Collaborative users from Creatv MicroTech, Inc. and Los Alamos National Laboratory, working with Argonne National Laboratory Center for Nanoscale Materials' (CNM) Nanofabrication & Devices Group, have demonstrated a novel fabrication process that produces high-porosity polymer nanofilters with smooth, uniform and straight pores and high aspect ratios.
The goal of nanopatterning research at the Center for Nanoscale Materials (CNM) is to provide nanofabrication support to all CNM scientific groups and to develop new nanofabrication techniques. The tool set includes state-of-the-art electron-beam nanopatterning, focused-ion-beam nanopatterning, nanoimprint, optical lithography, and advanced pattern transfer and thin-film deposition and synthesis capabilities.
Nanofilters have a wide range of applications for various size-exclusion-based separations in bioseparation and nanomedicine, such as laboratory assays, removing bacteria and viruses, drug delivery devices, implants, and sieving of nanoscale materials.
The manufacturing process uses electron-beam lithography and energetic neutral atom beam lithography and epitaxy (ENABLE) techniques. This technique allows for the fabrication of ordered hole arrays of a predetermined size and shape with high density. The method has the potential to produce a new generation of high-precision, high-porosity, bio-compatible filters with pore sizes down to 100 nanometers.
Further information: O.V. Makarova, C-M. Tang, P. Amstutz, R. Divan, A. Imre, D.C. Mancini, M. Hoffbauer, and T. Williamson, J. Vac. Sci. Technol. B, 27, 2585-2587 (2009)
AlphaRx Inc. (OTCBB: ALRX), an emerging biopharmaceutical company utilizing proprietary drug delivery technology to develop novel nano-drug delivery formulations, has named Ruby Hui as President of China Operations. In this role, Ruby will be responsible for managing AlphaRx operations in China, which include developing new business and implementing business practices that support AlphaRx's Pan-Asian initiatives.
AlphaRx Inc is targeting its drugs for the antibiotics which is third largest pharmaceutical market, totaling approximately $35 billion in worldwide sales, including $9 billion in the United States. Under development for this market are: Vancomycin (Glycopeptide), Gentamicin, Streptomycin, Tobramycin (Aminoglycoside). Planned candidates: Clarithromycin (Macrolide).
AlphaRx is also targeting the market for cancer treatment: the global cancer market is forecast to grow from $38.5bn in 2003 to $53.1bn in 2009, representing an average annual growth rate of 5.49%, Planned candidates: Taxol, Camptothecin, Cisplatin (Platinum).
Ruby has extensive experience in marketing and project management. Ruby was senior project manager at New World Development, a multi billion investment holding company with interests in health care, pharmaceuticals, property development, hotels, infrastructure, telecommunications and retailing in Hong Kong and China. Before joining New World, Ruby held various positions at Chinese Estate Group, a multi billion investment holding company based in Hong Kong that is run by Ruby's family members.
"The potential within the greater China region is enormous," said Ruby. "I am very pleased to assume this role and help build a strong executive team in China and I look forward to leading AlphaRx China towards leveraging the momentum that is building in the region and driving this company to new heights."
"I am confident that Ruby's extensive leadership and China experience as well as her high energy and proven track record will further accelerate our rapid growth in China and bring the organization to new heights," said Michael Lee, President & CEO of AlphaRx. "The timing is of great significance as the new China economic dynamic increases the demand for pharmaceuticals." Ruby is an active investor in AlphaRx and has invested over $2 million into AlphaRx and its Hong Kong subsidiary.
AlphaRx is a specialty pharmaceutical company dedicated to developing proven therapies by reformulating FDA approved and marketed drugs which through the application of its proprietary site-specific nano drug delivery technology, offers improved medical benefits and a potential for significant commercial product development.
AlphaRx has selected locations in Hong Kong and Shanghai for its corporate headquarters and a new R&D facility respectively. This initiative will spearhead a major push into Greater China.
The R&D facility will be located in The State Biotech Pharmaceutical industrial base (Shanghai) which is situated on 740 acres of land in Zhangjiang High-Tech Park, Shanghai, also known as China’s medicine valley. Established in 1996, the base is now home to 400 research-based companies including the regional headquarters of the world’s leading pharmaceutical companies, and is commonly thought of as one of the largest and most successfully drug development centers within China today.
“The Shanghai government has offered business incentives to help the decision-making process.” said Michael Lee, Chief Executive Officer and President, AlphaRx Inc. “Some of the incentives include financial assistance through various types of transactions, including grants, loan guarantees and interest subsidies which translate into substantial reduction in overall project development costs.”
There will be no impact to AlphaRx’s presence in Toronto, Canada which continues to serve as its headquarters in North America.
A*Star researchers integrated an optical coherence tomography device into a silicon optical bench, which is transparent to infrared light. Overall, the probe is just four millimeters in diameter
Medical biopsies are often carried out by removing parts of tissue for analysis, but this procedure can traumatize patients and is impossible in delicate areas such as the brain. For this reason, there is demand for new types of probe that could enter the body without causing damage and image cells in real time.
One of the most promising imaging techniques is called optical coherence tomography (OCT). C. S. Premachandran at the A*STAR Institute of Microelectronics in Singapore and co-workers have built the smallest OCT probe to date1, which could reveal the microstructure of living tissues and aid the diagnosis of cancers.
“The OCT method has both higher resolution and deeper penetration into tissue than other techniques such as ultrasound and confocal imaging,” explains Premachandran. “A conventional OCT system uses a hand-held probe 20 millimeters in diameter, which can be used for ex vivo and skin level imaging applications; but for in vivo imaging and optical biopsies, there is a clear need for miniaturized probes.”
OCT probes are simple in concept; they contain optic fibers that deliver light to the area of interest, and then collect the reflected light to build up an image. The main challenge is to make a probe that can view as much as possible with the minimum of movement.
To control the direction of their light beam and scan over a large area, Premachandran and co-workers built a ‘micromirror’ just 500 micrometers in size. Their mirror is supported by four springs that can be thermally activated to move the mirror around, rotating it up to 16°. The light is focused onto the mirror by a ‘graded-index’ lens, providing a large working distance despite the device's small size.
“Our probe is slightly smaller than other probes reported in the literature,” says Premachandran. “We are now working to reduce the diameter further to three millimeters.” He and his co-workers also hope to develop 360° scanning so that the whole area surrounding the probe can be scanned and imaged.
“Currently we have only tested our probe by imaging onion tissue, so our next move is to do imaging on animal tissue and cancers. Finally we will try it in a live animal model and develop oral cancer applications for humans.”
Premachandran, C.S., Khairyanto, A., Sheng, K.C.W., Singh, J., Teo, J., Yingshun, X., Nanguang, C., Sheppard, C. & Olivo, M. Design, fabrication and assembly of an optical biosensor probe package for OCT (Optical Coherence Tomography) application. IEEE Transactions on Advanced Packaging32, 417–422 (2009). | article
In U. S. Patent Application 20090306198, Dr. Robert Nicolosi (Nashua, NH) and Thomas Shea (Billerica, MA) disclose a uniform microfluidized nanoemulsion containing a synergistic combination of two antioxidants and a cell membrane stabilizer phospholipid (i.e., an anti-oxidant synergy formulation; ASF). The microfluidized nanoemulsion improves the combination's cell membrane permeability by at least four-fold over conventional nanoemulsion compositions, which significantly increases the intracellular concentration of typically cell-impermeant antioxidants (i.e., for example, tocopherol) and/or systemic bioavailability. As a nanoemulsion, synergistic combination has greater anticancer efficacy than the same combination applied as a free solution
Solid tumors arise in organs that contain stem cell populations. The tumors in these organs consist of heterogeneous populations of cancer cells that differ markedly in their ability to proliferate and form new tumors. In both breast cancers and central nervous system tumors, cancer cells differ in their ability to form tumors. While the majority of the cancer cells have a limited ability to divide, a population of cancer stem cells has an exclusive ability to extensively proliferate and form new tumors. Growing evidence suggests that pathways regulating a self-renewal of normal stem cells may be deregulated in cancer stem cells thereby resulting in a continuous expansion of self-renewing cancer cells and tumor formation. This suggests that agents that target the defective self-renewal pathways in cancer cells might lead to improved outcomes in the treatment of these diseases. Currently, challenges regarding drug delivery to solid tumors are impeding progress in this field.
Neuroblastoma, the most common of all cancers found in children, may arise from a biochemical block of cellular differentiation and a resultant continuation of a proliferative state. Neuroblastoma often spontaneously reverts by undergoing partial differentiation and ultimate degeneration. The nanoemulsion may be a useful therapeutic approach for clinical neuroblastoma comprising strategies to force neuroblastoma to differentiate. The differentiation strategy comprises a reduction in intracellular reactive oxygen species.
A long-term research alliance agreement between CSIRO and Australian biotechnology company Circadian Technologies will aid in developing promising new potential treatments for cancer. The agreement was announced on December 7th by CSIRO Group Executive, Dr Steve Morton.
Under the agreement, CSIRO will work with Circadian on a class of proteins developed by the company called Vascular Endothelial Growth Factors (VEGFs) that play a critical role in regulating tumor blood supply.
Circadian, which owns extensive intellectual property related to the VEGF technology is developing antibodies to block these proteins to inhibit the growth and spread of cancerous cells or tumors.
Circadian will provide funding and access to its technology and lead drug candidates (molecules), while CSIRO will provide access to its world-class biological production infrastructure, process development capability and internal research expertise.
The announcement was made at the opening of a new Recombinant Protein Production Facility in Melbourne that is housed in Monash University and CSIRO. Dr Steve Morton, CSIRO Group Executive said "CSIRO is very pleased to be working with Circadian to advance its product development pipeline," Dr Morton said. "This alliance highlights that there is already industry uptake of our new Protein Production Facility and research capability. CSIRO is all about partnering with and delivering to Australian industry and our new Facility will be a key enabler for the biotech industry."
The alliance is part of the CSIRO's program to assist and facilitate development of new technologies with Australian biotech companies.
Circadian's CEO, Robert Klupacs, CEO of Circadian said the collaboration will greatly assist the company to advance its research. "Circadian has a strong position in this area of potential therapeutics for cancer and we applaud the vision of the CSIRO to work closely with Australian companies such as ours, encouraging us to continue to develop important new treatments and innovations which may one day have the potential to impact on many lives globally," Mr Klupacs said.
Attending the announcement was Senator the Hon Kim Carr Federal Minister for Innovation, Industry, Science and Research and Gavin Jennings MLC Victorian Minister for Innovation. The Facility was funded by both the Federal and Victorian governments, and will play a significant role in enabling the Australian biotechnology industry to accelerate product development.
An EU-funded research team has developed a biosensor that can identify immune system cells that actively suppress tumour growth. This biosensor can help patients use their immune systems to fight cancer. The COCHISE ('Cell-on-chip biosensor for detection of cell-to-cell interactions') project received $2.58 million (EUR 1.74 million) under the 'Information Society Technologies' (IST) Thematic area of the EU's Sixth Framework Programme (FP6).
Existing cancer treatments used specifically in immuno-oncology use medications that strengthen the immune system or colony-stimulating factors (CSFs stimulate the production of blood cells). The problem, however, is that these treatments tend to trigger a reaction in patients. Experts have speculated that selecting, amplifying and re-injecting 'active cells' into the body would be a more effective approach, making for a win-win situation with no risk of rejection or side effects. The only glitch, however, is that no simple, cheap and reliable method to identify the active cells is on the market.
COCHISE partners believe their biosensor will change all that thanks to its characteristic of being able to identify interactions between single cells. According to the team, the biosensor detects signals from biological activity.
The researchers explained that in the initial phase, the biosensor uses a mix of microfluidics and electronics to isolate immune system cells and cancer cells in a microwell. Active cells are then identified in phase two. The central factor in this analysis is electronics. Dielectrophoresis, a process used to manipulate particles, forces the cells together and doctors can observe interactions between them. The active cells are then separated from the rest, they said.
'The procedure we identified for measuring cell activity is at the core of the technology,' explained Dr Massimo Bocchi, chief technology officer (CTO) at Italy's MindSeeds Laboratory, a COCHISE partner.
'Basically, we demonstrated, using reference cell lines, that the expected interactions between cells of the immune system and tumour cells can be reproduced in microstructures, such as the microwell, at the single-cell level.
'When an event of interest is measured, [say] a cell of the immune system kills a target tumour cell, the cell of interest can be retrieved from the platform, [and] transferred to a standard plate and culture,' he added. 'This complete workflow allows doctors to study the behaviour of cells because we are able to isolate them on the basis of their functional activity. This is a key innovative concept in this field.'
All in all, the COCHISE team succeeded in obtaining their objective, and also developed a new fabrication process and found appropriate biocompatible materials.
Another positive element of the biosensor is that it could potentially be used to produce targeted cancer vaccines, almost like a 'tuning of the patient's immune system', he noted.
The biosensor has already attracted the attention of the medical sector and industry. 'Several research institutes and hospitals [showed interest] in this platform for studying the mechanisms of the immune system with a single-cell resolution, and to see the potential applicability to gene-therapy applications,' Dr Bocchi said.
The COCHISE consortium consists of eight partners from Belgium, Germany, France, Italy and the Netherlands.
NanoBio Corporation announced on December 2nd positive results from studies in mice in which immune responses were evaluated following administration of 5µg doses of recombinant H5N1 pandemic flu antigen combined with the company’s novel nanoemulsion vaccine. These studies are unique because the adjuvant was administered for the first time by subcutaneous (SC) and intramuscular (IM) injections. The mice that received either SC or IM H5 antigen combined with nanoemulsion had maximal immune responses at least a 1000 fold higher than control animals that received the same antigen IM without the nanoemulsion adjuvant. SC and IM administered NanoBio adjuvanted vaccines should share many of the advantages, including antigen-sparing properties, previously demonstrated in studies where the adjuvant was administered intranasally.
“It is encouraging that these strong immune responses were achieved without evidence of significant irritation or inflammation, which could differentiate these IM vaccines from currently approved IM adjuvants,” commented James R. Baker, Jr., M.D., founder and CEO of NanoBio Corporation. “These new data further demonstrate the broad safety and potential universal applicability of NanoBio’s vaccine adjuvant platform for immunization in a method most appropriate for the particular disease.”
The underlying technology is NanoBio’s NanoStat™ platform, which employs a nanoemulsion that is created through a proprietary manufacturing process. The nanoemulsion has previously proven to be uniquely capable of permeating the nasal mucosa, where it can load vaccine antigen into immune-presenting cells. Earlier this year, the U.S. Food and Drug Administration (FDA) approved the company’s Investigational New Drug (IND) application for the Phase 1 clinical study of NB-1008, a seasonal influenza vaccine administered via a nasal dropper. The Phase 1 study is ongoing.
NanoBio’s nanoemulsion-based, intranasal vaccines have elicited robust immune responses in animals vaccinated against seasonal and pandemic influenza, hepatitis B, RSV, HIV, pneumococcal, anthrax, smallpox and other diseases. The company’s NanoStat™ adjuvant platform technology has demonstrated numerous potential advantages over traditional vaccines, including: the ability to generate robust mucosal, systemic and cellular immunity; antigen-sparing qualities; cross-protection against non-vaccinated strains; ability to adjuvant multiple antigen types without inducing inflammation; thermally stabilizing the vaccine; and removing the need for needles.
NanoBio® Corporation is a privately held biopharmaceutical company focused on developing and commercializing dermatological products, anti-infective treatments and intranasal vaccines derived from its patented NanoStat™ technology platform. The company’s lead dermatology and anti-infective product candidates include treatments for herpes labialis (cold sores), onychomycosis (nail fungus), tinea capitis, acne, molluscum contagiosum, and cystic fibrosis. The company’s headquarters and laboratory facilities are located in Ann Arbor, Michigan. NanoBio is a spin-off from the University of Michigan and holds the exclusive global license to the nanoemulsion platform technology.
