Fabrication of Planar Microelectrode Array Using Laser-Patterned ITO and SU-8

For several decades, microelectrode array (MEA) has been a powerful tool for in vitro neural electrophysiology because it provides a unique approach for monitoring the activity of a number of neurons over time. Due to the various applications of MEAs with different types of cells and tissues, there is an increasing need to customize the electrode designs. However, the fabrication of conventional MEAs requires several microfabrication procedures of deposition, etching, and photolithography. In this study, we proposed a simple fabrication method with a laser-patterned indium tin oxide (ITO) conductor and SU-8 photoresist insulation. Unlike in a conventional metal patterning process, only the outlines of ITO conductors are ablated by laser without removing background ITO. Insulation is achieved simply via SU-8 photolithography. The electrode sites are electroplated with iridium oxide (IrOX) to improve the electrochemical properties. The fabricated MEAs are electrochemically characterized and the stability of insulation is also confirmed by impedance monitoring for three weeks. Dissociated neurons of rat hippocampi are cultured on MEAs to verify the biocompatibility and the capacity for extracellular neural recording. The electrochemical and electrophysiological results with the fabricated MEAs are similar to those from conventional SiNX-insulated MEAs. Therefore, the proposed MEA with laser-patterned ITO and SU-8 is cost-effective and equivalently feasible compared with the conventional MEAs fabricated using thin-film microfabrication techniques.

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Development of Titanium Needle Probes for Neural Recording and Evaluation of Magnetic Resonance Imaging Artifacts

Journal of Nanotechnology in Engineering and Medicine ◽

10.1115/1.4000039 ◽

2009 ◽

Vol 1 (1) ◽

Cited By ~ 4

Author(s):

Hargsoon Yoon ◽

Devesh C. Deshpande ◽

T. H. Kim ◽

Eun-Kee Jeong ◽

Robert E. Harbaugh ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Microelectrode Array ◽

Neural Recording ◽

Iridium Oxide ◽

Resonance Imaging ◽

Needle Probe ◽

Imaging Artifacts ◽

Neural Probe

The aim of this research is to develop a mechanically flexible and strong neural probe with microelectrode array for future clinical applications in neural prosthetics and neurological disorder fields. This research specifically focuses on the development of neural recording electrodes with iridium oxide (IrOx) electrodes on a titanium needle probe and discusses the fabrication techniques and their evaluation for physical properties and electrochemical performance. Microfabrication processes, such as inductive coupled plasma etching, were used to deeply etch the Ti needle structures on titanium foils, and microelectrode arrays with iridium oxide films were formed by electrochemical deposition for low impedance neural recording. Mechanical and electrochemical analyses were performed to verify the viability of Ti needle probes in vitro. The final section of this paper addresses the issue of magnetic resonance imaging artifacts of titanium needle probes, and test results are compared with similarly fabricated Si needle probes. The advantages of using a titanium needle probe are discussed in the application of neural probe electrodes, as well.

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Phenolic Compounds in Calafate Berries Encapsulated by Spray Drying: Neuroprotection Potential into the Ingredient

Antioxidants ◽

10.3390/antiox10111830 ◽

2021 ◽

Vol 10 (11) ◽

pp. 1830

Author(s):

María E. Romero-Román ◽

Mauricio Schoebitz ◽

Jorge Fuentealba ◽

Cristina García-Viguera ◽

María D. López Belchí

Keyword(s):

Spray Drying ◽

Antioxidant Activities ◽

Value Added ◽

Cost Effective ◽

Biological Action ◽

Natural State ◽

Degenerative Disorders ◽

The Stability ◽

Berry Extracts

Calafate is a berry rich in anthocyanins that presents higher content of polyphenols than other fruits. Its compounds have been described previously, however, the potential thereof in preventing and treating degenerative disorders has not yet been studied. Due to its astringency, the consumption of this berry in its natural state is limited. To profit from the aforementioned properties and reduce palatability issues, calafate berry extracts were microencapsulated by spray drying, a rapid, cost-effective and scalable process, and were then compared with freeze drying as a control. The stability of its contents and its in-vitro potential, with respect to AChE activity and neuroprotection, were measured from the obtained microcapsules, resulting from temperature treatments and different encapsulant contents. The results indicated that the spray-dried powders were stable, despite high temperatures, and their encapsulation exhibited nearly 50% efficiency. The highest quantity of polyphenols and 3-O-glycosylated anthocyanins was obtained from encapsulation with 20% maltodextrin, at 120 °C. Temperature did not affect the microcapsules’ biological action, as demonstrated by their antioxidant activities. The prevention of Aβ peptide cytotoxicity in PC12 cells (20%) revealed that encapsulated calafate can confer neuroprotection. We conclude that spray-drying is an appropriate technique for scaling-up and producing new value-added calafate formulations with anti-neurodegenerative effects and vivid colors.

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Hemispherical Microelectrode Array for Ex Vivo Retinal Neural Recording

Micromachines ◽

10.3390/mi11050538 ◽

2020 ◽

Vol 11 (5) ◽

pp. 538 ◽

Cited By ~ 2

Author(s):

Yoonhee Ha ◽

Hyun-Ji Yoo ◽

Soowon Shin ◽

Sang Jun

Keyword(s):

Flexible Electronics ◽

Microelectrode Array ◽

Ex Vivo ◽

Electrode Array ◽

Neural Recording ◽

Electrode Layer ◽

Retinal Tissue ◽

Visual Encoding ◽

Micro Patterns

To investigate the neuronal visual encoding process in the retina, researchers have performed in vitro and ex vivo electrophysiological experiments using animal retinal tissues. The microelectrode array (MEA) has become a key component in retinal experiments because it enables simultaneous neural recording from a population of retinal neurons. However, in most retinal experiments, it is inevitable that the retinal tissue is flattened on the planar MEA, becoming deformed from the original hemispherical shape. During the tissue deforming process, the retina is subjected to mechanical stress, which can induce abnormal physiological conditions. To overcome this problem, in this study, we propose a hemispherical MEA with a curvature that allows retinal tissues to adhere closely to electrodes without tissue deformation. The electrode array is fabricated by stretching a thin, flexible polydimethylsiloxane (PDMS) electrode layer onto a hemispherical substrate. To form micro patterns of electrodes, laser processing is employed instead of conventional thin-film microfabrication processes. The feasibility for neural recording from retinal tissues using this array is shown by conducting ex vivo retinal experiments. We anticipate that the proposed techniques for hemispherical MEAs can be utilized not only for ex vivo retinal studies but also for various flexible electronics.

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Review of the Observations Which Have Accumulated with regard to the Significance of Diphtheria Types in the Last Four Years (1931–1935)

Proceedings of the Royal Society of Medicine ◽

10.1177/003591573602900902 ◽

1936 ◽

Vol 29 (9) ◽

pp. 1029-1054 ◽

Cited By ~ 14

Author(s):

K. E. Cooper ◽

F. C. Happold ◽

J. W. McLeod ◽

H. E. De C. Woodcock ◽

J. S. Anderson ◽

...

Keyword(s):

Cause Of Death ◽

Human Body ◽

Death Rate ◽

Good Deal ◽

Clinical Severity ◽

Adequate Explanation ◽

Nasal Carrier ◽

Different Types ◽

The Stability

In a series of more than 6,000 cases of diphtheria gathered from many parts of the country and from Germany during the last five years, at least 95% of the strains have fallen within three principal types described in 1933 as Gravis, Intermediate, and Mitis. Of these the Gravis strains have been found to be associated with the highest case death-rate and the greatest incidence of paralysis. The Intermediate strains are more nearly related to Gravis than to Mitis in respect of their case death-rate, and at least equal to Gravis in tending to produce hæmorrhagic phenomena. The “Mitis” strains are the most likely of all to produce lesions extending to the larynx and lungs, but apart from such complications are rarely the cause of death. The suggested nomenclature for the types is further justified by observations on the incidence of diphtheria in the immunized and on diphtheria mortality in areas in which different types predominate. Also, it is justified though not so definitely by observations on animal pathogenicity. Typical Gravis strains are so constantly pathogenic to animals that virulence tests with such strains are superfluous. The stability of the types both in the animal and in the human body is marked although a number of observations are extant suggesting fluctuation of type in vitro. It seems most probable, although open to question, that the fluctuations of type observed in many areas over a period of years are due to the waxing and waning of virulence of a number of independent races, rather than to mutations from one to another. The discrepancy between the clinical severity of Gravis infections and their poor capacity to produce toxin in vitro has not yet received any adequate explanation. The nasal carrier is the most important factor in the spread of diphtheria. Clauberg's suggestion that the variants from the three well-defined types which are met may best be explained by rough to smooth variation within the types, the rougher strains representing the more virulent forms in each type, receives a good deal of support from a wide survey of the accumulated observations. A considerable group of freely growing and rough-non-starch fermenting forms which are non-pathogenic would form an exception to this rule as these would be classified as rough “Mitis.” These may, however, eventually prove with further investigation to be diphtheroid strains distinct from “Mitis.”

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Transparent Microelectrode Arrays Fabricated by Ion Beam Assisted Deposition for Neuronal Cell In Vitro Recordings

Micromachines ◽

10.3390/mi11050497 ◽

2020 ◽

Vol 11 (5) ◽

pp. 497 ◽

Cited By ~ 2

Author(s):

Tomi Ryynänen ◽

Ropafadzo Mzezewa ◽

Ella Meriläinen ◽

Tanja Hyvärinen ◽

Jukka Lekkala ◽

...

Keyword(s):

Thin Films ◽

Indium Tin Oxide ◽

Microelectrode Array ◽

Electrode Materials ◽

Ion Beam ◽

Neuronal Cell ◽

Measurement Properties ◽

Ito Thin Films ◽

Sputter Deposited

Microelectrode array (MEA) is a tool used for recording bioelectric signals from electrically active cells in vitro. In this paper, ion beam assisted electron beam deposition (IBAD) has been used for depositing indium tin oxide (ITO) and titanium nitride (TiN) thin films which are applied as transparent track and electrode materials in MEAs. In the first version, both tracks and electrodes were made of ITO to guarantee full transparency and thus optimal imaging capability. In the second version, very thin (20 nm) ITO electrodes were coated with a thin (40 nm) TiN layer to decrease the impedance of Ø30 µm electrodes to one third (1200 kΩ → 320 kΩ) while maintaining (partial) transparency. The third version was also composed of transparent ITO tracks, but the measurement properties were optimized by using thick (200 nm) opaque TiN electrodes. In addition to the impedance, the optical transmission and electric noise levels of all three versions were characterized and the functionality of the MEAs was successfully demonstrated using human pluripotent stem cell-derived neuronal cells. To understand more thoroughly the factors contributing to the impedance, MEAs with higher IBAD ITO thickness as well as commercial sputter-deposited and highly conductive ITO were fabricated for comparison. Even if the sheet-resistance of our IBAD ITO thin films is very high compared to the sputtered one, the impedances of the MEAs of each ITO grade were found to be practically equal (e.g., 300–370 kΩ for Ø30 µm electrodes with 40 nm TiN coating). This implies that the increased resistance of the tracks, either caused by lower thickness or lower conductivity, has hardly any contribution to the impedance of the MEA electrodes. The impedance is almost completely defined by the double-layer interface between the electrode top layer and the medium including cells.

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Drug repositioning: A Unique Approach to Refurbish Drug Discovery

Current Drug Discovery Technologies ◽

10.2174/1570163818666210316114331 ◽

2021 ◽

Vol 18 ◽

Author(s):

Mayura A Kale ◽

Prashant B Shamkuwar ◽

Vishnukant K Mourya ◽

Aishwarya B Deshpande ◽

Priyanka A Shelke

Keyword(s):

Drug Discovery ◽

Drug Repositioning ◽

Cost Effective ◽

Positive Outcomes ◽

Computational Tools ◽

Therapeutic Implications ◽

Novel Drugs ◽

Unique Approach ◽

Approved Drugs

: Since a decade, it has been observed that there is remarkable decrease in the quantum of novel clinically approved drugsin spite of modernization in research and development process. We have highlighted repositioning of drugs as a methodology that has found new therapeutic implications for clinically approved drugs but with different indications. This can be considered as an upbringing strategy to deliver timely and cost-effective solutions which still needexplorationtoget over the shortage of number of novel drugs reaching market. This review focuses on activity-based drug repositioning approach, which is used to explore new uses of known drugs that are already approved for specific indications and are now being used for other indications on the basis ofthe fact that single drug interacts with multiple targets. It also includes current research trends related to drug repositioning which depends on strong knowledge of medicinal chemistry and involves elucidation of mechanisms of action and validation of novel targets. The review highlights theimportance totheusage of computational tools and databases of various forms for drug repositioning purposes which have enhanced the ability to pose reasonable and testable hypotheses. The critical nature of this aspect is obvious in cases where data gathered from in vitro or animal models do not confirm in subsequent clinical trials. Hence, considering positive outcomes of drug repositioning, it can be surmised that this approach can serve as promising one that can develop into a robust drug discovery strategy.

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Biological Modulation of the Treg:Teff Ratio: From Immunosuppression to Immunoactivation

Immunosuppression ◽

10.5772/intechopen.92038 ◽

2020 ◽

Author(s):

Xining Yang ◽

Mark D. Scott

Keyword(s):

T Cell ◽

Autoimmune Diseases ◽

Immune Cells ◽

Cost Effective ◽

Cancer Cell Growth ◽

Unique Approach ◽

A Current

T cell-mediated immunomodulation can be, in simple terms, defined as altering the normal Treg:Teff ratio. Immunosuppression skews the net Treg:Teff ratio toward the ‘tolerogenic’ Treg component, while immunoactivation skews the response toward the ‘proinflammatory’ Teff component. In the treatment of autoimmune diseases, achieving an immunosuppressive state is a desirable goal in order to prevent ongoing injury by activated Teff cells. In contrast, an innate, or induced, immunosuppressive state can be deleterious and prevent pathogen-induced disease while allow for the progression of cancer. Indeed, a current goal of cancer therapy is attenuating an existing endogenous immunosuppressive state that prevents effective T cell-mediated immunorecognition of cancer cells. Thus, the biological modulation of the Treg:Teff ratio provides a unique approach for treating both autoimmune diseases and cancers. Using a biomanufacturing system, miRNA-enriched immunotherapeutic has been generated that either induce (TA1) or overcome (IA1) an immunosuppressive state. As will be shown, these therapeutics show efficacy both in vitro and in vivo in the prevention of autoimmune Type 1 diabetes and in enhancing the ability of resting immune cells to recognize and inhibit cancer cell growth. The successful development of these cost-effective, and easily biomanufactured, secretome-based therapeutics may prove useful in treating both autoimmune diseases and cancer.

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The Effect of Cement Aging on the Stability of a Cement-in-Cement Revision Construct

Applied Sciences ◽

10.3390/app11062814 ◽

2021 ◽

Vol 11 (6) ◽

pp. 2814

Author(s):

Mareike Schonhoff ◽

Therese Bormann ◽

Kevin Knappe ◽

Tobias Reiner ◽

Linda Stange ◽

...

Keyword(s):

Bone Cement ◽

Revision Surgery ◽

Bending Strength ◽

Intraoperative Complications ◽

In Vitro Study ◽

Cement Mantle ◽

Significant Difference ◽

Different Types ◽

The Stability

A revision surgery can be a complicated procedure. The prevention of the removal of a well-integrated cement mantle can minimize intraoperative complications. With the cement-in-cement technique, the implant will be fixated with a layer of bone cement onto the remaining cement mantle. In our experimental in vitro study, we investigated the effect of cement aging of a cement-in-cement revision construct and regular cement mantle on the bending strength. Two different types of bone cement were tested at four different stages of aging. The Palacos cement showed no significant difference in bending strength at any aging point, regardless of whether it was used primarily or as a cement-in-cement revision. In contrast, the SmartSet MV cement showed a significant difference between the primary and cement-in-cement applications depending on cement aging time. The comparison of the two cement-in-cement structures investigated showed significant differences between the manufacturers depending on the cement aging.

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Evaluation of Different Types of Alginate Microcapsules as Bioreactors for Producing Endostatin

Cell Transplantation ◽

10.3727/000000003108746902 ◽

2003 ◽

Vol 12 (4) ◽

pp. 351-364 ◽

Cited By ~ 22

Author(s):

A. M. Rokstad ◽

B. Strand ◽

K. Rian ◽

B. Steinkjer ◽

B. Kulseng ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Lines ◽

Therapeutic Potential ◽

Cost Effective ◽

Stability Studies ◽

Alginate Capsules ◽

Pressure Test ◽

Different Types ◽

The Stability ◽

Therapeutic Substance

The use of nonautologous cell lines producing a therapeutic substance encapsulated within alginate microcapsules could be an alternative way of treating different diseases in a cost-effective way. Malignant brain tumors have been proposed to be treated locally using engineered cells secreting proteins with therapeutic potential encapsulated within alginate microcapsules. Optimization of the alginate capsule bioreactors is needed before this treatment can be a reality. Recently, we have demonstrated that alginate-poly-L-lysine microcapsules made with high-G alginate and a gelled core disintegrated as cells proliferated. In this study we examined the growth and endostatin secretion of 293-EBNA (293 endo) cells encapsulated in six different alginate microcapsules made with native high-G alginate or enzymatically tailored alginate. Stability studies using an osmotic pressure test showed that alginate-poly-L-lysine-alginate microcapsules made with enzymatically tailored alginate was mechanically stronger than alginate capsules made with native high-G alginate. Growth studies showed that the proliferation of 293 endo cells was diminished in microcapsules made with enzymatically tailored alginate and gelled in a barium solution. Secretion of endostatin was detected in lower amounts from the enzymatically tailored alginate microcapsules compared with the native alginate microcapsules. The stability of the alginate microcapsules diminished as the 293 endo cells grew inside the capsules, while empty alginate microcapsules remained stable. By using microcapsules made of fluorescenamine-labeled alginate it was clearly visualized that cells perforated the alginate microcapsules as they grew, destroying the alginate network. Soluble fluorescence-labeled alginate was taken up by the 293 endo cells, while alginate was not detected in live spheroids within fluorescence-labeled alginate microcapsules. Despite that increased stability was achieved by using enzymatically tailored alginate, the cell proliferation destroyed the alginate microcapsules with time. It is therefore necessary to use cell lines that have properties more suited for alginate encapsulation before this technology can be used for therapy.

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Analysis of intrapopulation polymorphism of table carrot varieties for resistance to mycotic rot pathogens of root crops

VEGETABLE CROPS OF RUSSIA ◽

10.18619/2072-9146-2020-3-81-87 ◽

2020 ◽

pp. 81-87

Author(s):

Е. G. Kozar ◽

I. A. Engalycheva ◽

S. A. Vetrova ◽

K. S. Muhina ◽

T. S. Vjurtts ◽

...

Keyword(s):

High Efficiency ◽

Plant Protection ◽

Storage Conditions ◽

Root Crops ◽

Different Types ◽

The Stability ◽

The Individual ◽

Federal Center

Relevance. It was to study the variability of the degree of defeat of promising varieties of table carrots by diseases of various etiologies during storage for several years, to determine the level of their polymorphism based on resistance to various types of pathogens and the effectiveness of selection based on an individual immunological assessment of uterine root crops.Materials and methods. The experimental part of the work was performed in 2017-2020 at the FSBSI "Federal Scientific Vegetable Center" with carrot varietal populations of Margosha and Minor. The identification of the species composition of pathogens, the degree of damage, and the level of resistance of variety specimens were carried out in accordance with appropriate methods and determinants. For the immunological assessment of the resistance of carrot cultivars in vitro, the most virulent isolates of different types of fungi were used from the collection of the Laboratory of Immunity and Plant Protection of the Federal Center for Scientific Research.Results. It was established that in the populations of Margosha and Minor under natural storage conditions, the ratio and degree of spread of economically significant diseases differ significantly in different years. Based on an in vitro immunological assessment, a high polymorphism of the individual resistance of genotypes within both populations to the majority of micromycetes was revealed and the most resistant forms to the most dangerous types of pathogens were identified. Immunological analysis of the resulting offspring confirmed the high efficiency of group selection based on a comprehensive assessment of the stability of individual uterine root crops in vivo and in vitro.

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