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High Throughput Therapeutic Protein Purification
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R&D News.......................... 1 Appointments..................... 6 Pharma Notes..................... 7 New Products................... 14 Calendar........................... 17 Career Spotlight............... 18
Dr. Andras Nagy
Discovery opens avenue for research into new veterinary and human treatments for a range of degenerative conditions
In a world first, pluripotent stem cells have been generated from horses by a team of researchers led by Dr. Andras Nagy at the Sam-
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uel Lunenfeld Research Institute of Mount Sinai Hospital in Toronto and Dr. Lawrence Smith at the Université de Montréal’s Faculty of
Veterinary Science. The findings will help enable new stem-cell based regenerative therapies in veterinary medicine, and because horses’ muscle and tendon systems are similar to our own, aid the development of preclinical models leading to human applications. The study was published in the leading journal Stem Cell Reviews and Reports. These induced pluripotent stem (iPS) cells can develop into most other cell types and are a source of great hope for use in regenerative medicine and the development of new drugs to prevent and treat various illnesses. One aspect of regenerative medicine is the process of creating living, functional tissues to repair or replace tissue or organ function lost due to damage or disease. “To date, iPS cells have been established from several species, but our study is the first to report the derivation of these changeable cells from horses,” Dr. Smith explained. The research represents a breakthrough for both human and animal health alike. “Equine iPS cells bring new therapeutic potential to the veterinary field, and open up the opportunity to validate stem-cell based therapies before clinical studies in humans,” Dr. Nagy said. “As well, stem-cell based studies using the horse as a model more closely replicate human illnesses, when compared with studies in mice.” After two months of reprogramming equine somatic cells, the resulting iPS cell lines expressed hallmark markers of pluripotency, contained a correct set of horse chromosomes, and were able to form a full spectrum of cell types and tissues fulfilling the criteria of pluripotency. The term pluripotency
refers to the ability of a stem cell to become any of the vast number of different cell types found in the body. “This means that the cell lines passed all the tests available to us for determining if they truly are what we think they are: pluripotent and a good source for future regenerative applications,” said Kristina Nagy, research associate in the Nagy laboratory and lead author of the study. “The horse serves as an excellent model in which to test cell therapy, both clinically and experimentally, for a range of human degenerative diseases,” said Dr. Sheila Laverty, an equine surgeon and professor, Comparative Orthopaedic Research Laboratory, Faculty of Veterinary Medicine at the University of Montréal. “Tendon, bone and cartilage often heal sub-optimally in both and result in a loss of function and long-term disability. iPS cell therapy offers tremendous hope for enhancing repair and regeneration of these tissues in both horses and humans.” Further research is underway to develop clinical treatments. Dr. Andras Nagy is a senior investigator at the Lunenfeld and a professor in the Department of Molecular Genetics at the University of Toronto, the Canada Research Chair in Stem Cells and Regeneration and a McEwen investigator. He received support from the Canadian Stem Cell Network of Canada for this research. Dr. Smith is the Canadian Research Chair in Animal Cloning and Stem Cells and received support from the Canadian Arthritis Network. His lab plays a key role in the University of Montréal’s Animal Reproduction Research Centre.
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March 2011 Laboratory Focus www.bioscienceworld.ca
news Vineland to Host Leading Edge Plant Genomics Conferenceterventions for neglected global diseases Vineland Research and Innovation Centre will welcome scientists and horticulture industry representatives from around the globe to an upcomingDec.2010Nunc.BD.LabFocus.pdf three day conference
August 22 to 25, in Niagara Falls, ON. “This event will bring together Canadian researchers and internationally-renowned sci12/22/10 AM advances in entists 10:09:38 to explore
genomics research within the plant sciences,” said Dr. Daryl Somers, Vineland’s research director Applied Genomics. “Leading edge research is valued at Vineland, to maximize
our impact on industry we need to bring the best minds in genomics together.” Early sponsorship support Continued on page 3
staff writer Shawn Lawrence CONTRIBUTING WRITERS David Knorr Marc Beban Mukesh Mayani Zachary Van Den Heuvel NATIONAL ACCOUNT MANAGER Patricia Bush
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March 2011
news Continued from page 2
CDRD Partners with NGDI-UBC to develop new interventions for neglected global diseases
has been impressive. Contributions from Genome Prairie, Canola Council, Pioneer Hi-Bred, DNA Landmarks, BioRad, and Ontario Ministry of Agriculture, Food and Rural Affairs are setting strong examples by industry and government on the value of this event. “For over a decade this workshop has showcased the investment of genomicsbased approaches to plant science that has demonstrated true value to many industrial partners. We welcome the opportunity to be a part of this very important event,” said Reno Pontarollo, CSO Genome Prairie. To send a message of encouragement to young and upcoming scientists, the conference is also including the CPWG graduate student poster competition. Local and international students
will be awarded up to five grants of $500 and will receive special recognition following a judge’s panel evaluation. “This conference is more than just a session for scientists, it is designed to strengthen the connections between good research and industry application. Communicating outcomes to our industry partners will be an important part of the conference,” said Dr. Jim Brandle, CEO Vineland. Outcomes of the workshop will include strategic relationships with the scientific community, expanded partnerships with strengthened technology transfer between researchers. For further information go to www.cpgw2011.com or contact Vineland Research and Innovation Centre.
The Centre for Drug Research and Development (CDRD) and the Neglected Global Diseases Initiative at the University of British Columbia (NGDI-UBC) announce that they will collaborate on developing interventions for neglected global diseases and ensuring their delivery to those in need. “We hope to leverage CDRD’s drug development platform and expertise to accelerate the development of much-needed therapeutics that address neglected global diseases, while at the same time NGDI-UBC will ensure reasonable, fair and affordable access for developing countries,” said Dr. Kishor M. Wasan, director and co-founder, NGDI-UBC and professor, Faculty of Pharmaceutical Sciences, UBC. “Any joint project approved by CDRD will be developed within the context of UBC’s Global Access Principles, which was an important criteria for our group,” added Dr. Wasan. “NGDI-UBC brings to CDRD an extensive network of expertise that extends across broad disciplinary boundaries. This partnership will augment our ongoing drug development
efforts, including some projects already underway with world leading scientists in the area of neglected global diseases,” said Karimah Es Sabar, senior vice president, Business & Strategic Affairs at CDRD. For example, Drs. Bill Mohn and Lindsay Eltis – both professors from the Department of Microbiology & Immunology at UBC – are jointly working on a project that addresses Tuberculosis (TB), which has been identified by the World Health Organization as a critical
neglected global disease. Their development work on the “Identification of small molecule inhibitors of cholesterol degradation as a therapeutic approach to the treatment of Tuberculosis” has been enabled by the drug development platform at CDRD. “Collaborating with CDRD has provided Dr. Eltis and I with the access to the drug development infrastructure and expertise required to turn out a bench-top assay into a high-throughput screen,” said Dr. Bill Mohn.
Patrick Deane
Government of Canada unveils research lab in Hamilton A new, $40-million, state-ofthe-art federal research lab has officially opened its doors in the McMaster Innovation Park in Hamilton. With its start-up and operating costs funded by the federal government, the CANMET Materials Technology Laboratory (CANMET-MTL) is expected to become a hub of research excellence. The Honourable Christian Paradis, Minister of Natural Resources, was joined by Bob
Bratina, Mayor of Hamilton; Patrick Deane, President of McMaster University; and Zach Douglas, President of the McMaster Innovation Park, at the official ribbon-cutting ceremony for CANMET-MTL. “Our Government’s investments in technology and innovation demonstrate our commitment to working with industry and academia to develop ‘made-in-Canada’ technological know-how,”
said Minister Paradis. “This new facility will deepen Canada’s technological capacity in new materials research and strengthen the long-term competitiveness of our manufacturing base, including Canada’s energy, automotive and steel industries.” “CANMET’s move to McMaster Innovation Park represents a huge boost for the region’s and country’s economic development and pros-
perity,” said Patrick Deane. “Its central location in the heart of the manufacturing sector, combined with its proximity to McMaster’s research facilities and expertise, has created a dynamic materials and manufacturing research cluster. Not only will this help to keep Canada’s industries competitive on the global scale, it will ensure that we attract and train the best students and researchers.”
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March 2011 Laboratory Focus www.bioscienceworld.ca
news
Dr. Rob McMaster
Bc cLinicAL reseArcH infrAsTrucTure neTwork LAuncHed To ATTrAcT significAnT invesTMenT in cLinicAL reseArcH in BriTisH coLuMBiA
Canada spends more than $500 million a year on clinical trials. Now through a new innovative collaboration, the
province of B.C. is positioning itself to attract a greater portion of the funds. In 2008, an estimated $540 million was invested in clinical research activity in Canada, but almost 89 per centof this research and development spending was in ON and QC. In order to therefore build a ‘friendlier climate’ and more streamlined process to attract an increased proportion of this investment, the BC Clinical Research Infrastructure Network (BCCRIN) has now been launched. BCCRIN will assist in firmly establishing B.C. as a global leader for clinical research, ultimately attracting increased investment to B.C. The BCCRIN is a collaborative partnership of provincial health authorities, universities, industry associations
and funding agencies, a first of its kind, committed to the harmonization of key clinical research and clinical trial requirements and to building gold standard capabilities to support clinical research. The goal of the Network is to establish B.C. as a premier location for advancing clinical and translational health research. “This innovative collaboration will lead to a unique clinical trials and research platform, making B.C. a key go-to place for conducting clinical trials and research – unlike any other in North America - gathering important health outcomes data,” says Dr. Simon Pimstone, president & CEO Xenon Pharmaceuticals and vice chair of the BCCRIN executive management team. Most importantly, Pimstone believes this
network will leverage the significant investment the province has already made into the health system and create new high paying R&D jobs. BCCRIN has already signed its first Memorandum of Understanding between six major research organizations; The University of British Columbia, Children’s and Women’s Health Centre, Providence Health Care, Vancouver Coastal Health, British Columbia Cancer Agency and Fraser Health Authority. “This agreement is the first step toward harmonization of the negotiation and acceptance of industry-sponsored clinical trials among these organizations and will give us a competitive advantage in BC” says Dr. Rob McMaster, chair, Executive Management Team, BCCRIN.
scientists eXPlore linK betWeen genes, antisocial beHaVior and cHolesterol Could a person’s ability to make cholesterol be linked to antisocial behaviour? Two B.C. scientists are exploring the
X Continuing
genetic pathways of a small group of individuals who carry a change in a gene that may elicit adverse behavioural reactions to cholesterol-lower-
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ing medications. This research will help pave the way for scientists to look at the links between genes and mental health, ideally resulting in targeted or personalized treatment for those suffering with mental health issues. Dr. Cornelius Boerkoel at the Child and Family Research Institute and Dr. Marco Marra of Canada’s Michael Smith Genome Sciences Centre at the BC Cancer Agency, are looking at a small target population who experience antisocial behaviour and aggression as a side effect of taking “statins,” a drug commonly prescribed to treat high cholesterol. Funded by Genome BC as part of its Strategic Opportunities Fund ($120,000), the Child and Family Research Institute ($50,000) and the Scottish Rite Foundation ($70,000), Drs. Boerkoel and Marra are examining cells from a group of individuals who exhibited anti-social behaviours after taking statin drugs. A series of biochemical tests will be done to determine if these individuals produce cholesterol differently. If they do, scientists will search for any genetic mutations that influence the way that these individuals make cholesterol. “This study shows the power of personalized medicine,” says Dr. Boerkoel. “If a psychiatrist or doctor could test someone with behavioural problems to see if they have an issue with cholesterol production, these patients could potentially be treated with specific drugs in a dosage that avoids or lessens the undesirable side-effects.” Dr. Boerkoel notes that as a general category, the economic impact to society could be huge if mental health
issues could be understood on a genetic level. Medical therapies could be targeted to the needs of the individual, with genomics removing the “guesswork” that is currently involved. “Many of the most exciting genomic advances are in the field of personalized medicine,” notes Dr. Alan Winter, president and CEO of Genome BC. “This will benefit patients as medical treatments can be tailored to their unique biology but it will also allow us to spend our health care dollars in a more sustainable and effective manner.” The researchers will look at 20 individuals who developed antisocial behaviours after they began treatment with statins and subsequently recovered normal social behaviour once they stopped taking the cholesterollowering drugs. Drs. Boerkoel and Marra hope that the results of this research will eventually help physicians predict who can safely use cholesterol-lowering drugs, and who should not. By the end of this study in 2012, diagnostic tests for patients may be ready. With an estimated 7.8 per cent of the Canadian population using statins and with statin use expected to increase as the national population ages, understanding how the drug interacts with the mental health of patients will be of interest to those suffering from diseases caused by abnormal cholesterol levels. This research will also provide new insight into understanding drug interactions overall, an area that is looked at in all clinical trials and is necessary for the approval of any drug for sale in Canada.
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March 2011 Laboratory Focus www.bioscienceworld.ca
APPoinTMenTs fer numerous benefits to patients throughout the world.
Theralase Technologies Inc. announces the appointment of Dr. Arkady Mandel as chief scientific officer. Dr. Mandel earned his designation as a medical doctor from the Moscow State Medical University in 1978. His medical residency included internships in: dermatology, infectious diseases, urology and venereal diseases at the Central Research Institute of Dermatology and Venerology in 1980, followed by a Ph.D. from the same institution in 1982. Dr. Mandel was then awarded in recognition of his scientific knowledge, original research, publications and extensive contributions to the field of clinical medicine the highest academic research degree in science, that of a Doctor of Science. Dr. Mandel’s Doctor of Science accreditation majored in: biochemistry, microbiology, immunology, biophysics, and photobiology, and was awarded jointly from the Academy of Sciences and the U.S.S.R. Ministry of Public Health in 1989. He is also one of the key founders of the therapeutic use of lasers in dermatology and other areas of clinical medicine, as well as the originator and developer of phototherapy methods that of-
James C. Mullen has been named as Patheon’s chief executive officer, effective immediately.
Mr. Mullen has also been appointed a director of Patheon’s Board of Directors. Ramsey Frank, Patheon’s chairman stated, “The Board of Directors is very pleased that Jim Mullen will be joining Patheon. Mr. Mullen’s extensive pharmaceuti-
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Protox Therapeutics Inc. announces the appointment of William Rohn and Amit Sobti to the company’s board of directors. Rohn has over 30 years of experience as a senior executive in the pharmaceutical and biotech industry. He retired in January of 2005 from the position of chief operating officer at Biogen-Idec, and played an instrumental role in the $6.8 billion merger of IDEC Pharmaceuticals and Biogen Inc. Prior to serving as COO of the combined company, Bill was the president and chief operating officer of IDEC Pharmaceuticals where he helped transform IDEC from a small research organization into a very successful, biotechnology company. Rohn prior to joining IDEC spent approximately 25 years in the pharmaceutical sector in a variety of commercial operating roles of increasing responsibilities at Abbott Laboratories, Bristol-Myers Squibb Co., and Adria Laboratories (now part of Pfizer). In addition to his role at Protox, he serves on the Board of Directors of Cerus Corporation, Intellikine, Cebix Inc., and the La Jolla Institute of Allergy and Immunology. Amit Sobti is a principal with Warburg Pincus where he focuses on investments in health-
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cal manufacturing background and proven track record of driving growth and profitability give us confidence that, under his leadership, Patheon will be able to realize its full potential as an industry leader.” Mr. Mullen was most recently with Biogen Idec, Inc., where he held the position of CEO and president for 10 years. Biogen Idec was formed from the merger, led by Mr. Mullen, of Biogen, Inc. and Idec Pharmaceuticals. Prior to the merger, Mr. Mullen was the CEO and president of Biogen, Inc. from 2000 to 2002, and chairman, CEO and president until 2003. Prior to that, Mr. Mullen held various operating positions at Biogen, including vice president, Operations; and several manufacturing and engineering positions over a nine-year period at SmithKline Beckman, Inc. In addition, Mr. Mullen’s 30-year career includes extensive experience in pharmaceutical and biotech manufacturing, engineering, sales, marketing, mergers and acquisitions. His breadth of industry experience includes biotechnology, pharmaceuticals and specialty chemicals. Mr. Mullen holds a Bachelor of Science in Chemical Engineering from Rensselaer Polytechnic Institute, and a Master of Business Administration from Villanova University.
4/26/2010 12:56:28 PM
care. Prior to joining Warburg Pincus, he worked at Rhône Capital, a mid-market private equity firm, and at Merrill Lynch in the Mergers & Acquisitions group. Sobti received an A.B. in Business Economics and an A.B. in Computer Science from Brown University. In addition to Protox, Amit also serves on the Board of Directors of ReSearch Pharmaceutical Services, Inc. Afexa Life Sciences Inc., announces that Tracey Ramsay has agreed to join the company as chief marketing officer and senior
vice president Sales. Ms. Ramsay will serve on Afexa’s executive leadership team, and will report directly to the chairman and CEO. Before joining Afexa, Ms. Ramsay held positions as vice president of Sales, vice president Marketing and general manager within large multi-national pharmaceutical and healthcare companies. Her strategic and operational management skills have contributed to the development of organizational structures that have realized increased market share for products having complex regulatory requirements. Stewart Davis has been appointed to the role of chief operating officer at Healthscreen Solutions IncDavis has over 30 years of experience in the technology industry and in areas of business including finance, sales and marketing, operations, technology development and executive roles of chairman, CEO and president. Healthscreen also announces that Ms. Teresa Brzozowski, Heathscreen’s current chief operating officer and Ms. Anastasia Chodarcewicz, Heathscreen’s chief financial officer, will be leaving the Company, with both completing their transitions in the coming months. The company also expects to fill the roles of chief financial officer as well as a new role of chief information officer within the next few months.
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Laboratory Focus March 2011
Pharma Notes Cytochroma (Markham, ON) announces the initiation of a repeat-dose safety and efficacy study of CTAP101 capsules in patients with vitamin D insufficiency, secondary hyperparathyroidism (SHPT) and stage 3 chronic kidney disease (CKD). The newly initiated trial is a randomized, double-blind, placebo controlled, multisite study designed to evaluate the safety, efficacy, pharmacokinetics, pharmacodynamics and tolerability of CTAP101 capsules, administered at various daily doses, in approximately 60 patients. The endpoints in this study will include vitamin D status, adverse events, physical and clinical laboratory assessments, and changes in serum calcium, phosphorus and intact parathyroid hormone (PTH). Endo Pharmaceuticals (Newark, DE) and Bioniche Life Sciences Inc. (Belleville, ON) announce the enrollment of the first patient in the second Phase 3 clinical trial of Urocidin™. The trial is a randomized, active-controlled, open-label, multi-center study with a blinded endpoint assessment designed to compare UrocidinTM with mitomycin C in the intravesical treatment of patients with BCG recurrent or refractory non-muscle invasive bladder cancer. It is estimated that 450 patients will be enrolled for this new trial at approximately 120 clinical sites worldwide. Stem Cell Therapeutics Corp. (Calgary, AB) has been granted a patent by the U.S. Patent and Trademark Office -U.S. Patent 7,884,072- entitled, “Prolactin induced increase in neural stem cell number.” The claims contained within this issued patent cover methods of using an effective amount of prolactin to increase stem cell numbers in mammals suspected of having neurological diseases. Helix BioPharma Corp. (Aurora, ON) has received approval for its investigational new drug (“IND”) application from the United
States Food and Drug Administration to perform its planned U.S. Phase I clinical safety and tolerability study of its lung cancer drug candidate L-DOS47. L-DOS47 is the Company’s first therapeutic immunoconjugate drug candidate under development based upon its novel DOS47 platform technology, which is designed to modify the microenvironmental conditions of cancer cells in a manner that leads to their destruction. L-DOS47 is intended to offer an innovative approach to the first-line treatment of inoperable, locally advanced, recurrent or metastatic non-small cell lung cancer. The FDA has completed its review of the IND and concluded that it is acceptable for Helix to proceed with the study, contingent on Helix providing an amended version of the clinical protocol beforehand, reflecting several minor changes that FDA stipulated during the course of the IND review. The company will now proceed with its remaining pre-study logistical preparations, including preparation and filing with the FDA of the required clinical protocol amendment, with a view to commencing clinical site initiation and patient recruitment activities late spring to early summer of this year. Dalton Pharma Services, (Toronto, ON) a privately
owned Canadian pharmaceutical services provider to leading pharmaceutical companies, has entered into a Manufacturing Services Agreement with Oncovir Inc., a specialty pharma company based in Washington DC, dedicated to the development of nucleic-acidbased clinical therapies for cancer, infectious, immune, and degenerative disorders. Dalton Pharma Services will provide API manufacturing and aseptic fill/finish services under cGMP, for Oncovir’s collaboration with the Cancer Vaccine Acceleration Fund (CVAF), a joint initiative between the Cancer Research Institute (CRI) and the Ludwig Institute for Cancer Research (LICR). CVAF has completed a new investment agreement with Oncovir, Inc., to enable the production of Oncovir’s immune activator Hiltonol®. Warnex Inc. (Laval, QC) announces that its Warnex Medical Laboratories division will serve as a central laboratory across Canada for Genzyme Canada Inc.’s (Ottawa, ON) Lysosomal storage disorders testing program. This program will assist physicians in diagnosing Fabry (male), Gaucher, Pompe and Mucopolysaccharidosis Type I (MPS I) diseases. Medwell Capital Corp. (Edmonton, AB) announces that it has committed to
invest up to $2,000,000 in Mimetogen Pharmaceuticals Inc. (Montréal, QC), a privately-held, clinical-stage company developing a treatment for dry eye disease. Medwell Capital participated in a Series B equity financing with existing Mimetogen investors, iNovia Capital, MSBi Valorisation and VIMAC Milestone Medica. As part of the financing, Nitin Kaushal, executive vice president of Medwell will join the Mimetogen Board of directors. Medwell Capital will also assist Mimetogen and the current investors with advisory services in potential partnering and financing efforts. Mimetogen’s lead drug candidate for the treatment of dry eye disease, MIM-D3, is a small molecule mimetic of nerve growth factor (NGF). NGF is a naturally occurring protein in the eyes that is responsible for the maintenance of corneal nerves and epithelium, mucin and tear production. Isotechnika Pharma Inc. (Edmonton, AB) announces that Lux Biosciences, Inc. (Jersey City, NJ) has commenced its Phase 3 trial using voclosporin for the treatment of non-infectious uveitis, a leading cause of vision loss and long-term disability. The study is a six-month randomized trial of voclosporin versus placebo in patients with active non-infectious intermediate,
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posterior, or pan-uveitis. This Phase 3 trial will involve 150 patients in North America and Europe. Lux is conducting this additional Phase 3 trial as outlined in the Complete Response Letter received in August, 2010, from the FDA. In 2006, Isotechnika granted Lux worldwide rights to develop and commercialize voclosporin for ophthalmic diseases. In return, Isotechnika will receive development milestones payments, as well as royalties on net sales. Voclosporin (branded as Luveniq™ by Lux) was accepted for review by the European Medicines Agency (EMA) in March 2010. The product has received Orphan Drug designation in both Europe and the U.S. for the treatment of non-infectious uveitis. Canadian specialty pharmaceutical company Paladin Labs Inc. (St. Laurent, QC), announces that Health Canada has approved Abstral®. Abstral® is a novel, rapidly-disintegrating, sublingual (under the tongue) formulation of fentanyl, a well-established opioid used for the management of episodes of breakthrough pain experienced by cancer patients who are already receiving opioid analgesics for chronic pain. Paladin obtained the Canadian rights from ProStrakan Group plc in December 2008.
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March 2011 Laboratory Focus www.bioscienceworld.ca
Feature
Cascade ultrafiltration system
for high throughput therapeutic
protein
purification
Photo: Sartorius Laboratory
By Mukesh Mayani T h e r ap u r e B i o pha r ma I n c .
Introduction Therapeutic proteins (TPs) are purified using RIPP (Recovery, Isolation, Purification and Polishing) scheme in the biopharmaceutical industry. Recovery and isolation steps are performed using relatively low resolution methods such as microfiltration, depth filtration, precipitation and centrifugation. For purification, high resolution methods such as adsorption and chromatography (e.g. protein A affinity, hydrophobic interaction or ion exchange) are employed. Usually, these purification methods are slow and expensive resulting significant burden on downstream processing and higher cost of the products.1
Figure 1
Major conventional membrane separation processes used in biopharmaceutical industry. Diafiltrate
Solvent
Permeate
Retentate
Buffer Membrane module
Tank Pump
(A) Batch concentration
Membrane module Tank Pump (B) Diafiltration/buffer exchange
Membrane module Tank Pump (C) Steady-state fractionation
Photo: Sartorius Laboratory
www.bioscienceworld.ca
Ultrafiltration membranes are integral part of biopharmaceutical industries and have been used at several stages to separate macromolecules from smaller solutes such as salts, water, sugars, amino acids and proteins.2 In downstream processing, they are typically applied for protein concentration (i.e. the removal of solvent from solutions of macromolecules), desalting and diafiltration (i.e. the removal of salts and other low molecular weight compounds), buffer exchange (i.e. the exchange of solvent molecules), and in some cases, for fractionation (i.e. the separation of one protein from another) (see Figure 1). However, these operations are aimed for rapid processing using single or multiple membrane unit(s) configured in traditional manner. Although the membrane making technology has been improved over the years, the benefit in purification has not been seen as a consequence of the conventional manner of application. The limitation of sharp membrane cut-off has been seen as the limiting factor for suitability of membranes in protein purifications. However, this limitation can be offset by combining multiple membrane units. It has been found that multiple membrane unit can be operated to achieve better overall resolution of a target protein and thus purification performance can significantly improved.3-6 The purity and recovery could be complemented to chromatographic purification in some niche applications.7 The author has investigated suitability of cascade ultrafiltration systems for several systems4,5 and made specific observations in regards to fundamental characteristics of ultrafiltration cascade systems and suitability at larger scale.
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Laboratory Focus March 2011
Figure 2 shows a schematic of a typical three-stage cascade ultrafiltration used for fractionation of two proteins in continuous manner. The membrane 1 (designated as M1) completely retains protein A and membrane 3 (designated as M3) to product
B. The membrane 2 (designated as M2) preferentially transmits protein B while it has molecular weight cut-off (MWCO) smaller than M1. The feed is introduced into the cross flow loop across M2 for fractionation of A and B. The permeate from M2 is sent
news to retentate cross flow circuit across M3, whereas the controlled flow stream from the cross flow loop across M2 is sent into the cross flow across M1. The permeate from M1 is introduced into the cross flow
circuit across M2 as product B recovery stream. The permeate drawn from M3 is essentially free of protein B and function as in situ generated sweeping buffer, which is introduced into the cross flow
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A system of ultrafiltration membrane units, integrated to make a bigger unit in which separation characteristics of individual units are inter-dependent. The membranes are configured to make an overall system which is suitable to achieve a desired objective of protein purification. The overall cascade ultrafiltration system becomes compact, low-energy consuming, scalable and provides operational flexibility.
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March 2011 Laboratory Focus www.bioscienceworld.ca
feATure figure 2
cascade ultrafiltration configuration for fractionation of two proteins.4
Overall retained product A
Overall permeate product B
M2
M1
M3
M2
In situ sweep buffer Feed M1 = Membrane 1, M2 = Membrane 2, M3 = Membrane 3
across M1 for recovery of product B from overall retentate. The bleed flow drawn from the retentate cross flow circuit of M1 is the overall retentate product A while that drawn from retentate flow circuit of M3 is an overall permeate product B. In this design, the flow ratio of the overall retentate flow to permeate flow as well as value of flow into M1 flow circuit from M2 cross flow circuit can have significant effect on purification and productivity. These parameters can be optimized to achieve optimal purification.
Why cascade ultrafiltration system give better resolution? Each ultrafiltration membrane constituting cascade system can be configured and operated at a permeate flux corresponding to its high selectivity in the pressuredependent part of the filtrate flux curve. Thus, it can provide high resolution purification while maintaining the inherent high throughput and high yield characteristics of conventional ultrafiltration. Hence, the possibility of pro-
tein separation without being limited to relative size of proteins is a sharp contrast to the previous limit of having to separate solutes that differ by more than ten-fold in size, a limit which would no longer be required. An example is presented in reference 4, where a protein having molecular size 14.3 kDa (lysozyme) is purified from 17 kDa size proteins in continuous manner.
What are important characteristics of cascade ultrafiltration system? It provides the opportunity to combine several different separation steps into a single scalable unit operation, such as simultaneous purification and concentration. The integration of membrane modules provides the opportunity to generate buffer insitu and could recycle it for economy and better separation. In some cases, recycled buffer dilutes proteins and reduces concentration polarization as well as membranefouling effects. By using different MWCO membranes, and/or surface charge properties of membranes, one
can effectively improve resolution in a single-unit set up. Also, cascade provides the opportunity to carry out the separation process in batch, continuous, or semi-batch mode, depending on our requirements. It is also suitable for the fractionation of two proteins with negligible dilution.
How cascade ultrafiltration operation is different from conventional ultrafiltration? Preferably, cascade ultrafiltration units are operated in constant flux mode to achieve higher separation factor between two protein fractions. As the protein compositions are different in different membranes constituting cascade system, the permeate flux, i.e. permeate flow need to be optimized to achieve higher retention or permeation of specific protein component across each membranes. Usually, permeate pumps are employed to achieve constant permeate flux while use of cross flow pump limits effect of concentration polarization or fouling over the membrane surface.
Each ultrafiltration membrane constituting cascade system can be configured and operated at a permeate flux corresponding to its high selectivity in the pressure-dependent part of the filtrate flux curve. What are limitations of cascade ultrafiltration? The system needs optimization of operating conditions and membrane configuration. For continuous processing, the system works better when protein concentration is as low as one to two per cent. However, the in situ generation of sweeping buffer can be of significant importance in maintaining low protein concentration in the flow circuits. Also, the system operational complexity is more as a consequence of permeate and retentate pumps.
References 1. van Reis R, Zydney AL. Bioprocess membrane technology. J. Membr. Sci. 2007;297:16-50. 2. Ghosh R. Protein Bioseparation Using Ultrafiltration: Theory, Applications and New Developments, London, Imperial College Press/ World Scientific Publishing Pte Ltd., 2003. 3. van Reis R, Gadam S, Frautschy LN, Orlando S, Goodrich EM, Saksena S, Kuriyel R, Simpson CM, Pearl S, Zydney AL. High performance tangential flow filtration. Biotechnol. Bioeng. 1997;56:71-82. 4. Mayani M, Filipe CDM, Ghosh R. Cascade ultrafiltration systems – Integrated processes for purification and con-
centration of lysozyme. J. Chromatogr. Sci. 2010;347:150-158. 5. Mayani M, Mohanty K, Filipe C, Ghosh R. Continuous fractionation of plasma proteins HSA and HIgG using cascade ultrafiltration systems. Sep. Purif. Technol. 2009:70:231-241 6. Mohanty K, Ghosh R. Novel tangential-flow countercurrent cascade ultrafiltration configuration for continuous purification of humanized monoclonal antibody. J. Membr. Sci. 2008;307:117-125. 7. Lightfoot EN. Can membrane cascades replace chromatography? Adapting binary ideal cascade theory of systems of two solutes in a single solvent. Sep. Sci. Technol. 2005;40:739-756.
Mukesh Mayani (Ph.D., MCIC) is Research Scientist (Drug Development) at Therapure Biopharma Inc., a Canadian CDMO and involved in developing downstream processes for purification of complex therapeutics. He has several years of experience in drug manufacturing and bioseparations engineering. He holds the Ph.D. degree in Chemical Engineering from McMaster University, Canada and M.Tech. from Indian Institute of Technology, India.
Learn more about High throughput Protein Purification on our Whitepapers Web Portal at www.bioscienceworld.ca
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Laboratory Focus March 2011
feature B y Da v i d K n o r r , Z a c ha r y Va n D e n H e u v e l , M a r c B e ba n 1
2
1
High throughput purification of human IgG using the
Agilent Bravo 96AM
and AssayMAP protein A cartridges Introduction
Abstract To address a growing desire for robust, high-throughput chromatography capability, Agilent Technologies has developed a 96channel pipetting head to enable microchromatography on the Bravo liquid handling platform using AssayMAP protein purification cartridges from Biosystem Development. The system can operate using direct fluid displacement for chromatography applications, or air displacement for conventional liquid handling. Early results using the system to purify immunoglobulin from artificially constructed samples show the system can purify between 1 and 100 µg of target protein when presented in backgrounds as high as 10 mg/ml of non-specific protein. Recovered protein quantities accurately reflect input quantities, and these results are repeatable over a number of purifications using used or un-used cartridges.
The rise of biologics as important pharmaceutical agents has driven an ever-increasing demand for protein analysis methods that are precise, sensitive, and amenable to high throughput. These methods are used to analyze complex samples from throughout the biopharmaceutical discovery process, from research samples taken from protein expression systems to biological samples present in serum to production cell lysates and cell culture supernatants. In typical workflows, HPLC and immunoassays are used to affinity purify specific proteins from complex samples and quantify using absorbance, fluorescence, or chemiluminescence. While these methods have been successfully used for years, a significant challenge has been in adapting these methods to the demands of high throughput analysis where concerns of sample capacity and reagent use are prominent. The Agilent Bravo with AssayMAP® technology is a simple, precise, and high-throughput platform for microscale purification and preparation of polyclonal or monoclonal antibody (MAb) from bioprocess samples. The 96AM liquid handling head utilizes AssayMAP cartridges with the same protein A chemistry as traditional affinity HPLC and adds advanced liquid handling of the Agilent Bravo to enable protein purifications from complex matrices. This automated platform allows for a full range of high throughput, highly parallelized liquid handling operations, including precision flow rate control to enable true chromatographic separation of the
target molecule in low sample volume. The result is a robust system for multiplexing up to 96 samples in a single run. Here we present results showing system performance purifying human immunoglobulin G (hIgG) from samples with different concentrations of background protein.
Materials and Methods Reagents: IgG from human plasma (#16-16-090707, Athens Research & Technology, Athens, GA, USA) was diluted to 4 mg/ml in PBS (Sigma). Fish gelatin from cold water fish (FGel, Sigma, #G7041) was reconstituted in PBS at a stock concentration of 20 mg/ml. Bound protein was eluted in 100 mM glycine (pH 2.5, Fisher Scientific, #G46). Phosphate buffered saline (PBS) was diluted from 10X stock (Sigma, #P5493). Protein A purification cartridges were obtained from BioSystem Development. Instrumentation: Experiments were carried out using a standard Agilent Bravo with a 96AM liquid handling head and an Agilent 96-channel wash station and pump module controlled by VWorks software. Absorbance values were collected at 280 nm using a Varioskan Flash multimode reader (Thermo). Electrophoresis was performed using Agilent Protein 230 chips (Agilent Technologies # 5067-1518) run on an Agilent 2100 Bioanalyzer with 2100 Expert software. Workflow: Cartridges were preconditioned by priming with 125 µl
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March 2011 Laboratory Focus www.bioscienceworld.ca
Feature Figure 1
Figure 2 [FU] 500
1
0.8
400
0.6 A280
300
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200 FGel background (mg/ml) background (mg/ml)
02 0.2
0
5
100
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PBS at a flow rate of 33 µl/s, then equilibrated by aspirating an additional 50 µl of PBS at 0.41 µl/s. Cartridges were loaded by aspirating 50 µl of sample at a rate of 0.1 µl/s, then washed by aspirating 50 µl of PBS at a rate of 0.41µl/s. Cartridges were dismounted and then the probes were washed 3 times with PBS. Human IgG was eluted by aspirating 50 µl of elution buffer into the probes, mounting the cartridges, then dispensing the syringe contents at a rate of 0.1 µl/s into a 96-well microtiter plate (Greiner µv Star, # 675801). Following elution, the cartridges were flushed with additional PBS, dismounted and the syringes washed. Linearity was measured by creating 3 sets of 2-fold serial dilutions of hIgG prepared with final concentrations of FGel at 0, 5 and 10 mg/ml. HIgG concentrations for each set were 2, 1, 0.5, 0.25, 0.125, 0.0625, 0.03125 and 0.015625 mg/ml. Each dilution set was introduced to the system using a 12-well sample reservoir (Porvair Sciences, Ltd., # 390012) with each well corresponding to a column of 8 syringes. A single concentration was placed into each of 8 wells and 1X PBS was added to a ninth well as a control. Following purification as outlined above absorbance values for each set of dilutions were averaged and plotted as shown in Figure 1. Purity was determined using the Bioanalyzer to run sets of un-purified and purified products from individual cartridges. Four µl of sample
was mixed with 2 µl of non-reducing denaturing solution, heated, then diluted with 84 µl of de-ionized water and loaded onto an Agilent Protein 230 chip which was run as described in the Agilent Protein 230 Kit Guide (P/N G2938-90054). Figure 2 shows the super-imposed output from four lanes. To examine reproducibility and robustness of the assay, a set of samples was constructed with 0.1, 0.4, or 2 mg/ml hIgG in a background of 10 mg/ml FGel. A sample plate then was prepared such that each dilution filled 4 columns (i.e., A1 – H4, A5-H8, or A9-H12). This plate was used during six successive purification runs. Between each run, the sample plate was rotated 180° so that cartridges used to purify high or low amounts of hIgG in one run would be used for the most different concentration in the next run, and so on. After four runs, the cartridge box was replaced and two more runs were performed.
Results and Discussion: Performance of the system was examined by purifying different concentrations of hIgG that were presented in different backgrounds of a contaminating protein. Linearity of the response was nearly perfect throughout the 1 to 100 µg binding capacity of the cartridges. Purified products co-migrated with hIgG during capillary electrophoresis. In addition, purification results were consistent over multiple assays, and for different cartridges.
25
30
35
40
[s]
Superimposed eletropherogram traces from Protein 230 chips. 166 kDa peak indicates expected position for hIgG. Arrows labeled M indicate upper and lower protein ladder markers.
Figure 3
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Run 1 Ͳ fwd Run 1 Run 2 Ͳ rev
1
Run 3 Ͳ fwd Run 4 Ͳ rev
0.8
A2800
Absorbance values of eluates from Protein A cartridges loaded with hIgG and different concentrations of FGel. R2 values for the three different sample sets, 0, 5, and 10 mg/ml background protein, were 0.9997, 0.9998, and 0.9992 respectively Average values for each concentration were calculated from 8 readings. Error bars indicate standard deviation.
20
Run 5 Ͳ fwd Run 6 Ͳ rev
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IgG starting concentration (mg/ml)
Run-to-run reproducibility of cartridge-based purification of hIgG. Six purifications were run using 96 cartridges and the same sample input plate containing three different concentrations of hIgG along with 10 mg/ml FGel. Between each run the sample plate was rotated 180° (relative rotation is indicated next to each sample in the legend). Average absorbance values for each input concentration (24 samples) are given including standard deviation. Runs five and six used a separate set of cartridges.
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Laboratory Focus March 2011
feATure Results in figure 1 illustrate ability of the 96AM platform to purify protein directly proportional to input of specifc target presented. Yields of hIgG were linear throughout the range of target binding capacity for the cartridges. This performance was obtained even with nonspecific backgrounds as high as 10 mg/ml, which approximates that seen with many biological samples. Purified samples examined using electrophoresis under native conditions maintained the expected major peak at approximately 166 kDa while non-specific material was minimized. Sample-tosample results throughout six purification runs showed excellent agreement in the amount of eluted product. Results were similar for new and used cartridges, regardless of whether they had been used to purify widely different amounts of target in a previous run. This indicates robustness in both the protocol and the hardware, including cartridge production. The Agilent Bravo with AssayMAP technology provides a robust system for hIgG titer in support of biopharmaceutical discovery and development. The 96AM head is designed to maintain syringe dead volumes at less-than 500 nl, which is important in eliminating air bubbles and allows direct displacement of fluid to maintain constant flow rate regardless of column resistance. The direct displacement mode can be used with either AssayMAP cartridges or bare probes. By controlling whether cartridges are mounted during aspirate and dispense cycles, the system can dictate uni-directional flow through the cartridges. The head can also use pipette tips in airdisplacement mode, delivering 2 µl at ±5% CV, which is identical to the Agilent Bravo 96LT head. While the normal velocity range of 1-500 µl/s is maintained for use with pipette tips, in direct-displacement mode flow rates can be controlled to as low as 1 µl/ minute to address challenging separations. The combination of flow control with direct displacement fluid handling in a multichannel system enables high throughput microchromatography. Two critical factors for developing a successful chromatography method are quan-
titative binding of desired targets, and efficient removal of non-specific material. Flow rate control is of key importance for both factors to optimize interactions between the sample and column bed material. This is especially important for assays which rely on
enzymatic reactions. Because the 96 AM system combines a wide range of flow rates with high-quality microscale media cartridges it will be useful for developing additional affinity purification methods as well as enzyme-based applications such as immunoas-
says and glycan analyses. AssayMAP® is technology patented by BioSystem Devel-
Reply card #4412
opment. AssayMAP® is a registered trademark of BioSystem Development.
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14
New Products Conical centrifuge tubes Thermo Fisher Scientific Inc. introduces new 15 and 50ml Thermo Scientific Nunc conical centrifuge tubes. The 15/50 ml conical centrifuge tubes are ideal for any laboratories within academia, government, biotechnology and pharmaceutical research. Incorporating a new plastic rack design that is reusable, collapsible and recyclable, the 15/50 ml tubes are offered with an environmentally friendly, space-saving storage solution. This design provides a cleaner option for use in cell culture and biological safety cabinets by reducing any potential risk of particle contamination. The new tubes also feature the largest writing area in the industry, which enables researchers to clearly label their research for increased sample traceability. With a leak-proof design the tubes are certified USP Class VI, non-pyrogenic, non-cytotoxic and RNase/DNase-free to ensure consistently high-quality results are obtained. The 15/50 ml tubes also have a higher RCF rating, which enables a broad range of applications requiring low-speed to super-speed centrifugation protocols
Reply Card #4413
Analyzers
Oscilloscopes AEMC® Instruments introduces its’ third generation of self-contained, hand-held, two and four-isolated-channel oscilloscopes (100MHz and 200MHz bandwidth models are available). The oscilloscope features five complementary tools in one, an Oscilloscope, FFT analyzer, 4-channel TRMS multimeter, harmonic analyzer and a recorder. The Model OX 7100 (100MHz) and OX7200 (200MHz) series Oscilloscopes are rugged and ergonomic instruments that can be used in both the laboratory and in field testing. Ideal for field use, they utilize the patented, new system of “plug-and-play” accessories, isolated measurement channels and a range of remote management capabilities. The Ethernet link lets you remotely control the oscilloscope without loading any software on your PC. The large 320 x 240 full color LCD touch screen provides detailed graphical and alphanumerical representations of all measurements and also functions as a touch screen. The various “Windowslike” menus can be opened or pulled down and executed, using the convenient stylus. The stylus can also be used for direct action on graphic elements such as cursors, triggers and zooming.
Reply Card #4415
Cartridges Biotage announces two new additions to its SNAP XL family of cartridges for large scale and development purification. Released in both 750g and 1500g sizes, the new cartridges offer solutions for reverse phase chromatography (KP-C18-HS) and also optimized silica for the separation of amines (KP-NH). The new cartridge sizes address a growing need for 100g+ scale purifications and offer chemists increased efficiency while reducing running costs. Additionally, the application of reverse phase flash chromatography and the separation of amines are growing trends in pharmaceutical drug development.
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March 2011 Laboratory Focus www.bioscienceworld.ca
Reply Card #4416 Shimadzu Scientific Instruments introduces the TOC-L Series of analyzers for total organic carbon testing in aqueous samples. With a wide sample range from 4 μg/L to 30,000 mg/L, the TOC-L is suitable for analyzing ultra-pure to highly contaminated samples of wastewater, brine water, seawater, drinking water and pharmaceutical water. Consisting of four models, including PC-controlled and standalone versions, the TOC-L uses Shimadzu’s 680° C combustion catalytic oxidation method to efficiently analyze all organic compounds. It features automatic sample acidification and sparging, as well as an automatic dilution function that reduces sample salinity, acidity and alkalinity. This significantly extends the use of catalysts and combustion tubes. The series also features variable syringe sizes when the sample volume is limited. High-precision mass flow controllers ensure uninterrupted carrier gas for accurate analysis. A zero-maintenance Peltier cooler used for maximum water vapour removal ensures accurate analysis. In addition, an on-board air purifier may eliminate the need for high-purity air during testing. Optional salt kits permit 12 times more salt to be analyzed before maintenance is required. The ASI-L autosampler can use three different vial sizes for various applications, while the smaller OCT-L autosampler can use any vial size for up to eight or 16 samples. TOC-L models can accept particulates up to 500 microns or 800 microns with the optional particulate kit. For larger particles, solids, soils and sludge, the SSM-5000 is the ideal solution. The TNM-L can be added for simultaneous TOC and Total Nitrogen analyses without increasing the size of the footprint.
Reply Card #4414
SpectroSens Stratophase, a specialist in realtime chemical and biochemical measurement, has premiered its latest SpectroSens monitoring and data analysis control. Stratophase’s new device is a bench-top control centre capable of monitoring up to eight independent inline SpectroSens optical sensors. SpectroSens sensors employ an innovative technology that interprets changes in refractive index to provide real-time process monitoring. The new data monitoring unit provides a built-in touch-screen interface while reducing footprint by over 50 per cent. Due to its new ergonomic form and smaller size, the SpectroSens unit is perfectly suited for use in a range of environments, from a small process development laboratory up to industrial scale requirements. The multichannel capabilities of the device allow it to be connected to a number of SpectroSens sensors, whether in a single, multi-stage process or in situations where multiple processes are running in parallel.
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Laboratory Focus March 2011
ID Scribe Labware Identifier Thermo Fisher Scientific Inc., launches its new Thermo Scientific ID Scribe Labware Identifier for the consistent and legible labeling of storage tubes, vials and other common labware. Sample misidentification due to misread handwriting is eliminated. The easy-to-use ID Scribe™ works with nearly any labware, permanently and legibly marking it for fast and mistake-free sample identification.Markings on labware labelled with the ID Scribe lasts for years. The instrument is supplied with a selection of different pen colors and a custom pen holder. Users can effectively color-code specific samples for quick and easy identification.
Reply Card #4418
Temperature controller
New Products Data collector T&D Corporation introduces its new RTR-500DC, a handheld wireless data collector featuring a large, easy to read graphical display. The RTR500DC is ideal for applications where items to be monitored are in motion, or where physical access to the data logger itself is inconvenient or impractical. Examples might be display cases, mobile applications or outdoor use. The unit can monitor and download data from up to 224 separate loggers and stores up to 256,000 readings, which can then be uploaded to a PC via a USB connection. The RTR-500DC displays the data on a graphical display with zoom function. The unit includes a “search” mode for locating data loggers and a signal strength indicator. This pocket sized unit weighs only 4.4 oz and operates for over 100 hours on 2 AAA batteries. The transmission distance is up to 500 feet, line of sight, which can be extended with the use of wireless repeaters.
Reply Card #4421
Injector
Warner Instruments introduces its new CL-200 dual channel bipolar temperature controller for automatic control of two peltier devices. Accurately maintaining temperatures between -6° and 65°C with a single control, this model features a feedback thermistor switch that allows the user to select which thermistor is used for feedback control. Built-in protection for Peltier devices prevents overheating or freezing, while a low-noise power source makes the CL-200 ideal for sensitive electrophysiology applications. The CL-200 supplies 75 watts of power to each channel and is designed to control any Warner Instruments Peltier driven temperature control devices. Warner Instruments is a designer and manufacturer of biomedical devices for the electrophysiological, cellular and neurological sciences.
Reply Card #4419
Syringe pump drug and cell delivery system The new PHD ULTRA™ syringe pump drug and cell delivery system from Harvard Apparatus has been optimized to provide highly accurate and precise injections of low nanolitre to microlitre volumes of cells and drugs that must be delivered to specific spatial locations. The Harvard Apparatus PHD ULTRA™ Nanomite features foot pedal activation for hands-free injections. Its high resolution LCD touch screen and icon interface allows users to create and run simple to complex methods without a PC. This enables new and existing operators to easily retrieve and run any pre-defined delivery method, greatly enhancing injection repeatability and reducing the likelihood of user error. Though designed for fast bolus infusions, with high accuracy and precision, the PHD ULTRA™ Nanomite can easily deliver from low nanolitre up to tens of ml/min injections, particularly when combined with Harvard Apparatus micro needles as small as 37 gauge. The PHD ULTRA™ has flow ramping capability for superior continuous volume injections into organs, muscle tissue, cells and neurons with minimal physiological impact.
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VICI Valco’s new Cheminert C72 Ultra-high Pressure UHPLC Injector features a proprietary stator coating that permits pressures up to 15,000 or 20,000 psi. Many of the latest analytical techniques require systems that are capable of this much pressure. The injectors use the same mounting system as the widely used Cheminert C2 series HPLC injectors. The optional microelectric actuator determines accurate positioning without limit switches or customer adjustment. Computer control is facilitated via RS-232 or RS-485 interface, but it can also be controlled manually. The actuator is CE-certified, and includes an autosensing 110/230 VAC to 24 VDC universal power supply. All these features are built into a compact and lightweight package, available in four, six, eight and ten port configurations, and choice of .004”, .006” or .010” bore.
Reply Card #4422
Pipetting Head Hamilton Robotics introduces the TADM 96 Multi-Channel Pipetting Head, with aspiration and dispense monitoring technology in every channel. The new head is compatible with Hamilton’s MICROLAB® STARline of automated liquid handling platform and incorporates the company’s Total Aspiration and Dispense Monitoring (TADM) technology. Air pressure sensors are built into each channel, which monitors pipetting based on Hamilton’s unique air displacement technology. TADM monitors the pipetting steps in real time and gives users the opportunity to immediately react to problems like empty samples, clots or foam. TADM verifies and documents with a traceable digital audit trail to confirm that a sample has been successfully transferred, which is useful in regulated environments.
Reply Card #4423
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NEW PRODUCTS Catalog
System and Animal Origin Free (AOF) Collagenase, DNase, Neutral Protease, RNase and other enzymes for regenerative medicine, biopharma and vaccine production applications.
Worthington Biochemical’s new 2011-12 Catalog features enzymes, biochemicals and primary cell isolation kits for applications in life science research, diagnostics and biotechnology. New and traditional products are included with applications in primary cell isolation and cell culture, protein sequencing, enzymology and molecular biology. New products include the Worthington Hepatocyte Isolation
Reply Card #4424
Omega model HHM590 series The Omega model HHM590 series has over ten fully featured models to choose from. All clamp-on meters
include free set of safety test leads, 9V alkaline battery, type K beaded wire thermocouple (temperature models only) and complete operator’s manual. Each unit has a GS-Mark EN61010-1 approval voltage category III 600 V, pollution degree II, and an AC/DC Current Clamp. Other features include maximum data hold, peak Æ zeroERO functions.
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Laboratory Focus March 2011
MARCH 2011 March 13-18 PITTCON Conference & Expo Venue: Atlanta, GA Tel: 1-800-825-3221 Fax: (412) 825-3224 Email: info@pittcon.org Web: www.pittcon.org
March 14-15 Bio-Europe Spring 2011 Venue: Milan, Italy Web: www.ebdgroup.com/ bes/index.php
March 27-29 BioVision 2011 Venue: Lyon, France Tel: 33 4 78 92 70 00 Fax: 33 4 78 92 70 15 Email: biovision@ biovision.org Web: www.biovision.org
April 30-May 3 ACRP 2011 Conference & Expo Venue: Seattle, WA Web: www.acrp2011.com
MAY 2011 May 4-6 BioPartnering India Venue: Bangalore, India Web: www.techvision. com/bpi/
May 8-11
World Congress on Industrial Biotechnology and Bioprocessing Venue: Toronto, ON Tel: (202) 962-6630 Email: worldcongress@ bio.org Web: www.bio.org/ worldcongress
May 14-18 CALAS Annual Symposium Venue: Toronto, ON Tel: 416-593-0268 Fax: 416-593-9984
Email: office@ calas-acsal.org Web: www.calas-acsal.org
May 24-27
cspscanada.org Web: www. cspscanada.org
May 31-June 1
Canadian Society for Pharmaceutical Sciences Symposium Venue: Montreal, QC Tel: (780) 492-0950 Fax: (780) 492-0951 Email: bberekoff@
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March 27-31 ACS National Meeting & Exposition Venue: Anaheim, CA Tel: 202-872-6061 Email: nationalmeetings@acs. org Web: www.acs.org
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APRIL 2011 April 2 LMT Lab Day East Venue: New York, NY Tel: 203-459-2888 Fax: 203-459-2889 Email: info@LMTmag.com Web: www.lmtmag.com/lmtlabday/
April 6-8 ACETECH Symposium Venue: Whistler, BC Tel: (604) 683-5852 Fax: (604) 683-3879 Web: www.acetech.org
April 7-9 AMMI-CACMID Canada 2011 Annual Conference Venue: Montreal, QC Email: Matthew.Gilmour@ phac-aspc.gc.ca Web: www.cacmid.ca
April 11-12 Pharma Strategic Forum: New Alliances, Collaboration, and Open Innovation Venue: Toronto, ON Web: http://www. conferenceboard.ca/ conf/11-0070/agenda.aspx
April 13-14 5th Bioanalysis Workship Venue: Montreal, QC Tel: 514-236 4225 Email: contact@ canadianlcmsgroup.com Web: www.canadianlcmsgroup.com
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March 2011 Laboratory Focus
The 2011 Killam Research Fellowship winners announced The Canada Council for the Arts has named the winners of the 2011 Killam Research Fellowships. The Fellowships, among Canada’s most distinguished research awards, provide $70,000 a year for two years to each of the researchers enabling them to be released from teaching and administrative duties so that they can pursue independent research. A total of $1.12 million was awarded to eight projects, five of which are in the areas of chemistry and biology, the focus of their research will be in the areas of Alzheimer’s Disease, genetics, antibiotic resistance, inhibiting bacterial growth, music and solar fuels. Taking top honours in the sciences were Dr. Zongchao Jia, Queen’s University; professor’s Dolph Schluter and Chris Orvig, University of British Columbia; Warren Piers, University of Calgary and Gerard Wright, McMaster University. A well-published scientist, Dr. Jia has been recognized through many awards and research grants and his work is often cited by other research groups. Dr. Jia’s research will focus on the impact of a protein found within E. coli called AceK that could be targeted to inhibit bacterial growth in water and food sources. He will also examine the possibility of using AceK in the creation of biomolecules with reduced cost and CO2 emission. The Canada Research Chair for evolution and ecology at UBC, Professor Schluter is renowned in the area of evolutionary biology. He will undertake research with three-spined stickleback fish in the B.C. coastal lakes in order to understand the genetic changes that occur during evolution. He will also use this species, considered an ideal model for this type of research, to test how evolution occurs from the ecological to the genetic level. Professor Orvig’s work will focus on preclinical discovery and testing of novel compounds that will slow, halt or reverse the cognitive decline associated with Alzheimer’s disease. In 2009 he won both the Rio Tinto Alcan Award from the Canadian Society of Chemistry and the Bioinorganic Chemistry Award of the Royal Society of Chemistry; he was elected Fellow of the Royal Society of Chemistry in 2010. Warren Piers is a past recipient of national and international awards in chemistry; he has been elected a Fellow of the Royal Society of Canada and the Chemical Institute of Canada. He currently holds the S. Robert Blair Chair in Chemistry. His research project will focus on the catalytic splitting of water into green fuels hydrogen and oxygen using sunlight as the energy source. Recognized as one of the top scientists in this field, Dr. Wright, a full professor in biochemistry and biomedical sciences, is also the Director of the MG DeGroote Institute for Infectious Disease Research at McMaster. Dr. Wright’s research project includes two components: understanding antibiotic resistance and developing strategies to identify leads for new antibiotics from natural sources. Dr. Wright will also work to establish CARD: a complete antibiotic resistance database for use by researchers, scientists and clinicians. The recipients were chosen by the Killam selection committee, which included 14 eminent scientists and scholars representing a broad range of disciplines. Congratulations to all the winners!
Career Spotlight Bio-economy Career Profile Compiled by BioTalent Canada Position: Aquatic Ecologist Salary Range:$30,000 to $60,000 per year
What I do:
I work as an Aquatic Ecologist for Jacques Whitford. My role is to protect the water at the stream and lake levels, looking after fish, and ensuring the quality of their habitat. My day-to-day activities include protocol development for field sampling, data management and analysis, fieldwork, and report writing. My role includes working with freshwater ecology in Nova Scotia and other parts of the Maritimes. As an Aquatic Ecologist, I am a freshwater specialist for water ecosystems, while a Marine Biologist is a specialist who studies fish, mammals, and invertebrates in primarily saltwater locations. My company is hired by private contractors, developers, and the government to study the effects that various projects (including construction and development) may have on various lakes and streams. Through water quality and chemistry testing, and habitat characterization, I develop baselines that clients need to maintain throughout the life of the project and thereafter. As part of my reporting, I provide mitigation strategies to my clients, so that their projects do not have a negative influence on the established baselines whenever possible. My company also performs follow-up testing to ensure that a project continues to follow suggested guidelines.
What education and skills do candidates need for this position?
I have a Bachelor of Sciences in Biology with a minor in English. I then completed a Masters of Science, specializing in Aquatic Ecology. For individuals who have graduated recently, this tends to be a typical educational route for this type of position. Candidates should be detail oriented, observant, and organized. Above all, you need to be multidisciplinary in your approach to work. An Aquatic Ecologist needs to be strong in completing fieldwork, interpreting data, and report writing. You need to see the big picture and have common sense in your approach to the fieldwork and reporting to clients. It is important to have a common-sense approach and be down to earth. The fieldwork can be very challenging, physically and emotionally. It is important that you have perseverance, understand that the work is tough, and not complain about it. A job in ecology will never be a nine-to-five job, so you should be flexible to allow for the time and effort you will need to spend in the field during particular seasons.
What are the best parts of your job?
I appreciate the diversity of my position because the work involves field research, data management, and report writing. I also have the opportunity to see many beautiful places that other people may never see. But in the end, I enjoy the fact that I’m looking after the fish habitat and, through my work, I can educate people about its importance.
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