scholarly journals Electrochemical mapping of oxygenation in the three-dimensional multicellular tumour hemi-spheroid

2019 ◽  
Vol 475 (2225) ◽  
pp. 20180647 ◽  
Author(s):  
Disha B. Sheth ◽  
Miklόs Gratzl
Keyword(s):  
Cancer Biology ◽  
Normal Tissue ◽  
Microelectrode Array ◽  
Three Dimensional ◽  
Blood Capillaries ◽  
Drug Molecules ◽  
Tumour Spheroid ◽  
Lethal Level ◽  
Drug Concentrations

Blood capillaries deliver oxygen and nutrients to surrounding micro-regions of tissue and carry away metabolic waste. In normal tissue, capillaries are close enough to keep all the cells viable. In solid tumours, the capillary system is chaotic and typical inter-capillary distances are larger than in normal tissue. Therefore, hypoxic regions develop. Drug molecules may not reach these areas at concentrations above the lethal level. The combined effect of low drug concentrations and local hypoxia, often exacerbated by acidity, leads to therapy failure. To better understand the interplay between hypoxia and poor drug penetration, oxygenation needs to be assessed in different areas of inter-capillary tissue. The multicellular tumour spheroid is a well-established three-dimensional (3D) in vitro model of the capillary microenvironment. It is used to mimic nascent tumours and micro-metastases as well. In this work, we demonstrate for the first time that dynamic intra-spheroidal oxygen maps can be obtained at the 3D multicellular tumour hemi-spheroid (MCH) using a non-invasive microelectrode array. The same oxygen distributions exist inside the equivalent but less accessible full spheroid. The MCH makes high throughput—high content analysis of spheroids feasible and thus can assist studies on basic cancer biology, drug development and personalized medicine.

3D Culture Modelling: An Emerging Approach for Translational Cancer Research in Sarcomas

2020 ◽  
Vol 27 (29) ◽  
pp. 4778-4788 ◽  
Author(s):  
Victoria Heredia-Soto ◽  
Andrés Redondo ◽  
José Juan Pozo Kreilinger ◽  
Virginia Martínez-Marín ◽  
Alberto Berjón ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Cancer Biology ◽  
Soft Tissues ◽  
Three Dimensional ◽  
3D Culture ◽  
Resistance Mechanisms ◽  
In Vitro Models ◽  
Tumour Spheroids ◽  
Current Therapies

Sarcomas are tumours of mesenchymal origin, which can arise in bone or soft tissues. They are rare but frequently quite aggressive and with a poor outcome. New approaches are needed to characterise these tumours and their resistance mechanisms to current therapies, responsible for tumour recurrence and treatment failure. This review is focused on the potential of three-dimensional (3D) in vitro models, including multicellular tumour spheroids (MCTS) and organoids, and the latest data about their utility for the study on important properties for tumour development. The use of spheroids as a particularly valuable alternative for compound high throughput screening (HTS) in different areas of cancer biology is also discussed, which enables the identification of new therapeutic opportunities in commonly resistant tumours.

scholarly journals 3D high-density microelectrode array with optical stimulation and drug delivery for investigating neural circuit dynamics

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hyogeun Shin ◽  
Sohyeon Jeong ◽  
Ju-Hyun Lee ◽  
Woong Sun ◽  
Nakwon Choi ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Microelectrode Array ◽  
Neural Circuit ◽  
Three Dimensional ◽  
Brain Dysfunction ◽  
High Density ◽  
Optical Stimulation ◽  
Functional Connections ◽  
Neural Activities

AbstractInvestigation of neural circuit dynamics is crucial for deciphering the functional connections among regions of the brain and understanding the mechanism of brain dysfunction. Despite the advancements of neural circuit models in vitro, technologies for both precisely monitoring and modulating neural activities within three-dimensional (3D) neural circuit models have yet to be developed. Specifically, no existing 3D microelectrode arrays (MEAs) have integrated capabilities to stimulate surrounding neurons and to monitor the temporal evolution of the formation of a neural network in real time. Herein, we present a 3D high-density multifunctional MEA with optical stimulation and drug delivery for investigating neural circuit dynamics within engineered 3D neural tissues. We demonstrate precise measurements of synaptic latencies in 3D neural networks. We expect our 3D multifunctional MEA to open up opportunities for studies of neural circuits through precise, in vitro investigations of neural circuit dynamics with 3D brain models.

Imitating Hypoxia and Tumor Microenvironment with Immune Evasion by Employing Three Dimensional in vitro Cellular Models: Impressive Tool in Drug Discovery

2021 ◽  
Vol 16 ◽  
Author(s):  
Suman Kumar Ray ◽  
Sukhes Mukherjee
Keyword(s):  
Cell Culture ◽  
Tumor Microenvironment ◽  
Immune Evasion ◽  
Cancer Biology ◽  
Three Dimensional ◽  
3D Cell Culture ◽  
Cell Culture Techniques ◽  
Culture Techniques ◽  
Hypoxic Tumor

: The heterogeneous tumor microenvironment is exceptionally perplexing and not wholly comprehended. Different multifaceted alignments lead to the generation of oxygen destitute situations within the tumor niche that modulate numerous intrinsic tumor microenvironments. Disentangling these communications is vital for scheming practical therapeutic approaches that can successfully decrease tumor allied chemotherapy resistance by utilizing the innate capability of the immune system. Several research groups have concerned with a protruding role for oxygen metabolism along with hypoxia in the immunity of healthy tissue. Hypoxia in addition to hypoxia-inducible factors (HIFs) in the tumor microenvironment plays an important part in tumor progression and endurance. Although numerous hypoxia-focused therapies have shown promising outcomes both in vitro and in vivo these outcomes have not effectively translated into clinical preliminaries. Distinctive cell culture techniques have utilized as an in vitro model for tumor niche along with tumor microenvironment and proficient in more precisely recreating tumor genomic profiles as well as envisaging therapeutic response. To study the dynamics of tumor immune evasion, three-dimensional (3D) cell cultures are more physiologically important to the hypoxic tumor microenvironment. Recent research has revealed new information and insights into our fundamental understanding of immune systems, as well as novel results that have been established as potential therapeutic targets. There are a lot of patented 3D cell culture techniques which will be highlighted in this review. At present notable 3D cell culture procedures in the hypoxic tumor microenvironment, discourse open doors to accommodate both drug repurposing, advancement, and divulgence of new medications and will deliberate the 3D cell culture methods into standard prescription disclosure especially in the field of cancer biology which will be discussing here.

scholarly journals In situ measurement of ECM rheology and microheterogeneity in embedded and overlaid 3D pancreatic tumor stroma co-cultures via passive particle tracking

2017 ◽  
Vol 10 (06) ◽  
pp. 1742003 ◽  
Author(s):  
Dustin P. Jones ◽  
William Hanna ◽  
Gwendolyn M. Cramer ◽  
Jonathan P. Celli
Keyword(s):  
Mechanical Properties ◽  
Tumor Growth ◽  
Particle Tracking ◽  
Cancer Biology ◽  
Three Dimensional ◽  
Tumor Stroma ◽  
Physical Force ◽  
Culture Models

Tumor growth is regulated by a diverse set of extracellular influences, including paracrine crosstalk with stromal partners, and biophysical interactions with surrounding cells and tissues.Studies elucidating the role of physical force and the mechanical properties of the extracellular matrix (ECM) itself as regulators of tumor growth and invasion have been greatly catalyzed by the use of in vitro three-dimensional (3D) tumor models. These systems provide the ability to systematically isolate, manipulate, and evaluate impact of stromal components and extracellular mechanics in a platform that is both conducive to imaging and biologically relevant. However, recognizing that mechanoregulatory crosstalk is bi-directional and fully utilizing these models requires complementary methods for in situ measurements of the local mechanical environment. Here, in 3D tumor/fibroblast co-culture models of pancreatic cancer, a disease characterized by its prominent stromal involvement, we evaluate the use of particle-tracking microrheology to probe dynamic mechanical changes. Using videos of fluorescently labeled polystyrene microspheres embedded in collagen I ECM, we measure spatiotemporal changes in the Brownian motion of probes to report local ECM shear modulus and microheterogeneity. This approach reveals stiffening of collagen in fibroblast co-cultures relative to cultures with cancer cells only, which exhibit degraded ECM with heterogeneous microstructure. We further show that these effects are dependent on culture geometry with contrasting behavior for embedded and overlay cultures. In addition to potential application to screening stroma-targeted therapeutics, this work also provides insight into how the composition and plating geometry impact the mechanical properties of 3D cell cultures that are increasingly widely used in cancer biology.

scholarly journals 3D Fuzzy Graphene Microelectrode Array for Neurotransmitter Sensing at Sub-cellular Spatial Resolution

2020 ◽  
Author(s):  
Elisa Castagnola ◽  
Raghav Garg ◽  
Sahil Rastogi ◽  
Tzahi Cohen-Karni ◽  
Xinyan Tracy Cui
Keyword(s):  
Surface Area ◽  
Spatial Resolution ◽  
Microelectrode Array ◽  
High Surface ◽  
High Surface Area ◽  
Three Dimensional ◽  
High Sensitivity ◽  
Electrochemical Sensing ◽  
Brain Functions

<div>Dopamine (DA) is a monoamine neurotransmitter involved in the modulation of various physiological brain functions, including learning, motivation, reward, and motor functions. The development of a high sensitivity real-time sensor for multi-site detection of DA with high spatial resolution has critical implications for both neuroscience and clinical communities to improve understanding and treatments of neurological and neuropsychiatric disorders. Here, we present high-surface area out-of-plane grown three-dimensional (3D) fuzzy graphene (3DFG) microelectrode arrays (MEAs) for highly selective, sensitive, and stable DA electrochemical sensing. 3DFG microelectrodes present a remarkable sensitivity to DA (2.87 ± 0.25 nA/nM, with</div><div>LOD of 990±15 pM), the highest reported for nanocarbon MEAs using Fast Scan Cyclic Voltammetry (FSCV). The high surface area of 3DFG allows for miniaturization of electrode down to 2 x 2 μm^2, without compromising the electrochemical performance. Moreover, 3DFG MEAs are electrochemically stable under 7.2 million scans of continuous FSCV cycling, present exceptional selectivity over the most common interferents in vitro with minimum fouling by electrochemical byproducts, and can discriminate DA and serotonin (5-HT) in response to the injection of their 50:50 mixture. These results highlight the potential of 3DFG MEAs as a promising platform for FSCV based multi-site detection of DA with high sensitivity, selectivity, and spatial resolution.</div>

scholarly journals A mesh microelectrode array for non-invasive electrophysiology within neural organoids

2020 ◽  
Author(s):  
Matthew McDonald ◽  
David Sebinger ◽  
Lisa Brauns ◽  
Laura Gonzalez-Cano ◽  
Yotam Menuchin-Lasowski ◽  
...  
Keyword(s):  
Microelectrode Array ◽  
Single Cells ◽  
Three Dimensional ◽  
Microelectrode Arrays ◽  
Polymer Scaffolds ◽  
Neural Models ◽  
New Class ◽  
Non Invasive

AbstractOrganoids are emerging in vitro models of human physiology. Neural models require the evaluation of functional activity of single cells and networks, which is best measured by microelectrode arrays. The characteristics of organoids clash with existing in vitro or in vivo microelectrode arrays. With inspiration from implantable mesh electronics and growth of organoids on polymer scaffolds, we fabricated suspended hammock-like mesh microelectrode arrays for neural organoids. We have demonstrated the growth of organoids enveloping these meshes, their cultivation for at least nine months, and could measure spontaneous electrical activity within organoids. Our concept should enable a new class of microelectrode arrays for in vitro models of three-dimensional electrically active tissue.

scholarly journals Fabrication of Subretinal 3D Microelectrodes with Hexagonal Arrangement

Micromachines ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 467 ◽  
Author(s):  
Hee Won Seo ◽  
Namju Kim ◽  
Sohee Kim
Keyword(s):  
Integrated Circuit ◽  
Microelectrode Array ◽  
3D Structure ◽  
Three Dimensional ◽  
Active Electrode ◽  
Prosthetic Devices ◽  
In Vivo Experiments ◽  
Hexagonal Arrangement

This study presents the fabrication of three-dimensional (3D) microelectrodes for subretinal stimulation, to accommodate adjacent return electrodes surrounding a stimulating electrode. For retinal prosthetic devices, the arrangement of return electrodes, the electrode size and spacing should be considered together, to reduce the undesired dissipation of electric currents. Here, we applied the hexagonal arrangement to the microelectrode array for the localized activation of retinal cells and better visual acuity. To provide stimuli more efficiently to non-spiking neurons, a 3D structure was created through a customized pressing process, utilizing the elastic property of the materials used in the fabrication processes. The diameter and pitch of the Pt-coated electrodes were 150 μm and 350 μm, respectively, and the height of the protruded electrodes was around 20 μm. The array consisted of 98 hexagonally arranged electrodes, supported by a flexible and transparent polydimethylsiloxane (PDMS) base, with a thickness of 140 μm. Also, the array was coated with 2 μm-thick parylene-C, except the active electrode sites, for more focused stimulation. Finally, the electrochemical properties of the fabricated microelectrodes were characterized, resulting in the mean impedance of 384.87 kΩ at 1 kHz and the charge storage capacity (CSC) of 2.83 mC·cm−2. The fabricated microelectrodes are to be combined with an integrated circuit (IC) for additional in vitro and in vivo experiments.

scholarly journals Bioreactor-Based Tumor Tissue Engineering

Acta Naturae ◽  
2016 ◽  
Vol 8 (3) ◽  
pp. 44-58 ◽  
Author(s):  
A. E. Guller ◽  
P. N. Grebenyuk ◽  
A. B. Shekhter ◽  
A. V. Zvyagin ◽  
S. M. Deyev
Keyword(s):  
Tissue Engineering ◽  
Cancer Biology ◽  
Tumor Tissue ◽  
Three Dimensional ◽  
Culture Conditions ◽  
Laboratory Animals ◽  
Malignant Neoplasms ◽  
Successful Implementation ◽  
Engineering Technology

This review focuses on modeling of cancer tumors using tissue engineering technology. Tumor tissue engineering (TTE) is a new method of three-dimensional (3D) simulation of malignant neoplasms. Design and development of complex tissue engineering constructs (TECs) that include cancer cells, cell-bearing scaffolds acting as the extracellular matrix, and other components of the tumor microenvironment is at the core of this approach. Although TECs can be transplanted into laboratory animals, the specific aim of TTE is the most realistic reproduction and long-term maintenance of the simulated tumor properties in vitro for cancer biology research and for the development of new methods of diagnosis and treatment of malignant neoplasms. Successful implementation of this challenging idea depends on bioreactor technology, which will enable optimization of culture conditions and control of tumor TECs development. In this review, we analyze the most popular bioreactor types in TTE and the emerging applications.

scholarly journals 3D Fuzzy Graphene Microelectrode Array for Neurotransmitter Sensing at Sub-cellular Spatial Resolution

2020 ◽  
Author(s):  
Elisa Castagnola ◽  
Raghav Garg ◽  
Sahil Rastogi ◽  
Tzahi Cohen-Karni ◽  
Xinyan Tracy Cui
Keyword(s):  
Surface Area ◽  
Spatial Resolution ◽  
Microelectrode Array ◽  
High Surface ◽  
High Surface Area ◽  
Three Dimensional ◽  
High Sensitivity ◽  
Electrochemical Sensing ◽  
Brain Functions

<div>Dopamine (DA) is a monoamine neurotransmitter involved in the modulation of various physiological brain functions, including learning, motivation, reward, and motor functions. The development of a high sensitivity real-time sensor for multi-site detection of DA with high spatial resolution has critical implications for both neuroscience and clinical communities to improve understanding and treatments of neurological and neuropsychiatric disorders. Here, we present high-surface area out-of-plane grown three-dimensional (3D) fuzzy graphene (3DFG) microelectrode arrays (MEAs) for highly selective, sensitive, and stable DA electrochemical sensing. 3DFG microelectrodes present a remarkable sensitivity to DA (2.87 ± 0.25 nA/nM, with</div><div>LOD of 990±15 pM), the highest reported for nanocarbon MEAs using Fast Scan Cyclic Voltammetry (FSCV). The high surface area of 3DFG allows for miniaturization of electrode down to 2 x 2 μm^2, without compromising the electrochemical performance. Moreover, 3DFG MEAs are electrochemically stable under 7.2 million scans of continuous FSCV cycling, present exceptional selectivity over the most common interferents in vitro with minimum fouling by electrochemical byproducts, and can discriminate DA and serotonin (5-HT) in response to the injection of their 50:50 mixture. These results highlight the potential of 3DFG MEAs as a promising platform for FSCV based multi-site detection of DA with high sensitivity, selectivity, and spatial resolution.</div>

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