A Robotic Tool for Magnetic Micromanipulation of Cells in the Presence of an Ambient Fluid Flow

2019 ◽  
Author(s):  
Dharmveer Agarwal ◽  
Ajay D. Thakur ◽  
Atul Thakur
Keyword(s):  
Fluid Flow ◽  
Pulse Width Modulation ◽  
Ambient Fluid ◽  
Electromagnetic Coils ◽  
Planning Algorithm ◽  
On Chip ◽  
Automated Feedback ◽  
Robotic Tool ◽  
Proportional Controller

Abstract This paper reports an automated image-guided microrobotic tool to perform nonprehensile magnetic manipulation of large (of the order of few hundreds of microns) microscopic biological objects in the presence of an ambient fluid flow. The developed tool comprises of ferromagnetic microrobots actuated by electromagnetic coils arranged in a quadrupole configuration, a DC power source, and a pulse width modulation (PWM) based controller to vary the coil currents. In order to accomplish the stated objective of automated micromanipulation task, a two-tier approach is adopted, namely, (1) generation of a feedback planning algorithm that invokes one of the two motion maneuvers, namely, ‘arrest’ and ‘move’ and (2) development of a proportional controller that determines the currents to be passed through the coils based on the maneuver invoked so that the resultant magnetic field actuates the ferromagnetic microrobot in the desired direction. A physical experiment was conducted and reported to authenticate the validity of the developed approach. We believe that the developed tool can be used to perform automated feedback controlled micromanipulation of large biological cells and cell aggregates in the presence of an ambient fluid flow especially in in-vivo environments. The inherent biocompatibility of the microbot material provides a possibility to functionalize it with living cells and/or appropriate chemicals rendering it feasible to implement drug delivery and also perform on-chip biological experiments.

scholarly journals Bioengineered Islet Cell Transplantation

2021 ◽  
Author(s):  
Kevin Bellofatto ◽  
Beat Moeckli ◽  
Charles-Henri Wassmer ◽  
Margaux Laurent ◽  
Graziano Oldani ◽  
...  
Keyword(s):  
State Of The Art ◽  
Diabetes Research ◽  
Islet Cell Transplantation ◽  
Β Cell ◽  
Cell Compartment ◽  
Factors Affecting ◽  
Insulin Activity ◽  
On Chip

Abstract Purpose of Review β cell replacement via whole pancreas or islet transplantation has greatly evolved for the cure of type 1 diabetes. Both these strategies are however still affected by several limitations. Pancreas bioengineering holds the potential to overcome these hurdles aiming to repair and regenerate β cell compartment. In this review, we detail the state-of-the-art and recent progress in the bioengineering field applied to diabetes research. Recent Findings The primary target of pancreatic bioengineering is to manufacture a construct supporting insulin activity in vivo. Scaffold-base technique, 3D bioprinting, macro-devices, insulin-secreting organoids, and pancreas-on-chip represent the most promising technologies for pancreatic bioengineering. Summary There are several factors affecting the clinical application of these technologies, and studies reported so far are encouraging but need to be optimized. Nevertheless pancreas bioengineering is evolving very quickly and its combination with stem cell research developments can only accelerate this trend.

scholarly journals Transcriptome comparisons of in vitro intestinal epithelia grown under static and microfluidic gut-on-chip conditions with in vivo human epithelia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kornphimol Kulthong ◽  
Guido J. E. J. Hooiveld ◽  
Loes Duivenvoorde ◽  
Ignacio Miro Estruch ◽  
Victor Marin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Culture Conditions ◽  
Gene Set Enrichment Analysis ◽  
Shear Stresses ◽  
Static Culture ◽  
Dynamic Culture ◽  
Intestinal Segments ◽  
On Chip

AbstractGut-on-chip devices enable exposure of cells to a continuous flow of culture medium, inducing shear stresses and could thus better recapitulate the in vivo human intestinal environment in an in vitro epithelial model compared to static culture methods. We aimed to study if dynamic culture conditions affect the gene expression of Caco-2 cells cultured statically or dynamically in a gut-on-chip device and how these gene expression patterns compared to that of intestinal segments in vivo. For this we applied whole genome transcriptomics. Dynamic culture conditions led to a total of 5927 differentially expressed genes (3280 upregulated and 2647 downregulated genes) compared to static culture conditions. Gene set enrichment analysis revealed upregulated pathways associated with the immune system, signal transduction and cell growth and death, and downregulated pathways associated with drug metabolism, compound digestion and absorption under dynamic culture conditions. Comparison of the in vitro gene expression data with transcriptome profiles of human in vivo duodenum, jejunum, ileum and colon tissue samples showed similarities in gene expression profiles with intestinal segments. It is concluded that both the static and the dynamic gut-on-chip model are suitable to study human intestinal epithelial responses as an alternative for animal models.

scholarly journals O23: CHARACTERISING PATIENT-DERIVED COLORECTAL CANCER TISSUE-ORIGINATED ORGANOIDAL SPHEROIDS FOR HIGH-THROUGHPUT MICROFLUIDIC APPLICATIONS

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
MI Khot ◽  
M Levenstein ◽  
R Coppo ◽  
J Kondo ◽  
M Inoue ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fluid Flow ◽  
High Throughput ◽  
Microfluidic Devices ◽  
In Vitro Models ◽  
Fluorescent Imaging ◽  
Cancer Tissue ◽  
Cell Models

Abstract Introduction Three-dimensional (3D) cell models have gained reputation as better representations of in vivo cancers as compared to monolayered cultures. Recently, patient tumour tissue-derived organoids have advanced the scope of complex in vitro models, by allowing patient-specific tumour cultures to be generated for developing new medicines and patient-tailored treatments. Integrating 3D cell and organoid culturing into microfluidics, can streamline traditional protocols and allow complex and precise high-throughput experiments to be performed with ease. Method Patient-derived colorectal cancer tissue-originated organoidal spheroids (CTOS) cultures were acquired from Kyoto University, Japan. CTOS were cultured in Matrigel and stem-cell media. CTOS were treated with 5-fluorouracil and cytotoxicity evaluated via fluorescent imaging and ATP assay. CTOS were embedded, sectioned and subjected to H&E staining and immunofluorescence for ABCG2 and Ki67 proteins. HT29 colorectal cancer spheroids were produced on microfluidic devices using cell suspensions and subjected to 5-fluorouracil treatment via fluid flow. Cytotoxicity was evaluated through fluorescent imaging and LDH assay. Result 5-fluorouracil dose-dependent reduction in cell viability was observed in CTOS cultures (p<0.01). Colorectal CTOS cultures retained the histology, tissue architecture and protein expression of the colonic epithelial structure. Uniform 3D HT29 spheroids were generated in the microfluidic devices. 5-fluorouracil treatment of spheroids and cytotoxic analysis was achieved conveniently through fluid flow. Conclusion Patient-derived CTOS are better complex models of in vivo cancers than 3D cell models and can improve the clinical translation of novel treatments. Microfluidics can streamline high-throughput screening and reduce the practical difficulties of conventional organoid and 3D cell culturing. Take-home message Organoids are the most advanced in vitro models of clinical cancers. Microfluidics can streamline and improve traditional laboratory experiments.

Overview of existing in vitro BBB models: advantages and disadvantages, current state and future prospects

2021 ◽  
Vol 10 (3) ◽  
pp. 109-120
Author(s):  
A. I. Mosiagina ◽  
A. V. Morgun ◽  
A. B. Salmina
Keyword(s):  
Neurovascular Unit ◽  
Clinical Trial Data ◽  
Advantages And Disadvantages ◽  
The Central Nervous System ◽  
Complex Relationships ◽  
On Chip ◽  
Induced Pluripotent ◽  
Level Of Understanding

There is growing research focusing on endothelial cells as separate units of the blood-brain barrier (BBB), and on the complex relationships between different types of cells within a neurovascular unit. To conduct this type of studies, researches use vastly different in vitro BBB models. The main objective of such models is to study the BBB permeability for different molecules, and to advance the current level of understanding the mechanisms of disease and to develop methods of targeted therapy for the central nervous system. The analysis of the existing Abstract in vitro BBB models and their advantages/disadvantages was conducted using the clinical trial data obtained in Russian/foreign countries. In this review, the authors highlight the most relevant assessment parameters and propose a unified classification of in vitro BBB models. According to the performed analysis, there is a tendency to move from 2D BBB models based on semipermeable inserts to 3D BBB spheroid and microfluidic organ-on-chip models. Moreover, the use of human induced pluripotent stem cells instead of animal primary cells will make it possible to reliably scale the results obtained in vitro to conditions in vivo.

scholarly journals Using a Common Average Reference to Improve Cortical Neuron Recordings From Microelectrode Arrays

2009 ◽  
Vol 101 (3) ◽  
pp. 1679-1689 ◽  
Author(s):  
Kip A. Ludwig ◽  
Rachel M. Miriani ◽  
Nicholas B. Langhals ◽  
Michael D. Joseph ◽  
David J. Anderson ◽  
...  
Keyword(s):  
Signal To Noise Ratio ◽  
Reference Electrode ◽  
Sprague Dawley ◽  
Average Reference ◽  
Markov Theorem ◽  
Sprague Dawley Rats ◽  
On Chip ◽  
Mathematical Justification ◽  
Signal Sources

In this study, we propose and evaluate a technique known as common average referencing (CAR) to generate a more ideal reference electrode for microelectrode recordings. CAR is a computationally simple technique, and therefore amenable to both on-chip and real-time applications. CAR is commonly used in EEG, where it is necessary to identify small signal sources in very noisy recordings. To study the efficacy of common average referencing, we compared CAR to both referencing with a stainless steel bone-screw and a single microelectrode site. Data consisted of in vivo chronic recordings in anesthetized Sprague-Dawley rats drawn from prior studies, as well as previously unpublished data. By combining the data from multiple studies, we generated and analyzed one of the more comprehensive chronic neural recording datasets to date. Reference types were compared in terms of noise level, signal-to-noise ratio, and number of neurons recorded across days. Common average referencing was found to drastically outperform standard types of electrical referencing, reducing noise by >30%. As a result of the reduced noise floor, arrays referenced to a CAR yielded almost 60% more discernible neural units than traditional methods of electrical referencing. CAR should impart similar benefits to other microelectrode recording technologies—for example, chemical sensing—where similar differential recording concepts apply. In addition, we provide a mathematical justification for CAR using Gauss-Markov theorem and therefore help place the application of CAR into a theoretical context.

In Vitro Experimental Investigation of the Integrity of the Stem–Cement Interface

2013 ◽  
Vol 647 ◽  
pp. 53-56
Author(s):  
Hong Yu Zhang ◽  
Leigh Fleming ◽  
Liam Blunt
Keyword(s):  
Experimental Investigation ◽  
Fluid Flow ◽  
Hip Replacement ◽  
Hip Prosthesis ◽  
Vitro Experiment ◽  
Cement Interface ◽  
In Vitro Experiment ◽  
Mechanical Bonding

The rationale behind failure of cemented total hip replacement is still far from being well understood in a mechanical and molecular perspective. In the present study, the integrity of the stem–cement interface was investigated through an in vitro experiment monitoring fluid flow along this interface. The results indicated that a good mechanical bonding formed at the stem–cement interface before debonding of this interface was induced by physiological loadings during the in vivo service of the hip prosthesis.

scholarly journals On-chip immobilization of planarians for in vivo imaging

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Joseph P. Dexter ◽  
Mary B. Tamme ◽  
Christine H. Lind ◽  
Eva-Maria S. Collins
Keyword(s):  
In Vivo Imaging ◽  
On Chip
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