Everything about Microspheres
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  • Suspension of Hydrophobic Particles in Aqueous Solution – Density Gradients

    Fluid Flow Visualization using Microspheres, Spherical Particles

    Fluorescent polyethylene microspheres for flow visualization in aqueous systems. Suspension of beads in aqueous solutions.

    Background Information

    Many materials are hydrophobic (water-fearing) in nature. Due to their non-polar chemical structure, hydrophobic particles want to minimize contact with polar (water) molecules and, as a result, tend to aggregate on the surface of the water and resist going into suspension. This presents a challenge to scientists and engineers who would like to be able to work with hydrophobic particles suspended in aqueous solution.

    Examples of the applications are using fluorescent polyethylene microspheres for flow visualization in aqueous systems, creating density gradients, filtration and contamination control studies.

    Fortunately, there is a simple way to overcome the hydrophobic effect. It is called a surfactant, a detergent, or simply “soap.” Surfactant is a magical molecule that has both hydrophobic and hydrophilic properties, which coats the particles and helps them mix into water. The same mechanism applies when we use soap to wash greasy dishes or stained clothes.

    Selection of the surfactant depends purely on your process and product requirements. Dishwashing liquid works great, so does Simple Green. For scientists working on biological applications we recommend the use of Tween surfactants. Tween is the commercial name for Polysorbate non-ionic surfactants, which are stable, nontoxic, and often used in pharmacological, cosmetic, and food applications. Non-ionic detergents are considered to be “mild” detergents because they are less likely than ionic detergents to denature proteins. By not separating protein-protein bonds, non-ionic detergents allow the protein to retain its native structure and functionality.

    Tween 20 and Tween 80 are frequently used. Both surfactants are yellowish, water-soluble viscous liquids. Primary difference between the two is viscosity. Tween 20 has lower viscosity and is easier to work with.

    Suspension Process

    There are many ways to suspend the particles (e.g. put a few drops of dish detergent into water and shake with the particles).

    The process below is specific for using the minimum amount of Tween for biologically sensitive applications.

    Safety:

    • Gloves and eye protection are to be worn at all times during solution preparation and use.
    • Care should be taken when handling hot objects/liquids and immersion blender.
    • Centrifuge should be properly balanced and allowed to come to a full stop before opening.

    Recommendations:

    • We recommend using distilled water to minimize impurities.
    • We recommend boiling the water to sterilize and to make it easier to disperse a small amount of surfactant uniformly. This also increases shelf-life of prepared solutions and suspensions.
    • We use an immersion blender to disperse the surfactant in water quickly and effectively.

    Process:

    Preparing Tween Solution:
    • Fill a heatproof container with distilled water.
    • Ensure the water level is high enough to cover the immersion blender.
    • Heat water to boiling and leave boiling for 5 minutes.
    • Weigh out 0.1g of Tween per 100ml of water used (creating 0.1% solution).
    • Slowly add Tween to boiled water while mixing with immersion mixer (~30 seconds).
    • Some bubbles will form during mixing.
    • Bubbles will dissipate on cooling and solution will appear clear.
    Suspending particles in Tween solution.
    • Place the desired amount of particles into a container.
    • Dispense prepared Tween solution on top of particles.
    • We recommend at least five times greater volume of solution to the volume of particles.
    • Cover tightly and place containers into a centrifuge.
    • Centrifuge on highest setting for at least 5 minutes.
    • If some particles are still floating on the surface of water, more centrifuging may be necessary.
    • A small quantity of particles may accumulate on the top surface and not enter solution despite additional centrifugation. Typically, these particles will go into suspension over time (hours).
    Other Considerations
    • A greater length of centrifuging or larger volume of Tween solution may be necessary to suspend certain materials and particle sizes.
    • As a 0.1% Tween solution is sufficient for most applications, concentration levels could be raised to support particles that are more resistant to entering solution.
    • Once the particles are suspended, solution can may be diluted further to increase the volume.
    • Particles can be recycled and reused as necessary. The suspension might need to be repeated.
    • If no centrifuge is available, it is possible to shake the container by hand (up and down, upside down) to achieve the same result.

    Here is an example of Cospheric fluorescent beads 150 to 180micron in diameter being dispersed in a pilot bioreactor.

    About Cospheric

    Our extensive product line consists of more than two thousand unique spherical microparticle and nanoparticle products, all developed based on customer demand. We work with each individual customer to find a creative solution for their unique needs ­– tight particle size ranges, wide selection of colors, densities, properties and formulations. We are the sole global supplier for the majority of our products. We developed a disruptive technology which is redefining the microsphere market and creating a new category of precision spherical particles. Our research department is always excited to tackle new challenging projects. Explore at www.Cospheric.com.

    Other Information

    The information contained in this document is correct to the best of our knowledge at the date of publication. It should not be viewed as all inclusive, but as a guide only. It does not represent any guarantee of the properties of the product. Cospheric LLC shall not be held liable for any damage resulting from handling of or from contact with the above product. For these reasons, it is important that product users carry out their own tests to satisfy themselves as to the suitability of the safety precautions for their own intended applications.

  • Microspheres Used as a Drug Delivery System

    There has been numerous studies done and articles published in scientific publications about the advantages of microspheres as a drug delivery system vs conventional approach to drug delivery.  Design, Development and Future Application of Microspheres by Divya Rawat , U.K> Singh and Faizi Muzaffar,  Kharvel Subharti College of Pharmacy, published in PharmaTutor discusses the types of microspheres that posses the properties needed for various drug delivery systems, their advantages and limitations.  The micropsheres best suitable to be used in biomedical applications, research and lab experiments are polystyrene.  According to the article: “Polystyrene microspheres are typically used in biomedical applications due to their ability to facilitate procedures such as cell sorting and immune precipitation. Proteins and ligands adsorb onto polystyrene readily and permanently, which makes polystyrene microspheres suitable for medical research and biological laboratory experiments. Polyethylene microspheres are commonly used as permanent or temporary filler. Lower melting temperature enables polyethylene microspheres to create porous structures in ceramics and other materials. High sphericity of polyethylene microspheres, as well as availability of colored and fluorescent microspheres, makes them highly desirable for flow visualization and fluid flow analysis, microscopy techniques, health sciences, process troubleshooting and numerous research applications.”

    Another research paper that discusses advantages and disadvantages of microspheres use for drug delivery, as well as techniques to prepare microsheres and principle behind drug delivery system is Microspheres as Drug Carriers for Controlled Drug Delivery: a Review by Nisha Sharma, Neha Purwar and Prakash Chandra Gupta, University Institute of Pharmacy, C.S.J.M. University, Kanpur, India published in International Journal of Pharmaceutical Sciences and Research.  Polymer microspheres were used for the experiment. The authors conclude that “microspheres are better choice of drug delivery system than many other types of drug delivery system. In future by combining various other strategies, microspheres will find the central and significant place in novel drug delivery, particularly in diseased cell sorting, diagnostics, gene & genetic materials, safe, targeted, specific and effective in-vitro delivery and supplements as miniature version of diseased organ and tissues in the body.”

  • Negatively-charged Yellow Microparticles – Back in Stock

    Highly Negative Charged Microspheres - Polyethylene, Selection of Sizes 5 to 500um

    Highly Negative Charged Microspheres - Polyethylene, Selection of Sizes 5 to 500um, 1.0g/cc

    Cospheric’s neutrally-buoyant highly charged yellow microspheres have a strong negative charge and are used by scientists in medical technology, biotechnology, applied physics and research. Precise particles with known density of 1.0g/cc that behave in a known way are useful as a model particles in simulation experiments.  Particles in a range of diameters from 5micron to 500micron(0.5mm) are currently back in stock.

    Bright yellow polymer microparticles of high sphericity are spherical polyethylene beads that are specifically designed with density ~1.0g/cc for suspension in fresh water,  serving as seed or tracer particles and enabling flow visualization and Particle Image Velocimetry PIV analysis of fluid flow in a device. It is often advantageous to color code the particles by size to better understand which part of the process the spheres of the specific size were able to pass through, or where the contamination in the process is coming from. Microspheres are supplied in dry powder form and are color stable in solution. No solvents are used in the manufacturing process. Polyethylene is inert to most solvents.

    Cospheric also offers unique capability to manufacture Bichromal janus microspheres and microparticles with partial coatings and potentially dual functionality. Currently half-shell or hemispherical coatings can be applied to any sphere (glass, polymer, ceramic) in sizes 45micron in diameter and higher. Coatings can be customized for any color and coverage of between 20% to 60% of the sphere. Each coating is custom formulated for color, charge, magnetic, electric, and surface properties, and solvent resistance per customers’ needs. Hemispherical coatings of less than 1 micron with tolerances as low as 0.25 micron have been routinely demonstrated.  Color combinations are truly unlimited. White, black, silver, blue, green, red, yellow, brown, purple as well as transparent microspheres have been made. Sphericity of greater than 90% and custom particle size ranges are offered.

    It would be interesting to combine these highly charged yellow microspheres with a partial paramagnetic black coating and investigate the behavior of these spheres in electromagnetic field.

  • BioCompatability of Metal Coated Spheres

    For those scientists who are looking to use silver coated materials such as silver coated microspheres in biomedical applications, it is important to understand whether they are bio-compatable.  A selection of abstracts and article references related to the biocompatability of silver follow:

    The Biocompatibility of Silver2

    The experiments reported have referred to some of the characteristics of the biocompatibility of Ag. Silver has been shown to display interactions with albumin, as an example of a plasma protein, quite different from those of most metals. Such studies shed further light on the complex issue of protein adsorption on biomaterials. It has also been demonstrated that Ag at concentrations < 1 ppm exerts a considerable influence on the activity of lactate dehydrogenase, this effect being reversed in the presence of albumin. A significant but transient increase in blood levels of Ag following intramuscular implantation of the metal has been observed. This is not reflected in any raised urine level. It is proposed that the richly vascular tissue immediately surrounding the implant in the acute phase of the response gives rise to the transient increase, but a subsequent decrease in vascularity reduces this possibility. It appears that Ag released from implants following this initial period substantially remains in the local area.2

    Lack of toxicologocial side-effects in silver-coated megaprostheses in humans1

    Deep infection of megaprostheses remains a serious complication in orthopedic tumor surgery. Furthermore, reinfection gets a raising problem in revision surgery of patients suffering from infections associated with primary endoprosthetic replacement of the knee and hip joint. These patients will need many revision surgeries and in some cases even an amputation is inevitable. Silver-coated medical devices proved their effectiveness on reducing infections, but toxic side-effects concerning some silver applications have been described as well. Our study reports about a silver-coated megaprosthesis for the first time and can exclude side-effects of silver-coated orthopedic implants in humans. The silver-levels in the blood did not exceed 56.4 parts per billion (ppb) and can be considered as non-toxic. Additionally we could exclude significant changes in liver and kidney functions measured by laboratory values. Histopathologic examination of the periprosthetic environment in two patients showed no signs of foreign body granulomas or chronic inflammation, despite distant effective silver concentrations up to 1626 ppb directly related to the prosthetic surface. In conclusion the silver-coated megaprosthesis allowed a release of silver without showing any local or systemic side-effects.1

    Specific Article References for the biocompatability of silver are below: See the References

  • Microspheres for Medical Devices – MDDI Magazine – January 2011

    The Microsphere of Influence

    Published: January 2011, MDDI

    Published on MDDI Magazine
    By: Yelena Lipovetskaya

    Find more content on: Feature, Nano and Microtechnology, Technology, Testing and Inspection

    Microspheres come in many different grades and sizes, and are usually solid particles that are composed of polymers, glass, and ceramics. All images courtesy of COSPHERIC LLC

    Microspheres are round microparticles that typically range from 1 to 1000 μm in diameter. In the pharmaceutical and cosmetics industry, microspheres are well known for their ability to deliver active materials. This process usually involves the microencapsulation of a drug or an active cosmetic ingredient to protect it from the deteriorating effects of the environment or for optimal release and performance in the final product. Active ingredients are released by dissolution of the capsule walls, mechanical rupture (rubbing, pressure, or impact), melting, or digestion processes. Solid microspheres are widely used as fillers and spacers in a variety of industries.

    Microspheres used to manufacture and test medical devices are typically solid particles that are made from robust and stable raw materials such as polymers, glass, and in some cases, ceramics. Different types and grades of microspheres are available and selected based on specific application requirements.

    They are often used as tracers and challenge particles in medical devices. In these situations, it is beneficial to use larger microspheres with sphere diameters greater than 50 μm that are vividly colored (red, blue, black, yellow, or green), since they provide contrast with the background material and visibility to the naked eye in daylight. Colored microspheres are typically used in the testing of filtration media and systems, vial and container cleaning evaluations, flow tracing and fluid mechanics, centrifugation and sedimentation processes, pharmaceutical manufacturing, and contamination control.

    Fluorescent microspheres are recommended for applications that require the use of particles that emit distinctive colors when illuminated by UV light and offer additional sensitivity for observation through the use of microscopes, lasers, and other analytical methods. Examples include microcirculation and biological research, imaging, and flow cytometry. Fluorescent microspheres can be excited and detected by a wide range of methods and are useful as experimental particles for acoustical and optical analytical systems.

    Continue reading “Microspheres for Medical Devices – MDDI Magazine – January 2011” »