vivo. This enables volumetric measurements of synaptic calcium and glutamate activity at high accuracy, including the simultaneous recording of glutamate activity of apical and basal dendritic spines in the mouse cortex.


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