Case Study: Expansile Particles for Drug Delivery
Case Study: Nano-Engineering of Smart Drug Delivery Particles at Boston University
Accuracy of measurement of nanoparticles is a fundamental requirement for research involving smart particles for drug delivery.
Professor Mark Grinstaff and members of his group in the Departments of Biomedical Engineering and Chemistry at Boston University, have been researching the use of ‘expansile’ nanoparticles and hydrophilic triggers for targeted drug delivery. Specifically, new nanoparticle compositions are being developed that are pH responsive, which swell and release their contents once inside cancer cells.
Nanoparticles have been prepared using mini-emulsion polymerization chemistry, combining high-energy emulsification and free radical photopolymerization of an acrylate monomer. The effect of varying pH solutions on the size of these smart particles is then measured, by comparing particle-by-particle size and concentration details of the mixture at each pH level. Accurate measurement of particles both before and after the pH change is a crucial aspect in assessing the physical properties, reaction kinetics and drug efficacy.
Izon’s qNano is being used by the research group to measure various parameters (size, surface charge and concentration) of the synthesized nanoparticles before, during and after each phase change at varying pH conditions. Earlier measurements obtained using DLS did not provide the degree of accuracy and reliability required, and Izon’s nanopore technology is now being used to provide particle-by-particle measurement for a much higher degree of detail and precision.
Investigation into the flexibility and deformability of the particles is a further aspect enabled by Izon’s qNano by gating of the smart particles with the tunable nanopore.
Further Reading: AP Griset, J Walpole, R Liu, A Gaffey, YL Colson, and MW. Grinstaff. (2009) “Expansile Nanoparticles: Synthesis, Characterization, and In vivo Efficacy of an Acid-Responsive Polymeric Drug Delivery System.” Journal of the American Chemical Society, 131, 2469-2471
Case Study: Drug Delivery Research
Case Study: Characterisation of Hollow Polymer Capsules for Drug Delivery Research using qNano
Professor Frank Caruso and his team at the Melbourne Materials Institute at the University of Melbourne, are investigating Layer-by-Layer (LbL) assembled nanoengineered capsules that have applications as drug delivery vehicles. Izon’s technology is being used by members of the research group to quantify the capsules as well as to investigate the flexibility of the hollow structures. The capsules are made by adsorbing the layers onto a silica template which is later removed.
Their research requires accurate quantification of the capsules to ensure consistent dosing for in vitro and in vivo experiments. Sarah Dodds, a post-graduate researcher in Professor Caruso’s team, has been using the qNano to accurately measure the concentration of the nano-engineered capsules, which are difficult to quantify any other way due to their small size.
In addition to quantification, Sarah and Dr. Angus Johnston are using the qNano to probe the flexibility of the capsules. This characteristic is of interest as it has implications for the ability of the delivery vehicles to reach their target site in the body. An understanding of deformability is needed to explain the in vivo behaviour of capsules. The tunable nanopore in the qNano allows comparison of LbL systems with and without the silica template used in synthesis.
Further Reading: Modular assembly of layer-by-layer capsules with tailored degradation profiles. Ochs CJ. Such GK. Caruso F.Langmuir. 27(4):1275-80, 2011 Feb 15.
Case Study: Diagnostics Research
Case Study: Detailed Studies of Particle Functionalisation Kinetics aid Diagnotics Research.
Researchers at the Biomedical Diagnostics Institute at the National Centre for Sensor Research at Dublin City University have chosen Izon's qNano system to advance their research into functionalised nanoparticles for diagnostic applications. One of the projects is to develop an assay using antibody functionalised nanoparticles to accurately detect and measure antigens of interest. Detailed engineering of the system requires optimisation of many factors including particle size and charge, antibody-particle ratio, checking the rate of the antibody-antigen reactions, and using the kinetics of agglutionation to determine antigen quantity. Accurately quantifying the number of particles and biomolecules being bound is an essential step in the engineering process.
The qNano's single-particle detection approach, and unique resolution capability in both particle size and surface charge, provide valuable insight into the sensitisation process of nanoparticles for bio-diagnostic applications.
Key researcher on the project, Dr. Vladimir Gubala, said he is excited about the initial results and sees the qNano being applied across many research projects within the group."Izon has provided us with so much support on this work and really made it easy for us to push the limits and try new ideas" he said. "We're doing research that is really taking the platform to a new place and showing what it can do, and we're excited to be the ones to do it."
Further Reading: A comparison of mono and multivalent linkers and their effect on the colloidal stability of nanoparticle and immunoassays performance. Gubala V. Le Guevel X. Nooney R. Williams DE. MacCraith B. Talanta. 81(4-5):1833-9, 2010 Jun 15.
Case Study: Exosome Analysis
Case Study: Improving Microparticle Detection at University of Amsterdam
Microparticles and exosomes are microvesicles present in body fluids, derived from the plasma membrane of cells and platelets. They play important roles in normal processes (coagulation, inflammation, cellular homeostasis and survival, intercellular signaling, and transport of waste materials) as well as a number of disease states.
The size, concentration, and biochemical composition of these vesicles contain clinically relevant information – that is expected to lead to improved diagnosis and treatment of disease. However, because of the small size of most vesicles (30 nm – 1 µm), they are below the detection range of many currently used techniques.
Edwin van der Pol works with a team of researchers headed by Prof. Ton van Leeuwen and Dr. Rienk Nieuwland, at the Departments of Biomedical Engineering & Physics and the Laboratory for Experimental Clinical Chemistry, Academic Medical Center (AMC), University of Amsterdam.
The center is unique in that it evolved from a fusion of the Departments of Medical Physics and the Laser Center in 2008. With its expertise in haemodynamics, cardiovascular biophysics, and applications of biomedical photonics and quantitative medical imaging, the center regularly provides support for physicians and clinical researchers.
In preliminary experiments AMC researchers have shown that the qNano is capable of measuring the size and concentration of individual vesicles directly in suspension.
The group intend to combine the qNano with complimentary detection methods, so that parallel information on the biochemical composition of macromolecules inside living cells can be determined on a vesicle-by-vesicle basis.“The simultaneous detection of the size, concentration, and biochemical composition from single vesicles would be a major step forward”, says van der Pol. “We expect that the improved detection of vesicles will provide an entirely new level of clinical information, which is likely to become an integral part of routine health care.”
Further Reading (requires Journal Access): van der Pol E, Hoekstra AG, Sturk A, Otto C, van Leeuwen TG, Nieuwland R. Optical and non-optical methods for detection and characterization of microparticles and exosomes. J Thromb Haemost 2010; 8: 2596–607.
Case Study: Viral Vaccines
Case Study: Virus characterisation at the Jenner Institute
The Jenner Institute, a world leading non-profit organisation for vaccine development located in Oxford, UK, has been applying the SIOS measurement approach to assess their viral sample preparations. The Institute is developing promising new vaccine candidates against major global infectious diseases and currently has new vaccines against malaria, tuberculosis and HIV in field trials in the developing world.
Dr. Ali Turner, Vector Core Facility Deputy Manager, and Jake Matthews, a post-graduate researcher at the Institute, are using SIOS technology to further their research into vaccine vectors. Key parameters of interest include accurate measurement of viral titre as well as assessment of levels of aggregation within the virus samples. An understanding of the level of aggregation is particularly important to ensure the quality of the vaccine produced from the virus. Work is focusing on two viruses, Adenovirus and Modified Vaccinia Ankara (MVA) virus, both used extensively as vectors or delivery vehicles in both vaccinology and gene therapy.
Researchers at the institute contributed to a paper on particle sizing analysis using the SIOS approach demonstrating the resolution capability of the qViro instrument for virus samples, clearly distinguishing single adenovirus particles from two particle aggregates.
Further Reading: "Quantitative Sizing of Nano/Microparticles with a Tunable Elastomeric Pore Sensor" Robert Vogel, Geoff Willmott, Darby Kozak, G. Seth Roberts, Will Anderson, Linda Groenewegen, Ben Glossop, Anne Barnett, Ali Turner and Matt Trau.Journal of Analytical Chemistry 83 (9), pp 3499–3506 (2011).
Case Study: Nanoeducation
The National Science Foundation projects a global demand of two million nanotechnologists and six million support personnel by 2015. At present there are only 100,000 nanotech employees in the global workforce, which provides a challenging workforce gap to nano-based companies moving from R&D to commercialization.
It is not surprising that nanotechnology courses are becoming an important part of the curriculum for a number of forward-thinking educators. Both Forsyth Tech & Nanoprofessor have recently purchased the qNano as a tool for teaching students about nanotechnology. The ability to detect, count, and characterize nanoparticles - are key features making the instruments useful tools to learn about the physical properties of nanoparticles.
Dr. Kevin Conley, Program Coordinator of Nanotechnology Education says,
“We prepare graduates for multidisciplinary careers. We train them to be compatible with biologists, chemists, physicists, and engineers. Our graduates are then able to help incorporate nanotechnologies into startup and established companies in the region. We also teach economics alongside the sciences to help promote growth of the nanotechnology sector in the US.”
According to Dr. Conley, single-particle event counting will be the way forward for the nanotechnology industry. “The industry-standard particle-sizing method is DLS (Dynamic Light Scattering). This method reports averages over thousands of particle events. The qNano reports precise data for single events. In the long run, the simpler, more elegant method always wins.”
Forsyth Tech will further build the skills of students through collaborations and exchanges with other education institutes such as the University of Victoria in Wellington, New Zealand. Forsyth Tech is the first customer in nano-education and the 100th customer using the instrument. A special All-Blacks edition 100th Instrument has been presented to commemorate the occasion (below).
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NanoProfessor®, a division of NanoInk, Inc.® aims to expand hands-on nanotechnology education from the cleanrooms of research-based universities to undergraduate classrooms, at the community college, technical institute, and undergraduate university level.
“We are extremely proud to have Izon as a strategic educational partner and excited to add Izon’s qNano characterization instrument to the NanoProfessor Program”
"With the addition of the qNano instrument, the NanoProfessor Program provides students significant hands-on experience and skills in nanoscale fabrication of metallic nanoparticles and biologic agents, nanoscale imaging, and nanoscale characterization. This unsurpassed level of hands-on experience translates to a higher level of student preparedness for exciting jobs and careers in the blossoming nanotechnology industry.”
Dean Hart, Chief Commercial Officer of NanoInk.