Laboratory Focus July 2013 by Promotive Communications

PHARMACEUTICAL

CLINICAL

CHEMICAL

FOOD

w w w. l a b o r a t o r y f o c u s . c a

High quality screening

of pharmacological chaperones for genetic diseases

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ENVIRONMENT

JULY 2013 Volume 17, Number 4

Using safe lock tubes

in mass spectrometry

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R&D News.......................... 1 Pharma Notes..................... 5 Appointments..................... 6 New Products................... 16 Calendar........................... 17 App Reviews...................... 18

RESEARCH SHOWS PROMISE FOR REDUCING GREENHOUSE GASES University of Calgary scientists are investigating how Alberta-grown biomass, such as straw and wood leftover from agricultural and forestry operations, could be used to clean up chemical contaminants in water from oilsands operations. “It’s important to look at areas of synergy for these industries,” says project lead David Layzell, a University of Calgary biological sciences professor affiliated with the Institute for Sustainable Energy, Environment and Economy. “We can get a bigger bang for the buck by getting our agriculture and forestry sectors to help the oil and gas sector solve some of its environmental problems.” Alberta’s oilsands mining industry currently uses about 123-millioncubic-metres of water annually that ends up in large tailings ponds. The organic compounds in this processed water are dominated by naphthenic acids, which are toxic and corrosive. In addition, microbes in the ponds convert these naphthenic acids to methane gas, which is emitted to the atmosphere. Methane is a greenhouse gas that has about 25 times more warming potential in Earth’s atmosphere than carbon dioxide. University of Calgary researchers are hoping to develop an activated biocarbon tailored for adsorbing these naphthenic acids thereby preventing the formation and release of methane greenhouse gasses.

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L to R: University of Calgary’s faculty researcher Josephine Hill, post-doctoral researcher Andrei Veksha and faculty researcher David Layzell. Photo by Mike Sturk.

The spent biocarbon could be used either as a source of renewable energy to displace fossil fuels, or land-filled as a permanent carbon storage, reducing greenhouse gas emissions. Layzell is currently collaborating with colleagues Josephine Hill, a chemical and petroleum engineer-

ing professor in the Schulich School of Engineering, and Andrei Veksha, a post-doctoral researcher at the Schulich School of Engineering who has expertise in making activated carbons. They have successfully made small amounts of biocarbon from aspen residues using “slow pyrolysis,” a relatively low-temperature process that ‘burns’ the biomass in the absence of oxygen. “We’re looking for a cheaper process with lower energy input to make the activated biochar. This would minimize the cost per cubic metre of using it to treat oilsands water, while also maximizing the greenhouse gas benefit,” Hill says. “Our preliminary results are promising.”

The team, which has held several meetings with industry experts, will need to show they can scale up their laboratory process and also do economic analysis to ensure their final products are cost-efficient for the oilsands industry. This research project received $57,500 from the Climate Change and Emissions Management Corporation (CCEMC), through the Biological Greenhouse Gas Management Program. The program is managed on behalf of CCEMC by Alberta Innovates Bio Solutions. To see this story online visit http://www.laboratoryfocus. ca/?p=1357

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NEWS ALLIANCE AIMS TO CREATE INTERNATIONAL SYSTEM The seven University of To- University of Toronto and the FOR SHARING GENOMIC DATA ronto-affiliated organizations Ontario Institute for Cancer Seven of Toronto’s leading research organizations have joined together in an unprecedented global alliance of more than 70 organizations engaging over 40 countries

around the world to set new unified standards for managing and sharing of genomic and clinical data enabling rapid progress in biomedical research.

participating in the alliance are the Samuel Lunenfeld Research Institute at Mount Sinai Hospital, Sunnybrook Health Sciences Centre, The Hospital for Sick Children (SickKids), University Health Network,

Research, which also serves as the Secretariat for the International Cancer Genome Consortium. “To realize personal, genomic-based treatments for Continued on page 3

PUBLISHER/EDITOR-IN-CHIEF Terri Pavelic STAFF WRITERS Shawn Lawrence Daniela Fisher INTERNS Anan Rahman Kayla Sippel CONTRIBUTING WRITERS CS Chanotiya GC Uniyal Meera Shanmuganathan Philip Britz-McKibbin Tom Arneman VS Pragadhessh

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July 2013

NEWS FEDERAL GOVERNMENT AND GENOME CANADA ACCELERATE GENOMICS DISCOVERY TO MARKET WITH GAPP

Minister of State (Science and Technology), Gary Goodyear (Left) discussing the technology behind Senator Kelvin Ogilvie’s first genetic sequencing machine Kelvin Ogilvie’s first genetic sequencing machine, also referred to as “gene-machine,” with David Pantalony, Curator, Physical Sciences and Medicine, Canada Science and Technology Museum. Photo Courtesy of Andrew Van Beek. Genome Canada has launched a new program designed to move genomics-based solutions from laboratories to the marketplace and increase collaboration between genomics scientists and those who use their research, such as industry and non-profit organizations. According to the Minister of State (Science and Technology) Gary Goodyear, advances in the field of genomics are essential. He believes the Genomic Applications Partnership Program (GAPP) will encourage advances by stimulating investment from private and public partners to fund future projects. “Genomics science is at the Continued from page 2

core of the economic activity of life sciences research. More than ever before, the field of genomics is equipping Canadian businesses with cutting-edge science and technologies that are not only helping to address challenges we face, but are also driving economic growth and creating high quality jobs,” he said. By way of Genome Canada, the federal government will commit $30 million to the program. Through regional Genome Centres, it will leverage additional funding from partners and industry to collect a total of $90 million dedicated to domestic genomics research and development. According to Dr. Pierre Meulien, disease, we must pool expertise and break down institutional barriers,” says Dr. Catharine Whiteside, dean of the University of Toronto Faculty of Medicine and vice provost, Relations with Health Care Institutions. “By integrating U of T’s thriving community of researchers, teachers and clinicians, this alliance will have a powerful impact on health locally and globally.” The past decade has brought about an explosion of genomic data in medical research. But currently much of this data is collected and analyzed in isolation – by disease, by country, or by institution – limiting its impact. The alliance aims to bring together ethics, privacy, medicine, research and technology to set new, unified standards that will allow data across the world to be shared in a responsible, ethical manner. This will help

president and CEO of Genome Canada, it is expected that early-stage products, tools and processes will emerge from the new program. “The program was designed based on extensive consultation both with the genomics research community and the community of users of genomics research to ensure it was meeting clearly defined needs,” he said. Minister Goodyear also announced renewed funding of $29 million for five genomics research facilities across Canada, as determined by the operational reviews of an International Review Committee. The Science and Technology Innovation Centres is providing access to genomic, proteomic, metabolomic and bioinformatics technologies to Genome Canada-funded projects, as well as those of the greater community. The Centres also offer advice on research study design and appropriate technologies required to carry out research proposals. The Economic Action Plan 2012 has provided $60 million for the launch of the GAPP program and the sustaining of the Science and Technology Centres until 2014 to 2015. Of that amount, $26 million will go to the GAPP, $29 million will renew the operations of the five Centres, and $5 million will support Canadian leadership on two international consortia, the Structural Genomics Consortium and International Barcode of Life Consortium. Another $4 million will be drawn from Genome Canada’s budget and allocated to the GAPP.

THINKING OUTSIDE THE PROSTATE CANCER BOX: TARGETING THE N-TERMINAL

researchers worldwide collaborate to tackle more complex problems with more efficiency. “International cooperation is essential to make personal medicine a reality,” says Dr. Stephen Scherer, director of the University of Toronto’s McLaughlin Centre and The Centre for Applied Genomics at SickKids. “The alliance will create a robust framework, enabling scientists to collaborate and bring treatments to patients sooner.” The new alliance also includes the U.S. National Institutes of Health, the Wellcome Trust Sanger Institute in the U.K. and the Beijing Genomics Institute in China among its members.

Research published in the Journal of Clinical Investigation suggests that a new drug developed by the BC Cancer Agency has the potential to succeed in ways that conventional prostate cancer drugs cannot. Dr. Marianne Sadar, a distinguished scientist at the BC Cancer Agency, and Dr. Raymond Anderson, a distinguished professor at the University of BC, developed EPI-001 and have provided proof-of-principle that the drug works on prostate cancer cells currently resistant to drug therapies. To develop EPI-001, Dr. Sadar’s team focused on the N-terminal, an area at the opposite end of the protein structure, rather than the traditionally targeted androgen receptor protein. The “engine,” as Dr. Sadar calls it. EPI-001 could be a very significant drug discovery. Current drug therapies for advanced prostate cancer aim at the opposite end of the hormone receptor, away from the “engine.” These drugs effectively slow tumour growth; however they do not cure the patient of the disease. On average, in 20 per cent of patients the prostate cancer will recur. Also, at this time there are no other successful treatment options. “The approach that Dr. Sadar has taken is novel, and has the potential to overcome treatment-resistant prostate cancer,” said Dr. Kim Chi, medical director, clinical trials unit at the BC Cancer Agency. “I’m really excited about the potential of this drug and look forward to getting it into clinical trials here at the BC Cancer Agency, so that it can benefit patients.” Members of the international medical community are also taking notice of EPI-001. Dr. Oliver Sartor, medical director at the Tulane Cancer Center in New Orleans, expressed his interest in the drug’s pre-clinical results. “These compounds need to enter clinical trials to determine whether the promising activity in model systems can be replicated in the human setting,” said Sartor.

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NEWS

OCE AND OBI INVEST $400,000 TO BACK NEUROSCIENCE ENTREPRENEURS Ontario Centres of Excellence (OCE) and the Ontario Brain Institute (OBI) are co-investing $400,000 to turn Ontario-based neuroscience researchers into ‘neuro-entrepreneurs’ and their work into viable companies. Jointly funded through the OCE-OBI Entrepreneurship Fellowship program, eight postgraduate (M.Sc., PhD and postdoctoral fellows) and early stage entrepreneurs are receiving one year awards of $50,000 each to support the commercialization of discoveries that help diagnose, treat or cure brain disorders. In addition to funds, the entrepreneurs will also receive

mentoring, training and opportunities to receive follow-on funding. They will work full-time with the OBI and its partners from across Ontario on commercialization activities related to their neurotechnology ideas.

INVESTMENT OF MORE THAN $3 MILLION TO SUPPORT RESEARCH FACILITY AT MEMORIAL UNIVERSITY To support research and identify new ways to optimize oil recovery, the Research & Development Corporation of Newfoundland and Labrador (RDC) and the Hibernia Management and Development Company Ltd. (HDMC) are investing $1.635- and $1.7-million respectively for the creation of a state-of-the-art enhanced oil recovery research facility at Memorial University’s St. John’s campus. “Investing in research to maximize the potential of resources in our offshore will have direct economic benefits for Newfoundland and Labrador,” said Keith Hutchings, minister responsible for the Research & Development Corporation. “Our province’s academic community and oil and gas leaders are researching new technologies to extract additional resources from current and future oil fields. Collaboration between government, industry and academia will continue to support an environment that enhances the competitive advantage of our province.” Research efforts in the new laboratory will focus on enhanced oil recovery, which is utilized to increase the amount of crude oil extracted from an oil field and extend

the field life. Funding from RDC and HMDC will advance research and development (R&D) capacity at Memorial. “Building new research labs and facilities is critical to expanding our R&D capacity, and strengthening our long-term economic performance and global competitiveness. Applied EOR research represents a strategic investment that is critical to sustaining economic prosperity in Newfoundland and Labrador,” said Glenn Janes, CEO, RDC. The investment from HMDC is in addition to its investment of more than $11 million to fund the purchase of laboratory equipment and research into enhanced oil recovery announced in December 2012. Dr. Lesley James, an assistant professor of process engineering and the Chevron Chair in Petroleum Engineering in the Faculty of Engineering and Applied Science at Memorial University, is the principal investigator of the new laboratory. Her research expertise centres on the recovery of oil and gas offshore Newfoundland and Labrador. To see this story online visit http://www.laboratoryfocus. ca/?p=1368

The eight recipients are: • Hisham Alshaer; Toronto Rehabilitation Institute, University Health Network; ApneaDx Inc.; Sleep apnea home diagnosis device. • Amir Manbachi; University of Toronto; Spinesonics Medical Inc.; Device that allows visualization of screw positioning during insertion into the spine. • Joost Schulte; Hospital for Sick Children; Oxalys Pharma; Therapeutics for Huntington’s disease. • Peter Siegler; Ryerson University; Device that detects bending and spatial positioning of biopsy needles

during insertion into the brain. • Bardia Bina; University of Toronto; Augmented reality display system for use in surgical procedures. • Jack Lee; Movement Disorders Center; MDDT; Device for characterizing tremors allowing doctors to accurately identify the optimal antitremor drug injection site. • Abraham Heifets; University of Toronto; Chematria, Inc.; Software for predicting molecules that will have a greater chance of becoming successful drugs. • Natasha D’Souza; Carleton University; VirtualEyeSee; Virtual therapy system for children with autism. To see this story online visit http://www.laboratoryfocus. ca/?p=1366

STEM CELL THERAPEUTICS’ CLINICAL ADVISOR AND COLLABORATOR RECEIVES PRESTIGIOUS NATIONAL AWARD

Drs. Steven Narod (L) and Aaron Schimmer, Ontario-based recipients of this year’s Canadian Cancer Society Awards for Excellence in Cancer Research. (CNW Group/Canadian Cancer Society [Ontario Division]). Dr. Aaron Schimmer has been awarded a prestigious national award for his groundbreaking cancer research for the second time in approximately a year. Each year, the Canadian Cancer Society honours four exceptional Canadian scientists who have made significant contributions to progress in cancer research. This year, Dr. Schimmer is the recipient of the Bernard and Francine Dorval Prize, which is awarded to a promising investigator who began their independent research within the previous 10 years and who has made outstanding contributions to basic biomedical research. In 2012, Dr. Schimmer received the Till & McCulloch Award, presented each year by the Stem Cell Network in recognition of the year’s most influential

peer-reviewed article by a researcher in Canada. Dr. Schimmer’s laboratory is investigating the repurposing of several FDA-approved drugs with favourable pharmacokinetic and toxicological properties for use as novel anticancer agents. One of these drugs is tigecycline, a broad-spectrum antibiotic. Stem Cell Therapeutics recently acquired exclusive worldwide rights to an innovative clinical cancer stem cell program based on Dr. Schimmer’s discovery that tigecycline targets and kills leukemia cells and leukemic stem cells. The company also appointed him to its scientific advisory board. To see this story online visit http://www.laboratoryfocus. ca/?p=1371

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Laboratory Focus July 2013

PHARMA NOTES Contract development and manufacturing company Therapure Biopharma Inc. (Mississauga, ON) will participate as a subcontractor for DynPort Vaccine Company LLC (Frederick, MD) to support the development of a prophylactic countermeasure to prevent the effects of organophosphorus nerve agent poisoning. DynPort was awarded the contract by the U.S. Department of Defense. Therapure’s sub contract under the above prime contract includes process optimization as well as manufacture of all clinical and nonclinical materials (drug product) to support DVC’s contract to develop, test and obtain the US Food and Drug Administration (FDA) approval for human plasma derived butyrylcholinesterase (HuBChE), a blood plasma protein that binds and inactivates nerve agents. Xenon Pharmaceuticals Inc. (Vancouver, BC) has exercised its option to an exclusive worldwide license to XEN701, an antisense drug discovered in collaboration with Isis Pharmaceuticals (Carlsbad, CA). For the license of XEN701, Isis earns a $2 million payment from Xenon. XEN701 is designed to inhibit the production of hepcidin, a target Xenon identified utilizing its extreme genetics platform for the treatment of anemia of chronic disorders (ACD). XEN701 is currently being evaluated in studies to support clinical development. Xenon plans to initially develop XEN701 for patients with chronic kidney disease who are intolerant of or who are poor responders to erythropoietin (Epo) therapy. XEN701 is the first drug to enter development from Xenon’s collaboration with Isis Pharmaceuticals Inc. Zenith Epigenetics Corp. (Calgary, AB) has commenced operations as an early stage research company. Zenith was formed as a result of a plan of arrangement involving Resverlogix Corp., RVX Therapeutics Inc. and Zenith. The management team of Zenith

will be led by the management team of Resverlogix, including Donald McCaffrey as president and CEO, Brad Cann as CFO, Kenneth Lebioda as senior VP Business & Corporate Development, Dr. Norman Wong, as CSO and chairman of the Scientific Advisory Board, Dr. Jan Johansson, as senior VP Medical Affairs, Dr. Gregory Wagner, as senior VP Research and Development and Dr. Allan Gordon, as senior VP Clinical Development. The board of directors of Zenith consists of Dr. Peter Johann, Donald McCaffrey, Kenneth Zuerblis, Dr. Eldon Smith, Kelly McNeill and Arthur J. Higgins. Medicago Inc. (Québec, QC) has received clearance by Health Canada to initiate its Phase 2 dose-sparing clinical trial for a H5N1 Avian Influenza VLP vaccine candidate. All clinical lots have been produced and the trial will commence with interim results expected in the summer of 2013. To date, three clinical trials have been performed on a total of 403 subjects. Medicago’s H5N1 vaccine candidate was found to be safe and well tolerated and induced a solid immune response in a U.S. Phase 1 study that was recently completed using a 20 µg dose of the H5 VLP vaccine with or without the Alhydrogel® (alum adjuvant) or the glucopyranosyl Lipid A (GLA-AF) adjuvant, given

either intradermally (ID) or intramuscularly (IM). The results obtained revealed that all formulations were safe and well-tolerated and both alum and GLA induced antibody levels met the three CHMP criteria for licensure of influenza vaccines. The Phase 2 dose-sparing study is designed as a multi center, observer blind, placebocontrolled study using the IM route of administration, with alum or GLA-based adjuvant in healthy adults 18 to 60 years of age. A total of 390 subjects will be randomized to receive two doses of the H5 VLP vaccine formulated with alum adjuvant or GLA-SE adjuvant or placebo. The primary endpoints are immunogenicity evaluated 21 days after each administration as well as safety and tolerability after each administration and 12 months after the last injection. As a secondary endpoint, the immunogenicity and crossreactive antibodies induced by the H5 VLP vaccine will be evaluated. The trial is anticipated to take 15 months to complete with initial safety and immunology data expected during the summer of 2013. Transition Therapeutics Inc. (Toronto, ON) announces that Eli Lilly and Company (Lilly) has exercised its option to assume all development and commercialization rights to type 2 diabetes drug candidate TT-401. In

conjunction with this assumption of rights, Transition will receive a US$7 million milestone payment. Lilly and Transition have amended their agreement to address future development of TT-401 and associated financial arrangements. Lilly will assume all costs and perform all future development and commercialization activities of TT-401. Transition will contribute payment of US$14 million to Lilly in three separate installments during the Phase 2 clinical study. If TT-401 is successfully commercialized, Transition will be eligible to receive approximately US$240 million in additional milestone payments. Transition will also be eligible to receive a double-digit royalty on sales of TT-401 products and a low single digit royalty on related compounds. BELLUS Health Inc. (Laval, QC) has agreed to acquire Thallion Pharmaceuticals Inc. (Dorval , QC) for approximately $6.332 million. Thallion is developing Shigamabs®, a monoclonal antibody therapy being evaluated for the treatment of Shiga toxin-producing E. coli (STEC) bacterial infections. STEC infections can lead to hemolytic uremic syndrome (HUS), a condition principally affecting the kidneys that often leads to dialysis and in certain cases death. BELLUS Health’s lead program is KIACTA™,

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a drug candidate currently in a Phase 3 confirmatory study for the treatment of AA amyloidosis, a rare disease resulting in kidney dysfunction that often rapidly leads to dialysis and death. Following Health Canada approval, TauRx Therapeutics Ltd. (Aberdeen, UK) and Toronto Memory Program (Toronto, ON) have jointly announced the Canadian launch of a group of Phase 3 clinical trials for TauRx Therapeutics’ LMTX™, the company’s investigational treatment aimed at slowing or halting the progression of mild to moderate Alzheimer’s disease. The Toronto Memory Program is the first of at least five medical centres in Canada that will carry out the Phase 3 Alzheimer’s trials. TauRx’s clinical trials for mild to moderate Alzheimer’s and for behavioral variant Frontotemporal Dementia, a rare neurodegenerative disease caused by a similar form of pathology as in Alzheimer’s, are the first Phase 3 trials of a Tau Aggregation Inhibitor (TAI), which targets and dissolves ‘tau tangles’ in the brain, and is directly linked to the development of the disease. If successful, LMTX™ will be the first tau-based treatment approach for Alzheimer’s disease. The TauRx Phase 3 study program will involve over 1,700 patients in more than 20 countries.

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APPOINTMENTS

Egenix, Inc. announces the appointment of Arshad Siddiqui to its board of directors. Prior to this, he was an associate director of antiviral chemistry at Shire BioChem Pharma where he was responsible for the development of several clinical candidates in the areas of HIV, HBV and HCV. Dr. Siddiqui relocated to NeoGenesis Pharmaceuticals, as a senior director of medicinal chemistry. He was also director of medical chemistry at Schering Plough and Merck in Cambridge, MA. Dr. Siddiqui’s careers span over 22 years, and includes contributions to discovery of Epivir and multiple clinical stage compounds. Dr. Siddiqui is a co-recipient of Prix-Galien, Canada (1996) and has published over 61 research articles and over 68 patents. He received his Ph.D. in chemistry from the University of Waterloo. Qu Biologics Inc. (Vancouver, BC) has added Robert Pelzer to its board of directors. Pelzer was most recently president of Novartis Corporation. In that capacity, Pelzer was responsible for the Novartis Group Companies in the U.S. Previously, Pelzer served as global general counsel and head of Legal Services at Novartis Pharma AG, based in Basel, Switzerland. Prior to joining Novartis in 2002, Pelzer served as general counsel and senior vice president at DuPont Pharmaceuticals. Pelzer has held a number of directorships including with the Pharmaceutical Research and Manufacturers of America industry association, as well as with numerous Novartis subsidiaries, Idenix Pharmaceuticals and Litebook Company. MEI Pharma, Inc. announces the appointment of Dr. Nick Glover to its board of directors. Dr. Glover was most recently president and CEO of YM BioSciences, an oncology drug development company acquired by Gilead Sciences for $510 million in February 2013. The appointment of Dr. Glover increases MEI Pharma’s board to seven members, including six independent directors. Prior to his role with YM, Dr. Glover was president and CEO of Viventia Biotech and was also an investment manager at MDS Capital, a life sciences venture capital firm. Dr. Glover holds a B.Sc. (Hons) in Chemistry from the University of East Anglia, U.K., and

a Ph.D. in Chemistry from Simon Fraser University, Canada. Genome Prairie has named Michael Reimer as its director of business development. In this role, Reimer will work towards enhancing the organization’s partnership objectives between industry and public research institutions. Reimer’s background reflects a growing breadth of experience in technical and management positions within Manitoba’s ag-biotech cluster. He completed his M.Sc. in Human Nutritional Sciences from the University of Manitoba in 2007 and subsequently joined the Canadian International Grains Institute as a technical specialist. In 2012, he joined the Manitoba Pulse Growers’ Association as the acting executive director. Based in Winnipeg, Reimer will work with stakeholders from across Manitoba and Saskatchewan to build and strengthen Genome Prairie’s collaborative relationships. Dr. Terrance P. Snutch has been appointed to the Governing Council of the Canadian Institutes of Health Research (CIHR) for a three-year term. Dr. Snutch is internationally renowned for his contributions in the field of neuroscience. He is a professor and Canada Research Chair in the Michael Smith Laboratories, Departments of Psychiatry and Zoology, and the Brain Research Centre at the University of British Columbia. His many scientific contributions include the development of novel methodology to clone genes from the brain resulting in the isolation of the first serotonin neurotransmitter receptor and major ion channels involved in conducting brain electrical signals. His many awards include Howard Hughes Medical Institute International Research Scholar, the Medical Research Council of Canada Scientist, and the Canadian Institutes of Health Research Senior Scientist. Dr. Snutch has also been inducted as a Fellow of both the Royal Society of Canada and the Canadian Academy of Health Sciences. Dr. Bob Kiaii has been appointed as the inaugural Ray and Margaret Elliott Chair in Surgical Innovation in the Department of Surgery, Schulich School of Medicine & Dentistry, Western Univer-

sity, for the period July 1, 2013 to June 30, 2018. The Ray and Margaret Elliott Chair in Surgical Innovation was founded in 2011 by an extraordinary gift of $1.5M from the Elliott family which was matched with funds from Western University. As the Ray and Margaret Elliott Chair, Dr. Kiaii’s role will include building teams in advancing technology changes in surgery; contributing to the advancement of simulation and simulation-based training at Western; participating in the establishment of the Biomedical Devices Institute in London; and in fostering relationships with the medical device industry. Dr. Kiaii graduated with a Bachelor of Science in Biochemistry from the University of British Columbia. He completed his MD at Schulich Medicine & Dentistry, Western University followed by General Surgery residency training at the University of Calgary and a Cardiac Surgery residency at Western. He subsequently completed a fellowship in Cardiac Transplantation at Western and a second fellowship at the Leipzig Heart Centre in Minimally Invasive and Robotic Cardiac Surgery in Germany. Dr. Kiaii also presently serves as the Director of the Minimally Invasive Robotic Cardiac Surgery Program at LHSC. In addition Dr. Kiaii is an internationally acclaimed clinician and researcher in minimally invasive cardiac surgery. Helix BioPharma Corp. announces the appointment of Stace Wills to its board of directors. Wills is a resident Canadian and his appointment was effective June 12, 2013. Helix also announced that Andrew J. MacDougall, who had agreed to serve on the board of directors on an interim basis pending the appointment of a resident Canadian director voluntarily resigned as a director following the appointment. The board is comprised of six directors, five of whom are independent of Helix. Wills is currently vice-president, Company Creation, with Innovate Calgarys’s Company Creation program. Prior to Innovate Calgary, Wills served as director of corporate development for Elluminate Inc., a Calgary based e-learning software company that was sold to NASDAQlisted Blackboard Inc. in 2010. He also served in senior positions with ag-biotech company Alta Genetics

Inc., and co-founded venture capital organization Accolade Capital Inc. He holds a Bachelor of Commerce degree from the University of Calgary, and has a Canadian Investment Manager (CIM) designation. The Canadian Institutes of Health Research (CIHR) announces the appointment of Dr. Stephen Robbins as scientific director of CIHR’s Institute of Cancer Research, effective July 1, 2013. Dr. Robbins is an associate professor in the Departments of Oncology, Biochemistry and Molecular Biology at

the University of Calgary. He is also director of the Southern Alberta Cancer Research Institute. Currently, Dr. Robbins is a scientist at Alberta Innovates Health Solutions and associate director of research for Alberta Health Services Cancer Care. Along with winning several awards and distinctions for his teaching, Dr. Robbins has served on and chaired several national grant panels including the National Cancer Institute of Canada, Cancer Research Society and the CIHR. John Jacobson has been appointed Deputy Minister of the Ministry of Technology, Innovation and Citizens’ Services. The announcement was made in conjunction with the swearing in of the new provincial cabinet in Victoria, BC. Jacobson will serve as Deputy Minister to the Hon. Andrew Wilkinson, Minister of Technology, Innovation and Citizens’ Services. BC Innovation Council is part of this new ministry. Prior to his appointment, Jacobson was president and CEO of BCIC.

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Laboratory Focus July 2013

High quality screening of pharmacological chaperones for genetic diseases:

Rescuing mutant enzymes from degradation?

BY: MEERA SHANMUGANATHAN AND PHILIP BRITZ-MCKIBBIN, DEPARTMENT OF CHEMISTRY AND CHEMICAL BIOLOGY, MCMASTER UNIVERSITY

Expanded newborn screening: New therapies for treatment of genetic diseases The advent of multiplexed tandem mass spectrometry (MS/MS) technology has led to expanded newborn screening (NBS) programs for pre-symptomatic diagnosis of rare yet treatable genetic disorders.1 Although the diagnostic performance of MS/MS-based assays is important for inclusion of fatal or debilitating diseases within provincial neonatal screening panels2, effective treatment options remain crucial for reducing mortality and clinically significant morbidity among children.3 For instance, early detection of phenylketonuria (PKU) by MS/MS allows for timely intervention based on a Lphenylalanine restricted diet and/or tetrahydrobiopterin supplementation to prevent irreversible neurological impairment.4 However, the lack of dietary and/or pharmaceutical strategies for treatment of other inherited disorders presents ethical issues to NBS without tangible benefits to patient care or healthcare savings. Lysosomal storage disorders (LSDs) are a class of in-born errors of metabolism that result in protein deficiency, where mutant enzymes have low residual catalytic activity for glycolipid substrates in the lysosome. Gaucher disease (GD) represents the most common form of LSD that is associated with clinically relevant mutations of b-glucocerebrosidase (GCase).5 Currently, either using a recombinant enzyme or using recombinant enzymes are the main therapies for treatment of GD and related LSDs; however these are limited by high costs, biweekly intra-venous injections, adverse allergic reactions and/ or poor efficacy when treating severe disease phenotypes associated with neurological symptoms in the case of type II/III GD patients.6 Alternatively, enzyme enhancement therapy based on small molecules that can restore the function of mutant enzymes represents a promising therapeutic option for treatment of diseases associated with protein misfolding.7 Due to stringent dietary management practices that may lead to poor adherence, nutritional deficiencies and/or variable clinical outcomes, there is

FEATURE

growing interest in developing oralbased drug therapies that address the underlying causes of protein deficiency.

Pharmacological chaperones: Inhibitors as enzyme enhancers? Pharmacological chaperones (PCs) are small extrinsic molecules that stabilize and promote folding of mutant protein in order to evade endoplasmic-recticulum-associated degradation.8 Despite the early use of high dose vitamin/cofactor therapy for treatment of mild PKU9, the first report of PCs as novel therapeutic agents for genetic disorders consisted of competitive drug inhibitors that increased protein conformational stability upon reversible binding.10 However, substrate-based mimics represent paradoxical therapeutic agents for enzyme enhancement therapy since inhibitors attenuate catalytic activity that is needed for relief of deleterious substrate accumulation.11 To date, high throughput drug screening has relied on fluorescencebased inhibition assays for lead candidate selection from large chemical libraries with confirmatory testing based on thermal stability and/or patient-derived cell-based assays.12 For these reasons, major drug patents of PCs for treatment of GD have largely consisted of potent reversible inhibitors of GCase.13 The lack of efficacy reported in preliminary clinical trials of Isofagomine (IFG) for treatment of adult type 1 GD patients has dampened enthusiasm of PCs for enzyme enhancement therapy. Although the poor bioavailability and cell uptake of IFG has been implicated in its lower biological activity in vivo, the high attrition rate of PCs likely stem from the inherent bias of screens based on enzyme inhibition. For instance, ambroxol (ABX) is a mixed-type inhibitor of GCase that was first discovered using a thermal stability assay as a primary screen despite its weak inhibitory potency.14 In this context, we have developed an alternative assay for functional screening of PCs that directly measures the chaperone potency of small molecules for unfolded/inactive enzymes when using capillary electrophoresis (CE).

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FEATURE

CE offers a versatile micro-separation format for drug screening due to its short analysis times, low reagent costs, minimal sample requirements and high selectivity that reduces spectral interferences, including stereoisomers and complex natural product extracts.15 Cerezyme® (imiglucerase) is a modified recombinant GCase that catalyzes the hydrolysis of the fluorogenic substrate, methylumbelliferyl-βD-glucopyranoside (MUG) to generate two products, namely 4-methylumbelliferone (MU) and D-glucose, as shown in Figure 1. The activity of GCase correlates with the rate of product formation (MU), where resolution of substrate, product and internal standard is achieved by CE within four minutes. Recently, we introduced restoration of enzyme activity upon denaturation (READ) as a new approach for functional screening of drug candidates based on their chaperone activity unlike conventional inhibition screens.16 In this case, READ assesses the dose-dependent potency of ligands to restore the activity of unfolded and/or inactive enzymes as a surrogate for mutant protein. Briefly, GCase is first exposed to increasing urea as a solubilizing denaturant to perturb the equilibrium distribution of folded protein conformers prior to addition of ligand (PC) and then substrate (MUG) to initiate the enzyme reaction for a fixed time period followed by thermal quenching.16 Figure 1 shows a series of electropherograms reflecting the impact of PC binding on modulating apparent GCase activity under neutral pH conditions when using 0 M (folded/

PCs not only represent novel therapeutic agents on their own merit, but also useful adjuvants in enzyme replacement therapy and stabilizers for recombinant protein to enhance their long-term biological activity.

Figure 1 MUG

MU OH OH

GCase McIIvane buffer 10mM Taurocholate O

MUG

+ O

apo-GCase holo-GCase-DTZ (+ 60 µM)

Absorbance (mAu)

Screening for chaperone activity: Restoration of enzyme activity upon denaturation

PC as stabilizer EOF

(b) 4M urea

PC as inhibitor 20 (a) 0M urea 0 0.5

1.0

1.5

2.0 2.5 Time (min)

3.0

3.5

4.0

Series of electropherograms highlighting the resolution of product (MU) from substrate (MUG) and internal standard (IS), where enzymecatalyzed reactions were performed using GCase under native (0 M urea) and denaturing (4 M urea) conditions. The addition of diltiazem (DTZ) highlights the paradoxical properties of inhibitors as stabilizers of misfolded/unfolded enzymes, where DTZ acts as a weak mixed-type inhibitor (IC50 ≈ 60 mM, pH 7.2) under native conditions, which serving as a significant stabilizer of GCase that is largely inactivated at 4 M urea without ligand (apo-GCase).16

active) and 4 M urea (unfolded/inactive).16 Diltiazem (DTZ) is a previously approved FDA drug that serves as a Ca2+ channel blocker for treatment of hypertension and recently shown to function as a mixed-type inhibitor of GCase.17 As expected, 60 μM DTZ acts as a weak inhibitor of folded GCase at 0 M urea (Half maximal inhibitory concentration (IC50) = 56 mM, pH 7.2), however it also functions as a stabilizer of GCase regaining about 30 per cent of residual activity at 4 M urea that is nearly fully abolished for ligand-free apo-GCase as shown in Figure 1. In contrast, the potent competitive inhibitor of GCase, IFG (IC50 = 4.6 nM, pH 7.2) significantly reduces product turn-over at 50 nM under native conditions, while restoring about 50 per cent of normalized GCase activity at 4 M urea.16 Nonetheless, the absolute activity of GCase is still lower due to the much stronger inhibitory potency of IFG relative to DTZ.16 Although there is a general correlation between inhibitory potency and chaperone activity, there are many exceptions notably among mixed-type inhibitors that bind to different allosteric sites on protein.14 Indeed, READ demonstrates that DTZ possesses greater

chaperone activity for GCase relative to ABX despite their similar inhibitory potency.16 Figure 2 shows an overlay of three inactivation curves for GCase as a function of urea and DTZ dosage, including the ligandfree apo-GCase enzyme. A shift in the mid-point for urea inactivation reflects increased thermodynamic stabilization of protein upon ligand binding with a concomitant enhancement in residual GCase activity under denaturing conditions. Notably, this approach reduces false-negatives derived from inhibitor screens since ligand interactions that do not inhibit native GCase can still contribute to protein stabilization with higher catalytic activity even when the ligand-free enzyme is irreversibly denatured.16 In all cases, measured enzyme activities were normalized to 0 M urea conditions at a specific ligand dosage in order to better compare the chaperone potency of PCs that have widely different binding affinities and modes of interaction(s) with specific enzymes.16

Future outlook PCs represent a promising therapeutic approach to rescue protein misfolding that has been applied primar-

ily to enzymes associated with LSDs with growing interest to other classes of genetic diseases that lack effective treatment options for severe phenotypes, such as cystic fibrosis and phenylketonuria. Although preliminary results of IFG have yet to demonstrate adequate clinical efficacy, inhibition screens may represent a major source of late-stage drug attrition since inhibitor potency is only an approximate indicator of chaperone activity. Although most primary screens use the wild-type/folded enzyme for drug candidate selection, they often have varied efficacy when applied to different mutant enzymes of clinical relevance. Future work will adopt READ to a fluorescence-based microarray format to enable high quality in vitro screening of FDA-approved drug libraries as a way to “fast-track” safe yet affordable clinical therapies to patients with rare genetic diseases. PCs not only represent novel therapeutic agents on their own merit, but also useful adjuvants in enzyme replacement therapy and stabilizers for recombinant protein to enhance their long-term biological activity.

References 1. Chalcraft KR, Britz-McKibbin P.

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Figure 2

Restored enzyme activity

GCase GCase-DTZ (60 µM) GCase-DTZ (600 µM)

1.0

Normalized enzyme activity

Gaucher disease. J. Biol. Chem. 2009, 284: 23502-23516. 15. Shanmuganathan, M. Britz-McKibbin P. High quality screening of drugs by capillary electrophoresis: A review. Anal. Chim. Acta 2013, 773: 24-36. 16. Shanmuganathan M, Britz-McKibbin P. Functional screening of pharmacological chaperones via restoration of enzyme activity upon denaturation. Biochemistry 2012, 51: 7651-7653. 17. Shanmuganathan M, Britz-McKibbin P. Inhibitor screening of pharmacological chaperones for lysosomal β-glucocerebrosidase by capillary electrophoresis. Anal. Bioanal. Chem. 2011, 399: 2843-2853.

0.8 O

0.6

NH +

O O

N S

0.4 0.2

Increased stabilization

0.0 0

Meera Shanmuganathan and Philip Britz-McKibbin are researchers in the Department of Chemistry and Chemical Biology, McMaster University.

[Urea ] (M) Dose-dependent enzyme inactivation curves for functional screening of PCs for GCase, which shows the increase in stabilization conferred by reversible binding to the mixed-type inhibitor, diltiazam (DTZ) that results in a recovery of enzyme activity upon denaturation conditions (4 M urea). 16

Newborn screening of inborn errors of metabolism by capillary electrophoresis-electrospray ionization-mass spectrometry: a second-tier method with improved specificity and sensitivity. Anal. Chem. 2009, 81: 307-14. Gelb MH, Turecek F, Scott CR, Chamoles NA. Direct multiplex assay of enzymes in dried blood spots by tandem mass spectrometry for the newborn screening of lysosomal storage disorders. J. Inherit. Metab. Dis. 2006, 29: 397-404. Wilcken B, Haas M, Joy P, Wiley V, Bowling F, Carpenter K, Christodoulou J, Cowley D, Ellaway C, Fletcher J, Kirk EP, Lewis B, McGill J, Peters H, Pitt J, Ranieri E, Yaplito-Lee J, Boneh A. Expanded newborn screening: outcome in screened and unscreened patients at age 6 years. Pediatrics 2009, 124: e241-e248. Berry SA, Brown C, Grant M, Greene CL, Jurecki E, Koch J, Moseley K, Suter R, van Calcar SC, Wiles J, Cederbaum S. Newborn screening 50 years later: access issues faced by adults with PKU. Genet. Med. 2013, doi: 10.1038/gim.2013.10. Rosenbloom BE, Weinreb NJ. Gaucher disease: a comprehensive review. Crit. Rev. Oncog. 2013, 18: 163-75. Deegan PB, Cox TM. Imiglucerase in the treatment of Gaucher disease: a history and perspective. Drug Des. Devel. Ther. 2012, 6: 81-106.

7. Desnick RJ. Enzyme replacement and enhancement therapies for lysosomal diseases. J Inherit. Metab. Dis. 2004, 27: 385-410. 8. Brooks DA. Getting into the fold. Nature Chem. Biol. 2007, 3: 84-85. 9. Muntau AC, Röschinger W, Habich M, Demmelmair H, Hoffmann B, Sommerhoff CP, Roscher AA. Tetrahydrobiopterin as an alternative treatment for mild phenylketonuria. N. Engl. J. Med. 2002, 347: 2122-32. 10. Fan JQ, Ishii S, Asano N, Suzuki Y. Accelerated transport and maturation oflysosomal alphagalactosidase A in Fabry lymphoblasts by an enzyme inhibitor. Nat. Med. 1999, 5: 112-15. 11. Fan JQ. A contradictory treatment for lysosomal storage disorders: Inhibitors enhance mutant enzyme activity. Trends Pharmacol. Sci. 2003, 24: 355-360. 12. Steet RA, Chung S, Wustman B, Powe A, Do H, Kornfeld SA. The iminosugar isofagomine increases the activity of N370S mutant acid beta-glucosidase in Gaucher fibroblasts by several mechanisms. Proc. Natl. Acad. Sci. U.S.A. 2006, 103: 13813-13818. 13. Benito JM, García Fernández JM, Ortiz Mellet C. Pharmacological chaperone therapy for Gaucher disease: a patent review. Expert Opin. Ther. Pat. 2011, 21: 885903. 14. Maegawa GH, Tropak MB, Buttner JD, Rigat BA, Fuller M, Pandit D, Tang L, Kornhaber GJ,

Hamuro Y, Clarke JT, Mahuran DJ. Identification and characterization of ambroxol as an enzyme enhancement agent for

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B Y: C S CHA NOTIYA , VS P RA G ADHESSH, G C U NIYAL C SIR - CENTRA L INS TITUTE OF MED ICINA L A ND A ROMATIC P L ANTS, L U CKNOW - 226 015, INDIA

Avoiding interferences and contaminants using safe-lock tubes in mass spectrometry studies of natural products Abstract Plasticwares require the inclusion improved [M+H]+ detection. On the ric studies. Moreover, mass spectroof several chemicals to enhance contrary, tubes from other manufac- metric analysis of biological materitheir stability, durability and perforturers have shown leaching effects. als on polluted polymer tubes from APPLICATION NOTE No. 282 I Page 3the mance. In order to I understand Contaminant ions corresponding to other manufacturers by ESI mass leaching behavior of plastic tubes, polypropylene glycol (PPG), polyeth- spectrometry, in the positive mode, an electrospray ionization mass ylene glycol (PEG) and slip agents showed highly contaminated mass spectrometric investigation was car(e.g. erucamide) were found to dom- spectra, due to the high sensitiviriedHence, out inthe our laboratory with some inate thetheir mass spectrum of ergoty of technique. These contamimaterial used by manufacturer 1 and in 2 for furnish wrong information of this the target compounds in ESI brands available in the mar- leach cristine, when these tubes were used nants maydue further biological tubesof is tubes very much unstable, as frequent out issues and MALDI mass spectral studies to theirpossess low quality with high MS grade solvents were seen. revealed ket.even The results revealed that the for This the preparation. activity and are therefore a potential materials. Eppendorf Tubes are shown to be a good alternathat these may be manufactured polymer tive since they are manufactured high quality virgin poreference standard ergocristine either pre- by recycled Eppendorf Safe-Lock Tubes are source offrom assay-specific confounding or that possible leach out of surface occurred. lypropylene. Additionally, slip agents, biocides or plasticizer pared in aEppendorf Tubes® result- coating found to be a good alternative for artifacts. are neither comprised in the raw material nor are they used ed in high quality mass spectra with usage in sensitive mass spectrometThe results demonstrate that solvent-extractable contamiin production. Thus, we conclude that Eppendorf Safe-Lock nants from plastic labware used in research and developTubes are the best substitute for glass consumables in mass ment can be introduced into physical and biological assays spectrometry (ESI and MALDI) based analysis. during routine compound management liquid-handling reference processes. brandsspectra other than of Eppendorf could standard ergocristine (molecular weight 609 g/mol) FigureThe 1 usedMass

incubated in Eppendorf Tubes. Product and precursor ions are labeled in green.

Product ions - 208.1 m/z - 223.2 m/z - 251.2 m/z - 268.1 m/z - 290.2 m/z - 305.4 m/z - 325.3 m/z - 348.2 m/z - 365.3 m/z - 592.4 m/z

Intensity, cps

[M+H]+

[M+Na]+ [M+K]+

a) Eppendorf Safe-Lock Tubes, 1.5 mL (Lot V126403P)

[M2+H]+ [M2+Na]+

Introduction The introduction of new ionization methods in mass spectrometry with improved detection limit has made it possible to detect many contaminants in measurable concentrations. This has increased the need to understand where these interferences come from and how they can be identified. Separation and detection technique has the potential to introduce new contaminants into the analytical system. It is therefore no coincidence that modern analytical chemistry takes advantage of ultrapure chemicals and reagents and ultraclean sample handling containers whenever possible to minimize any potential and unwanted background interference. In addition, all routine modern analytical methods following good laboratory practices (GLP) will include blank tests such as system, solvent, method, matrix and equipment blanks.1 Worldwide, polymer-based consumables are very much popular and have been accepted as a substitute for glass consumables for most of the research applications in laboratories. In particular, disposable plasticware such as test tubes are routinely used in all proteomics laboratories. The use of high quality materials in manufacturing of standard consumables such as glass vials and plastic test tubes etc. is always challenging for companies. Besides this, another major problem for the production plants is to keep the composition unaltered from batch to batch. Disposable plastic labware is ubiquitous in contemporary pharmaceutical research laboratories. It is routinely used for chemical compound

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FEATURE storage and during automated liquid-handling processes that support assay development, high-throughput screening, structure-activity determinations and liability profiling.2 Further, disposable plastic labware is also reported as a potential source of bioactive contaminants.3 In our work on common contaminants in electrospray ionization mass spectrometry (ESI-MS), a large number of interferences have been observed and identified.4 Moreover, significant work by Keller et al.1, published on contaminants encountered in mass spectrometry is noteworthy. The present application note describes the leach out behavior of polymeric consumables accompanied by mass spectrometry detection for undesirable ion or contaminants, probably the plasticizers and polypropylene glycol. However, this report does not interpret specific techniques that allow elimination of certain background interferences. The present note demonstrates that these manufacturing agents leach from different reaction tubes (laboratory plasticware) into reference standard and can have profound effects on results.

Materials and Methods Preparation of standard samples (ergocristine) in different tubes Different disposable plastic tubes were utilized to investigate the leaching behavior of polymer materials and additives used in manufacturing. Three different Eppendorf Safe-Lock Tubes have been taken: DNA LoBind Tube (1.5 mL; Lot Z138810G) and normal Safe-Lock Tubes (1.5 mL; Lot V126403P and 2.0 mL; Lot A143437J). Two 1.5 mL tubes from other manufacturers (named with MF1 and MF2) were used. A 1 ppm reference standard (ergocristine (Sigma-Aldrich®) was prepared in MS grade methanol (1.0 mL each), (Lichrosolv®, Merck). The standard solution was added into the different tubes followed by vortex shaking at room temperature for one minute. Then it was injected as a sample into MS to obtain the MS fingerprint. Prior to injecting samples, a blank run using the methanol directly taken from the container was carried out.

Mass spectrometry analysis After vortex shake, the ergocristine sample in methanol from each tube was drawn through a 1.0 mL Hamilton® syringe and injected at a rate of 10 μL/min using a Model 11 Syringe Pump (Harvard

Apparatus®, USA) into TurboIonSpray® source of mass spectrometer (API 3000 LC/ MS/MS, AB Sciex). Instrument control and data acquisition were performed using Analyst® software version 1.4.1 (Applera Corporation, USA).

The mass spectrometer was operated in Q1MS in positive mode (ESI). The rest of the parameters were taken as default values. The positive and negative ion modes were used to record the mass spectra in the range of 100-1500 amu.

The TurboIonSpray voltage was set at 5500 V for positive ion mode; source temperature kept at 200 ºC throughout the run. Zero-air was used as nebulizer gas at 60 psi. Nitrogen was used as both curtain gas and CAD gas.

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APPLICATION NOTE I No. 282 I Page 4

Figure 1

Mass spectra of reference standard ergocristine (molecular weight 609 g/mol) incubated in Eppendorf Tubes. Product and precursor ions are labeled in green.

[M+H]+

Intensity, cps

Product ions - 208.1 m/z - 223.2 m/z - 251.2 m/z - 268.1 m/z - 290.2 m/z - 305.4 m/z - 325.3 m/z - 348.2 m/z - 365.3 m/z - 592.4 m/z

[M+Na]+ [M+K]+

[M2+H]+ [M2+Na]+

b) Eppendorf Safe-Lock Tubes, 2.0 mL (Lot A143437J)

[M+H]+

Intensity, cps

Product ions - 208.1 m/z - 223.2 m/z - 251.2 m/z - 268.1 m/z - 290.2 m/z - 305.4 m/z - 325.3 m/z - 348.2 m/z - 365.3 m/z - 592.4 m/z

[M+Na]+

[M+K]+ [M2+H]+ [M2+Na]+

c) Eppendorf DNA LoBind Tubes, 1.5 mL (Lot Z138810G)

NOTE I No.ergocristine 282 I Page 6 Figure 1: Mass APPLICATION spectra of reference standard (molecular weight 609 g/mol) incubated in Eppendorf Tubes. Product and precursor ions are labeled in green.

Table 1

Precursor ion scan of reference standard ions observed (positive) in ESI-MS. Table 1: Precursor ion scan of reference standard ions observed (positive) in ESI-MS. Ions selected (m/z)

Ions observed

208.1 223.2 251.2

610.4 [M+H]+, 592.4 [M+H-H2O]+, 268.2, 305.4 610.4 [M+H]+, 592.4, 348.1 592.4, 610.4 [M+H]+

268.1

610.4 [M+H]+, 592.4 [M+H-H2O]+

290.2 305.4 325.3 348.2 365.3 592.4 632.4 648.4

632.4 [M+Na]+, 1241.7 [M2+Na]+ 592.4, 610.4 [M+H]+, 1241.7 [M2+Na]+ 610.4 [M+H]+, 592.4, 1219.7 [M2+H]+ 592.4, 610.4 [M+H]+, 632.4 [M+Na]+, 1219.7 [M2+H]+ 632.4 [M+Na]+ 1219.7 [M2+H]+ 1241.7 [M2+Na]+ 1257.6 [M2+K]+

Acknowledgement

Results and discussion A 1 ppm ergocristine reference standard (prepared in MS grade methanol in each tube) was kept for vortex shaking in three different Eppendorf Safe-Lock Tubes of 1.5 to 2 mL capacity. All the three lots V126403P and Z138810G of 1.5 mL each and A143437J of 2 mL capacity showed significantly higher signal for reference standard with lowest noise level. In addition, [M+H]+ ion corresponding to m/z 610.4 was the most prominent peak observed in Eppendorf Safe-Lock Tubes giving a minimum signal for the common adduct ions such as [M+Na]+ and [M+K]+ at m/z 632.4 and m/z 648.4, respectively (Fig. 1a-c). The marker ions present were m/z 610.4 [M+H]+, 632.4 [M+Na]+, 648.4 [M+K]+, 1219.7 [M2+H]+, 1241.7 [M2+Na]+ and 1257.6 [M2+K]+ (table 1). Based on the mass spectrum, Eppendorf Safe-Lock Tubes give highest signal when used for sensitive MS and MS/ MS analysis. In Figures 2a+b, the mass spectral information of the tubes from manufacturer 1 (MF1) and manufacturer 2 (MF2) are shown. It revealed the presence of a large number of fragment ions indicating possible interference of polymeric materials in spectral analysis. The spectra of reference standard recorded after one minute shake in MF1 showed a higher signal with minimum noise level with marked presence of m/z 437.3 ([A9B+Na]+, [C2H4O]nH2O, PEG) and 453.4 ([A9B+K]+, [C2H4O] nH2O], PEG), 360.4 (erucamide) followed by unidentified peaks at m/z 288.4, 316.3, etc. On the other hand, MF2 represents a prominent contaminated spectral profile. Among the reference standard peaks, the contaminants present were m/z 409.3 ([A8B+K]+; PEG), 425.3 ([A7B+H]+; polypropylene glycol or PPG), 795.5 ([A13B+Na]+; PPG) and

Continued on page 15

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Laboratory Focus July 2013

FEATURE

BY TOM ARNEMAN

Transforming IT in the R&D Laboratory The IT requirements of the modern research laboratory are increasingly complex, often chaotic, delaying the discovery and promotion of new products. Despite the massive impact of a novel compound on corporate and patient healthcare, researchers’ energy is increasingly spent on IT responsibilities. Simply making the lab’s IT related systems operate efficiently takes up to 20 per cent of the average scientist’s day. Meanwhile finding, processing and sharing data drains additional hours per week away from core responsibilities, further delaying time to market and forcing less informed decisions. Nowhere else in the life science value stream are the opportunities for improvement as great as within laboratory IT. The complexity of IT in the lab makes it extremely different from the rest of the organization. In the lab, a given scientist may rely on hundreds of applications – from home-grown analytics to large, inte-

Figure 2

grated enterprise applications. These software platforms integrate at varying levels with costly scientific instruments, which themselves run on high-performance internal and external clusters designed to generate and make sense of “Big Data.” Despite the critical role IT plays in drug discovery, transformational management of IT within the lab has been a challenge for the industry: • There remains a gap in the skill set and models offered by IT service providers to address laboratory complexities. • Quick wins are possible but real change is dependent on long-term relationships which establish trust through demonstrated value in the drug discovery process. • An advocate with a deeper understanding of the differences in laboratory information management is required to secure necessary budgets and organizational support for in-lab initiatives.

Figure 1

The Lab as No Man’s Land Consider the life science IT support model and its relationship to the researcher. In most cases a large-scale, multi-year contract covers a majority of IT support, including enterprise applications and the help desk. These contracts are specifically aligned to support the office worker. Within the

lab, there are service providers focused on instrument support such as preventive maintenance and incident resolution, but these providers also draw the line at managing lab IT. Practically, this leaves a gap in the support process including instrument-connected PCs and related software that control the environment. To address an IT-related problem, a lab owner may start by placing a call to the corporate help desk. The help desk is often the face of a loosely coupled set of internal and external service providers including: facilities, infrastructure, software vendors, instrument manufacturers, application specialists and office IT representatives. There is no end-to-end responsibility resulting in significant delays in project deliverables and issue resolution. Also, without a specific knowledge of the lab requirements as they relate to the drug discovery, critical considerations like virus protection, data availability and connectivity may be overlooked. Most often this process results in the scientists’ taking time to coordinate and resolve issues themselves, developing “shadow IT” teams within the labs. This rocky relationship is by no means a one way issue. Scientists need to understand and appreciate the value of highly experienced IT support. The right partnership between the lab and IT results in a reduced loss of data, increased data availability, increased utilization of expensive assets, and the most up-todate scientific capabilities. When the

July 2013 Laboratory Focus www.laboratoryfocus.ca

FEATURE relationship works efficiently and effectively, lab IT work can be shifted from the scientist to a focused, responsible, IT-knowledgeable team. Ultimately, scientists are able to spend more time on science, delivering new products to market faster. Overall lab IT has a massive impact on scientist productivity, asset utilization, data availability and security. A focused, dedicated team aligned to lab requirements is a clear opportunity to fill the gap in lab computing.

Opportunity for Innovation With establishment of an experienced lab IT support team, the possibilities for increased productivity through innovation rapidly improve. A foundation of clear and proactive support for scientists creates the opportunity to improve lab mobility through tablets, increase asset utilization through asset sharing, and expose data to decision makers in real time. These steps toward the Lab of the Future can become the focus of an embedded and trusted lab IT support team. For example, lab analysts regularly report spending more than 50 per cent of their time on finding, collecting and cleaning data. Providing solutions to automate delivery of key data to decision makers is perhaps the most important role of IT in the lab. Likewise, mobility is shifting where and when scientists monitor, discover and document their research. The next generation of science will be mobile – and the industry needs to lay the groundwork for this evolution now. Beyond building this technological foundation, focusing on lab IT improvements can be a first step in transformational management for the company. Excellent support of lab IT demonstrates that management understands the value of inlab efforts on the ability to bring new products to market. Delays in the lab mean delays in getting new drugs to patients and higher costs for both patients and the drug company. There is an increasingly clear justification to delivering differentiated lab IT support: • Allow scientists to spend more time on science and shift IT responsibilities to a lower cost, dedicated support team; • Increase asset utilization through streamlined onboarding, move and security management; • Increase the availability of timesensitive information, driving faster decisions with significantly less effort; • Focus on innovation rather than maintaining a Break-Fix environment, setting a foundation of trust and partnership between IT and the lab; and

• Encourage a transformational environment of management and development.

A Specialized Partnership So how can these goals be realized? There are three key factors in brokering the required partnership between the laboratory and IT. The first step is to provide a single point of responsibility for lab IT on behalf of the laboratory customer. The service should approach the relationship as a partner in the lab’s efforts rather than an arms-length service. Any new service will take time to establish. A dedicated support team will see a significant increase in support requests and an openness to more strategic involvement within six to nine months of service initiation. Figure 2 highlights a three times increase in support requests achieved by one pharmaceutical company after implementing a differentiated lab IT support model. As trust was built between the lab and the dedicated IT support group, scientists were able to shift work to IT, allowing them to refocus their efforts on drug discovery. Next, the support team must be staffed with experienced, lab-knowledgeable individuals. The lab IT staff members need to understand the complex stack of instruments, network, PCs and software which deliver the lab’s results. In addition to having a passion for lab operations and core technical ability, these individuals typically need to go through a training process to develop the appropriate level of understanding required for the space. To best serve the lab, this differentiated IT team should have the same level of expertise in lab IT as the scientists and analysts they support. With the appropriate expertise, the time required to resolve incidents will drop dramatically. Likewise, this knowledge reduces the lab’s reliance on outside vendors, whose interests may conflict with best practices for securing and managing the lab environment. Figure 2 shows the time required to resolve incidents before and after an experienced lab support team took ownership of the lab. Finally, data must be the priority of the service. Data management includes both the basic security and collection of generated experimental results, as well as the analysis and sharing of findings. The basics include the back-up and recovery processes, comprehensive security and well-managed PC health. Data is the life blood of drug discovery and must be managed as the organization’s most critical asset. Based on these processes working well, the service

can then focus on processing and delivering data. For example, shifting IT’s role from application management to data enablement is the future. One major pharmaceutical company implemented technology that saved users 30 minutes per day. Across 1,000 users, this company has achieved over 10 per cent more scientific capacity per year. IT has a critical role to play in the drug discovery process. Start by laying a foundation of an experienced, dedicated team to establish value and partner with scientists. Building off the positive results of this partnership, scientists can then begin to innovate with a focus on best in class use of data. With this formula, companies can foster an environment that encourages discovery and begin the transformational process necessary to bring them to the next phase.

Tom Arneman has spent his career identifying and implementing IT best practices in the Life Sciences. He has been instrumental in helping companies improve their data management systems, connect with a diverse array of partners, and streamline their business processes. Currently he is president of Ceiba Solutions, a global products and service company.

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BELLUS Health.................................... 5.........................www.bellushealth.com Caldedon Labs................................... 5......................www.caldeonlabs.com Canadian Society for Chemical..................................................................... Technology........................................ 9................ www.cehminst.ca/profdev Ceiba Solutions ................................. 14.................... www.ceibasolutions.com Diba Industries ................................. 16...............................www.dibaind.com DynPort Vaccine Company LLC............. 5...............................www.csc.com/dvc Egenix, Inc. ....................................... 6.............................www.egenixinc.com Eli Lilly and Company........................... 5..................................... www.lilly.com Eppendorf........................................ 20.......................... www.eppendorf.ca Helix BioPharma Corp......................... 6.................... www.helixbiopharma.com Hibernia Management and.............................................................................. Development Company Ltd................... 4.................................www.hibernia.ca Mandel............................................ 11...............................www.mandel.ca Medicago Inc...................................... 5............................ www.medicago.com MEI Pharma, Inc................................. 6..........................www.meipharma.com Mettler Toledo.................................. 16.....

www.ca.mt.com/ca/en/home.

html Qu Biologics ...................................... 6.......................... www.qubiologics.com Stem Cell Therapeutics ...................... 4......................www.stemcellthera.com Thallion Pharmaceuticals Inc................ 5............................... www.thallion.com Therapure Biopharma Inc..................... 5....................... www.therapurebio.com Toronto Memory Program .................. 5.......www.torontomemoryprogram.com Transition Therapeutics Inc.................. 5........ www.transitiontherapeutics.com VWR................................................. 2.................................. www.vwr.com Waters Corporation........................... 16.............................. www.waters.com Wyvern Scientific ........................... 11....................... www.wyvernsci.com Xenon Pharmaceutical......................... 5..................... www.xenon-pharma.com

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Laboratory Focus July 2013

FEATURE Continued from page 12

APPLICATION NOTE IMass No. 282 Ispectra Page 5

Figure 2

of reference standard ergocristine (molecular weight 609 g/mol) incubated in Tubes of manufacturers 1 and 2. Product and precursor ions are labeled in green. Contaminants are labeled in purple.

Contaminants Product ions - 208.1 m/z - 223.2 m/z - 251.2 m/z - 268.1 m/z - 290.2 m/z - 305.4 m/z - 325.3 m/z - 348.2 m/z - 365.3 m/z - 592.4 m/z

[M+H]+



PEG

erucamide

Intensity, cps

PEG

[M+Na]+ [M2+H]+ [M+K]+ [M2+Na]+

a) Tubes 1.5 mL from Manufacturer 1 (MF1)

PEG

[M+H]

 PEG

[M+Na]+

PPG PPG [M2+H]+

b) Tubes 1.5 mL from Manufacturer 2 (MF2) Figure 2: Mass spectra of reference standard ergocristine (molecular weight 609 g/mol) incubated in Tubes of manufacturers 1 and 2. Product and precursor ions are labeled in green. Contaminants are labeled in purple.

811.5 ([A13B+K]+; PPG). However, peaks which remain unidentified in MF2 were m/z 274.3, 302.4, 230.4, 318.3, 330.5, 512.6 and 540.6 (Fig 2b). Notably, adduct ions such as 632.4 [M+Na]+ and 648.4 [M+K]+ were found in very low abundance. Hence, the material used by manufacturer 1 and 2 for their tubes is very much unstable, as frequent leach out issues even with high MS grade solvents were seen. This revealed that these may be manufactured either by

The authors are grateful to Prof. Ram Rajasekharan, Director, CSIRCIMAP for encouragement and constant support to carry out this work, and to DST New Delhi for the project grant.

References

Intensity, cps

Product ions - 208.1 m/z - 223.2 m/z - 251.2 m/z - 268.1 m/z - 290.2 m/z - 305.4 m/z - 325.3 m/z - 348.2 m/z - 365.3 m/z - 592.4 m/z

Acknowledgement

Contaminants =?

The results demonstrate that solvent-extractable contaminants from plastic labware used in research and development can be introduced into physical and biological assays during routine compound management liquid-handling processes.

recycled polymer or that a possible leach out of surface coating occurred. The results demonstrate that solvent-extractable contaminants from plastic labware used in research and development can be introduced into physical and biological assays during routine compound management liquid-handling processes. The used brands other than Eppendorf could furnish wrong information of the target compounds in ESI and MALDI mass spectral studies due to their

low quality materials. Eppendorf Tubes are shown to be a good alternative since they are manufactured from high quality virgin polypropylene. Additionally, slip agents, biocides or plasticizer are neither comprised in the raw material nor are they used in production. Thus, we conclude that Eppendorf SafeLock Tubes are the best substitute for glass consumables in mass spectrometry (ESI and MALDI) based analysis.

1. Keller BO, Sui J, Young AB, Whittal RM. Interferences and contaminants encountered in modern mass spectrometry. Anal Chim Acta 2008; 627:71-81. 2. Watson J, Greenough EB, Lett JE, Ford MJ, Drexler DM, Belcastro JV, Herbst JJ, Chatterjee M, Banks M. Extraction, identification, and functional characterization of a bioactive substance from automated compoundhandling plastic tips. J Biomol Screen 2009; 14(5):566–572. 3. McDonald GR, Hudson AL, Dunn SM, You H, Baker GB, Whittal RM, Martin JW, Jha A, Edmondson DE, Holt A. Bioactive contaminants leach from disposable laboratory plasticware. Science 2008; 322(5903):917. 4. Chanotiya CS. Contaminants in ESI-MS study. 2011; Unpublished work.

To see this story online visit http://www. laboratoryfocus. ca/?p=1375

NEW PRODUCTS Mass Spectrometer Shimadzu introduces the new MALDI-7090™ MALDI TOF-TOF mass spectrometer targeted for proteomics and tissue imaging research. Innovative technology incorporated into the MALDI-7090, such as ASDF™- Axial Spatial Distribution Focusing, delivers high-resolution MALDI MS/MS for accurate compound characterization. This, in combination with proprietary solid-state laser technology, true 2 kHz acquisition speed in all modes (MS and MS/MS), an integrated 10-plate loader and newly designed MALDI Solutions™ software, sets a new benchmark in MALDI TOF-TOF design. With its 20 keV high-energy CID capability, the MALDI-7090 efficiently produces additional fragment ions to further enhance characterization. Comprising a powerful range of tools for method development, acquisition, data processing and interpretation, MALDI Solutions software allows automatic and manual control of the MALDI-7090 and has been designed to provide a flexible platform in the hands of both novice and expert users.

Web: www.ssi.shimadzu.com

Sample preperation Thermo Fisher Scientific, Inc. has introduced the Thermo Scientific Prelude SPLC sample preparation and liquid chromatography system, developed to make analysis of target compounds in complex biological matrices routine for clinical research and forensic toxicology laboratories. The Prelude SPLC system is designed to enhance the cost effectiveness of LC-MS/MS instrumentation by automating sample preparation and increasing mass spectrometer throughput. Automation can minimize variability inherent in manual sample preparation procedures while also reducing sample preparation time and effort. The device is designed to negate problems caused by sample matrix interference while capturing analytes of interest. This kind of sample clean-up can enhance MS quantitative analysis by reducing ion suppression.

Web: www.thermoscientific.com/prelude

Columns Waters Corporation has introduced a new family of 1.6 micron solid-core UltraPerformance LC® Columns that provide higher efficiency and allows laboratories to produce greater amounts of information faster with every chromatographic separation. CORTECS™ Columns are available in C18, C18+ or HILIC chemistries. The columns come in 30 unique column configurations and feature a solid, impermeable silica core encased in a porous silica outer layer where the interactions between the stationary phase and the analytes occur. The CORTECS C18 Column is a general-purpose, high-efficiency, reversed-phase column offering balanced retention of acids, bases, and neutrals at low and midrange pH. The CORTECS C18+ Column is a general-purpose reversedphase column with a positively charged surface that delivers excellent peak shape for basic compounds at low pH. The CORTECS HILIC Column is designed for the retention of extremely polar analytes while offering orthogonal selectivity versus C18 columns.

Web: www.waters.com/cortecs

July 2013 Laboratory Focus www.laboratoryfocus.ca

Pipettes The Mettler Toledo manual Rainin Pipet-Lite XLS+ and electronic Rainin E4 XLS+ offer users durable, lightweight liquid ends and new mechanical designs that all but eliminate hand strain while ensuring the highest channel-to-channel consistency. This combination of improved ergonomic comfort helps pipette operators work more comfortably and reduce the risk of error and potentially expensive rework. Reduced weight and lower pipetting/tip-ejection forces – combined with improved balance – reduce operator fatigue during intensive 96-well plate work. Enhanced reliability ensures data integrity. And operators concerned about cross-contamination will appreciate XLS+’s reduced stiction (piston stickiness), which helps to eliminate splash-up. The Pipet-Lite XLS+ and E4 XLS+ models are available in volumes up to 300 µL.

Web: www.mt.com/rainin-mc.

Benchtop equipment The SI600C cooled shaking incubator is the latest addition to the Stuart range of benchtop science equipment. The SI600C has all the features of the SI600 shaking incubator, with the addition of a separate recirculating chiller to extend the achievable temperature range. The original Stuart SI600 is a combined shaker and incubator, ideal for cell cultures. With the inclusion of a Stuart SRC4 chiller, (or one of an equivalent specification) the SI600C incubator can now run at 15˚C below the ambient temperature of the room, to a minimum internal temperature of 5˚C. The incubator can therefore be introduced into a whole new range of applications, such as cell-based protein expression, which often involves reduction of the culture temperature. During heating and cooling with the SI600C, temperatures are very accurately controlled. Separate controls for temperature and speed reduce the risk of accidental temperature adjustments, and USB communication allows long term tracking of the incubator’s temperature. The SI600C cooled shaking incubator can hold up to six 2L flasks of various types without requiring tulip clamps or tools. The flasks are securely held on a retractable, flexible platform, allowing easy access to samples at the back of the chamber. Users can also purchase stainless steel tube racks, which magnetically couple to the instrument. Biocote antimicrobial protection guards against contamination and reduces the risk of sample loss.

Web: www.stuart-equipment.com

Standard probes Diba Industries has introduced a new line of standard probes that allow engineers to speed up the design phase of projects and shorten the lead times associated with manufacturing custom probes. Diba’s standard probes are made of 316 stainless steel with 200 microlitre internal volume capacity and are capable of reaching the bottom of most sample tubes. Diba offers three versions of standard probes: standard drawn, with no internal diameter treatment; DP3™ polished and PTFE lined. DP3 is Diba’s proprietary polishing process which minimizes carryover by reducing internal diameter roughness by a factor of two to three micro-inches. PTFE lined probes offer an unbroken fluid path with no joints back to the pump.

Web: www.dibaind.com

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September 9-12

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NOVEMBER November 3-8 AIChE 2013 Annual Meeting Venue: San Francisco, CA Tel: 800-242-4363 Fax: 203-775-5177 Email: jeffw@aiche.org Web: http://www.aiche.org/

AAPS Annual Meeting Venue: San Antonio, TX Tel: 703-248-2800 Fax: 703-248-5582 Email: Meetings@aaps.org Web: http://www.aaps.org/ Meetings_and_Professional_Development/Calendar/2013/2013_AAPS_ Annual_Meeting_and_Exposition/

Fourth BioMarine International Business Convention Venue: Halifax, NS Email: contact@biomarine.org Web: http://www.biomarine.org/

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September 15-18 EnviroAnalysis 2013 Conference Venue: Toronto, ON Tel: 613-232-6252 Fax: 613-232-5862 Email: enviroanalysis@cheminst.ca Web: http://www. enviroanalysis2013.ca/

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Laboratory Focus July 2013 www.laboratoryfocus.ca

Canada’s medical lab science community shines at

LABCON 2013 From May 10 to 13, Canada’s medical laboratory professionals gathered in Victoria, British Columbia to attend LABCON 2013. As the Canadian Society for Medical Laboratory Science’s (CSMLS) national conference, the event was an opportunity for lab professionals from across the country to learn and network with their peers. Considered the ‘must-attend’ event of the year, LABCON is the place to see and be seen in the medical lab industry. The conference brings together lab professionals, managers, directors, educators and students to share information and to learn about the latest innovations and trends in their field. Its three days of workshops, speakers and seminars make the conference one of Canada’s most prominent lab industry events. This year was no exception. Held in Victoria for the first time, LABCON 2013 saw 538 attendees taking advantage of the conference’s 49 sessions on professional development and innovation. In addition to the traditional lecturebased presentations, this year also featured new presentation formats, including a panel presentation and roundtable discussion. “The theme for the event was different,” says Michael Grant, team leader, communications at the CSMLS. “It was about bringing together different perspectives and trying to harness the collective wisdom of the community. We wanted to go beyond traditional lecture-based sessions where people are passive recipients of information, and enable a lot more collaboration and discussion within the sessions. That was a real focal point for this year.” The conference also hosted a number of insightful plenary speakers, including a presentation by Dr. Martin Whale, executive medical director for the Vancouver Island Health authority on May 11. His presentation, titled “Leadership for Improvement: What Works for You?” looked at leadership for improvement and innovation in the healthcare sector and beyond – and what we need to better support innovation in Canada. On May 12, the morning plenary session was Michelle Hoad on “Advocacy: Extreme Makeover Edition” outlining how, over the years, the CSMLS has reformulated its message to make sure it gets government attention. The session was an opportunity for attendees to learn about what skills were needed to build their own provincial advocacy message. May 13 featured a plenary session from Christine Nielsen, who discussed “Generations 2.5: Managing Across Generations,” looking at key behavioral differences between the generations, and how to improve relationships across the divide. Beyond the learning aspect of the event, the event helps build up Canada’s medical lab science community. “The lab can be a stressful place at times,” says Grant. “An important aspect of LABCON is to get lab professionals out of the lab to refresh and refocus, so they can return to the lab armed with new knowledge, ideas and energy.” Also new this year, LABCON ran a contest over social media. From Facebook comments and tweets using the hashtag #LABCON2013, a winner was selected to receive a free new iPad mini. For more conference highlights and pictures of the event, check out http://labcon.csmls.org. Next year’s conference, LABCON 2014, will be held on June 21 to 23 in Saskatoon, Saskatchewan.

APP REVIEW LabAssistant

From IDEX Health & Science https://itunes.apple.com/us/app/labassistant/ id422667472?mt=8 Developed for the iPhone and iPad, LabAssistant is a reference tool for chemists and any scientist who works with chemicals in a lab. With information compiled by IDEX Health & Science, a multinational liquid subassembly and precision component manufacturer, the app has a listing of chemical materials on it that, when checked, will tell users if another material is chemically compatible with it, making it a potentially useful tool for scientists. The problem with the app, however, is while it is very helpful, some design functions hold it back from being a truly invaluable app. The biggest flaw is the lack of a search functionality, making navigation a tedious task as the app requires users to manually scroll up and down to find what he/she is looking for. Furthermore, the list of materials leaves much to be desired as the listing that the app has is definitely not comprehensive. LabAssistant has some really good ideas but poor execution both contentwise and functionality really hold this free app back.

ChemSpider

From Molecular Materials Informatics https://itunes.apple.com/us/app/chemspider/ id458878661?mt=8 https://play.google.com/store/apps/details?id=com.mmi.android. chemspider&hl=en ChemSpider from Molecular Materials Informatics is a chemical database with information from Britain’s Royal Society of Chemistry. The app’s design functionality is simple but serviceable as it allows users to search chemical compounds by either name or structure. The most interesting feature of this app is the compound structure viewer as it allows users to view structures using the Molecular Materials’ diagram editor. The app is pretty barebones but there’s little doubt that it can be useful for scientists and as it’s free there can be no complaints about the price point. The decision to make the app available for both iOS and Android devices also helps ChemSpider and as such it is recommended.

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World class Support Exceptional support for your Eppendorf New Brunswick™ ULT Freezer Eppendorf New Brunswick Freezers provide you peace-of-mind with our unparalleled service and support. With our TCA-3 independent, remote temperature monitoring system you are guaranteed reliable sample protection 24/7. The small pod provides each user a secure login to monitor their ULT freezer anywhere at anytime!

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Laboratory Focus July 2013

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