PHARMACEUTICAL
CLINICAL
CHEMICAL
w w w. l a b o r a t o r y f o c u s . c a Improving Cell Culture Process Through Continuous Monitoring Page 10
FOOD
ENVIRONMENT
NOVEMBER/DECEMBER 2014 Volume 18, Number 4
Simultaneous Protein Quantitation and Lipid Content Analysis in Biological Samples Page 12
R&D News.......................... 1 Pharma Notes..................... 5 New Products................... 15 Calendar........................... 17 App Reviews...................... 18
DEVELOPING THE BATTERY OF THE FUTURE CLS SCIENTISTS EXPLORE NOVEL EXPERIMENTAL TECHNIQUES, MATERIALS
Canadian Light Source industrial staff scientists Jigang Zhou and Toby Bond conduct research on battery cells using the IDEAS beamline. Their research and collaborations could lead to the development of safer, cheaper, more powerful, and longer-lasting batteries for everything from phones to electric vehicles.
The search for the next generation of batteries has led researchers at the Canadian Light Source synchrotron to try new methods and materials that could lead to the development of safer, cheaper, more powerful, and longer-lasting power sources to be used in almost everything, from vehicles to phones.
Publications Mail Registration Number: 40052410
“Typically, battery research involves cooking chemicals together to create new materials,” said Dr. Jigang Zhou, a CLS industrial staff scientist. “The performance of these materials is measured by testing the current, voltage, charge time and number of charge cycles the materials can take. Essentially,
you take a stab in the dark and see how good your aim was.” But there are problems with this method, and researchers are still uncertain why some materials work better than others. So Zhou and other researchers are using the synchrotron to examine these materials in a whole new way. If you think of a typical AA battery, the kind you would find in most TV remotes, there is a positive and a negative end called an electrode. Although a number of materials can be used for these electrodes, Zhou and his team are using a novel lithium-nickel-maganese-oxide (LMNO) material on the positive electrode that could provide batteries with significantly higher voltage.
While the higher voltage of this material can offer a real advantage, it tends to dry out the electrolyte – a liquid necessary for batteries to work properly. Understanding the role that each element in LMNO plays is critical to furthering his research into why the electrolyte dries up. Synchrotron X-rays allows for the visualization of the LMNO in such fine detail that he can identify where the material is breaking down the electrolyte liquid, and determine what is happening and how to prevent the breakdown in those places. For the negative electrode however, silicon is a promising and cheap material that researchers are also having success with. “Silicon offers the potential for a higher capacity battery that could hold more charge storage per gram when compared to conventional batteries,” he said. “Such a battery could work longer after a single charge.” Zhou adds “the capacity for silicon is 10 times greater than current negative electrode materials.” However, this material comes with its own challenges. When silicon is used in a battery, its volume changes more greatly between when the battery is fully charged and when it has used up its charge. These changes in volume during charging cycles cause the battery to break down over time, so researchers are working on ways to make silicon more stable so it can be used commercially. Zhou believes that since there are currently no batteries on the market using silicon-LMNO electrodes, research into perfecting these materials could lead to new, better batteries. To see this story online visit http://www.laboratoryfocus. ca/?p=2677
Liquid nitrogen isn’t the most friendly place for lab labels. That’s why Brady FreezerBondz™ are tested and re-tested in the harshest lab conditions. Whether facing liquid nitrogen, freezers or even the heat of autoclaves, FreezerBonz are designed to adhere to frozen tubes and vials down to - 196ºC and work across frosted, frozen or room temperature surfaces. Want to test it yourself? Visit BradyCanada.ca/lab to request a free sample.
#stickysituationlab
www.laboratoryfocus.ca Laboratory Focus
3
November/December 2014
DISCOVERY OF NEW THERAPEUTIC TARGET TO PREVENT THE INVASION OF CANCER CELLS A team of researchers at the IRCM, led by Jean-François Côté, have discovered a potential new therapeutic target that prevents the invasion of cancer cells. The discovery could have a significant impact on breast cancer treatment. Their breakthrough was published by the scientific journal Molecular and Cellular Biology. The researchers are interested in understanding the molecular details involved in metastasis, which is the spread of cancer from one organ to another. This harmful process accounts for nearly 90 per cent of can-
cer patient deaths. “We investigated a molecule called Axl, which is detected at the surface of cancer cells and is known to be involved in various types of invasive cancer,” says Dr. Côté, director of the cytoskeletal organization and cell migration research unit at the IRCM. “In fact, a high amount of Axl on breast tumours is closely associated with metastasis and a poor prognosis for patients. The molecule’s mechanisms remain poorly understood, but we are now excited to have found how it works inside the cell.”
Jean-François Côté and Afnan Abu-Thuraia (Photo: IRCM)
RESEARCHERS DISCOVER POSSIBLE CAUSE OF COMMON DEMENTIA Researchers at the Krembil Neuroscience Centre say they have potentially discovered a major cause of common dementia. In this type of dementia, there is damage to the white matter (nerve fibres) of the brain apparent on computerized tomography (CT) and magnetic resonance imaging (MRI) scans of older individuals. Approximately 50 per cent of older individuals have evident white matter damage on their medical imaging scans. For most patients, these changes are harmless but when this damage is severe, it can cause impairment. Previous studies have already established that the more white matter disease there is in the brain, the more likely patients are to have symptoms of dementia such as cognitive impairment or changes in behaviour. What was not understood is why this white matter disease develops – the traditional assumption was that it might be the result of the natural aging process. Krembil researchers hypothesized that the white matter dis-
ease, also called leukoaraiosis, may actually be the result of many tiny unnoticed strokes accumulating over time – a finding that points to a potentially treatable form of dementia. Their research was published in the journal Annals of Neurology. The researchers conducted an intensive study to observe the development of this white matter disease over a short period of time, rather than on an annual basis – the interval at which previous studies have performed repeat brain imaging. The study involved five patients with white matter disease undergoing detailed MRI scanning of their brains every week for 16 consecutive weeks. The weekly MRI scans revealed new tiny spots arising in the brain’s white matter that were, based on their MRI appearance, characteristic of small new strokes (cerebral infarcts). The lesions had no symptoms but, with time, came to resemble the existing white matter disease in the subjects’ brains. In the study’s random sampling, the majority of subjects had this phenomenon: Tiny strokes occurring without symptoms, and developing into the kind of white
NEWS
“With this study, we showed that Axl activates a novel chain of events that leads to cell invasion,” adds Afnan Abu-Thuraia, first author of the article and doctorate student in Dr. Côté’s laboratory. “More precisely, we demonstrated that Axl modifies a protein known as ELMO in order to robustly induce the spread of breast cancer cells.” “Our results allowed us to identify ELMO as a new potential therapeutic target to prevent the invasion of cancer cells and the formation of metastasis,” concludes Dr. Côté. “This discovery could eventually lead to the development of new treatments for triple negative breast cancer.” Triple negative breast cancer accounts for 15 to 20 per cent of all breast cancers and is associated with a poor prognosis and increased risk of metastasis to vital organs. It is characterized by the absence of three key receptors typically targeted by standard breast cancer treatments. As such, no targeted therapy is currently available for triple negative breast cancer. To see this story online visit http://www.laboratoryfocus. ca/?p=2682 matter disease that causes dementia. “We were surprised by the study findings” said Dr. Daniel Mandell, neuroradiologist, joint department of medical imaging, Toronto Western Hospital and the principal investigator of the study. “The findings suggest that the tiny, silent strokes are likely much more common than physicians previously appreciated, and these strokes are likely a cause of the agerelated white matter disease that can lead to dementia.” Unlike degenerative types of dementia where there are no treatments, this type, based on vascular disease, is more treatable as it is caused by tiny episodes affecting the blood vessels in the brain over time. It may be possible to prevent or stop this process. Although more research is needed to further investigate these findings with a larger sample size, if most white matter disease is found to be caused by these tiny strokes, it could eventually lead to interventions to delay its progression in the brain. To watch a time lapse video of strokes occurring in the brain visit http://youtu.be/J3fb0CaDpEk? list=UUB-segCeC3f2DcEY6HtaavQ To see this story online visit http://www.laboratoryfocus. ca/?p=2684
PUBLISHER/EDITOR-IN-CHIEF Terri Pavelic STAFF WRITER Shawn Lawrence CONTRIBUTING WRITERS Adriana Nori de Macedo Aawista Chaudhry Chandreyee Das Nuno Goncalves Peter Traynor Philip Britz-McKibbin NATIONAL ACCOUNT MANAGER Marcello Sukhdeo GRAPHIC DESIGNER Elena Pankova CONTROLLER John R. Jones MARKETING MANAGER Mary Malofy CIRCULATION DIRECTOR circulation@promotive.net OFFICE: 24-4 Vata Court Aurora, ON L4G 4B6 Phone: 905-727-3875 Fax: 905-727-4428 E-mail: laboratory_focus@ promotive.net SUBSCRIPTION INQUIRIES circulation@promotive.net Fax: 905-727-4428 Laboratory Focus is published 4 times per year by Promotive Communications Inc. Legal Depository: National Library of Canada ISSN 40052410 Subscription rate in Canada $35/year; USA $60/year; other countries $100/year. All rights reserved. No part of this publication may be reproduced without written consent. Publications Mail Registration Number: 40052410 Return undeliverable Canadian addresses to circulation dept: 24-4 Vata Court Aurora, ON L4G 4B6 E-mail: circulation@promotive.net All opinions expressed herein are those of the contributors and do not necessarily reflect the views of the publisher or any person or organization associated with the magazine. If you would like to order hard copy or electronic reprints of articles, contact Sandra Service 905-727-3875 x228 reprints@promotive.net www.laboratoryfocus.ca
4
November/December 2014 Laboratory Focus www.laboratoryfocus.ca
NEWS
MAKING STRIDES IN NEUROENDOCRINE TUMOUR RESEARCH The Cancer Research Society in partnership with the Carcinoid NeuroEndocrine Tumour Society of Canada (CNETS Canada) is awarding $120,000 to Dr. Trevor Pugh and his team of researchers from University Health
Network, located in Toronto, to continue their study on gastrointestinal and pancreatic neuroendocrine tumours. Their research aims to find a molecular signature that would identify patients who could benefit from a group of
drugs called mTOR inhibitors. Well-differentiated neuroendocrine tumours belong to a group of rare cancers that are incurable once they have metastasized and are not amenable to surgery. An alternative treatment option is
conventional chemotherapy but it has been shown to have limited effect on these neuroendocrine tumours. A more targeted approach is the use of a group of drugs called mTOR inhibitors that have shown anticancer activ-
GE Healthcare Life Sciences
ÄKTA start ™
An easy-to-learn and easy-to-use system to eliminate the • Purify tagged proteins and antibodies easily • Gain insight from real-time monitoring • Evaluate and share your results
Contact your VWR Life Science Representative for more information! 1.800.932.5000 / ca.vwr.com
ity in patients with advanced pancreatic cancer. “Our goal is to find a molecular signature that would allow us to distinguish the patients who would benefit from mTOR inhibitors from those who would not,” explained Dr. Pugh. “With this objective, we are sequencing the DNA and RNA of each gene in the tumours of patients while they are undergoing treatment with an mTOR inhibitor, and comparing this data to tumours removed prior to treatment. This will allow us to observe the genes that change in response to the treatment.” He adds that these results will help in understanding how neuroendocrine tumours act during treatment, and the goal will be to develop new ways to adapt the treatment of these types of cancer and others that are treated with similar medications. “Our study brings together clinical and basic research teams to observe genetic changes of neuroendocrine tumours in patients undergoing active treatment with targeted therapies. Such knowledge will enable physicians to select patients most likely to benefit from mTOR inhibitors and expedite alternative treatments in patients unlikely to respond,” added Dr. Pugh. To see this story online visit http://www.laboratoryfocus. ca/?p=2679
www.laboratoryfocus.ca
Laboratory Focus November/December 2014
PHARMA NOTES
Cardiome Pharma Corp. (Vancouver, BC) has released the results from its Phase 3 clinical study conducted with BRINAVESS® (vernakalant intravenous, RSD 1235) in the Asia-Pacific (A-P) region. The study was originally planned to recruit 615 patients, however the study was completed after randomizing 123 patients. The study remained sufficiently powered and it achieved the primary endpoint, showing that of the 111 treated patients with recent-onset atrial fibrillation (AF) lasting 3 hours to 7 days, 53% of those receiving an IV dose of BRINAVESS converted to normal heart rhythm within 90 minutes, compared to 12% of placebo patients (95% CI; 23%, 58%, p<0.001). The A-P study data suggests that BRINAVESS was generally welltolerated in the targeted patient population. In the 30 day interval following drug administration, serious adverse events occurred in 6 (11%) placebo patients and 7 (13%) patients dosed with BRINAVESS. Potentially drug-related serious adverse events occurred in 1(2%) patient receiving BRINAVESS. There were no cases of drug-related torsades de pointes, a wellcharacterized arrhythmia which is an occasional side effect of many current antiarrhythmic drugs. The study was initiated in August 2010, and was carried out in 35 centers in Korea, Taiwan, Hong Kong and India. Sanofi company Genzyme (Toronto, ON) reports it has enrolled the first patient in its multicenter Phase 2 clinical trial evaluating the company’s investigational infusion therapy vatelizumab in patients with relapsing remitting multiple sclerosis (RRMS). The trial, called EMPIRE, is designed to assess the efficacy of vatelizumab vs. placebo in RRMS patients. The safety,
tolerability and pharmacokinetics of vatelizumab will also be assessed. Vatelizumab is a humanized monoclonal antibody that targets VLA-2, a collagenbinding integrin expressed on activated lymphocytes. The mechanism of action of vatelizumab is not known, although it is hypothesized to block VLA-2 on activated immune cells, leading to interference with collagen-binding in areas of inflammation, and thus may reduce the inflammatory cascade in MS. Select Canadian clinics in Ontario and Quebec will participate in the research and enroll appropriate candidates. Regenerative medicine company RepliCel Life Sciences Inc. (Vancouver, BC) reports it has submitted a clinical trial application to Health Canada requesting clearance to initiate a Phase 1/2 clinical trial investigating the use of RCT-01 to treat patients suffering from chronic Achilles tendinosis. The study entitled, “A randomized, double-blind, multi-centre dose-finding study to evaluate the efficacy and safety of RCT-01 in men and women with unilateral, chronic Achilles tendinosis” addresses the inherent deficit of ac-
tive fibroblasts required to regenerate healthy functioning tendon after injury. The trial, to be conducted at the University of British Columbia, will measure several safety and efficacy endpoints following a single injection of RCT-01. Qu Biologics Inc., a biotechnology company developing Site Specific Immunomodulators (SSIs) that aim to restore the body’s immune system, reports that an independent Data Safety Monitoring Committee (DSMC) has reviewed the safety data generated from 30 patients (50 per cent enrollment) from Qu Biologics’ current Crohn’s disease clinical trial and has recommended that the trial continue as planned with continued safety monitoring. The trial is taking place in Vancouver, BC, and is now 60 per cent enrolled. More information about the trial can be found at www. qucrohnstrial.com. The Centre for Drug Research and Development (CDRD) (Vancouver, BC) has joined forces with four major translational health research organizations to launch a global collaboration in the field of translational research in
medicine. The collaboration will see Therapeutic Innovation Australia (TIA), the European Infrastructure for Translational Medicine (EATRIS ERIC) and USbased National Institutes of Health’s National Center for Advancing Translational Sciences (NCATS) working in partnership with CDRD to identify and seek solutions to major bottlenecks in this key area of medical research. Zymeworks Inc. (Vancouver, BC) and Eli Lilly and Company say they have expanded their existing licensing and collaboration agreement originally announced in January 2014. The collaboration focuses on the development of an undisclosed number of novel bi-specific antibody therapeutics using Zymeworks’ proprietary Azymetric™ platform. The two parties say they will now work towards generating new cancer immunotherapies, with Lilly opting to expand the collaboration by up to potentially US $375 million in milestones and other payments, plus tiered sales royalties based on countryby-country intellectual property, and sales to include development of several immuno-modulatory bi-
5
specific antibodies against multiple targets. Toronto-based AvidBiologics Inc. and the National Research Council of Canada (NRC) are collaborating on one of the most promising advances in the fight against cancer: antibody-drug conjugates (ADCs).The recently signed research and licensing agreements will enable both organizations to continue developing a series of ADCs targeting breast, lung, and head-and-neck cancers. Antibody-drug conjugates combine the targeting attributes of antibodies with the cancer-destroying properties of drugs that are toxic to cells. Unlike chemotherapy, ADCs specifically seek and destroy cancer cells, with minimal impact on healthy cells. Since the start of the project in early 2013, NRC’s antibody expertise has helped advance AvidBiologics’ lead treatment more rapidly. By late September 2014, the data helped convince Avid’s investors to close a new financing round. Avid will now complete confirmatory preclinical testing for its lead candidate in anticipation of its initial clinical trial in 2015.
Chemicals for QC, R&D and Production
• High Purity Solvents for LC/MS, HPLC, GC • Standardized and Custom Solutions • Thin Layer Chromatography (TLC) Plates • ACS Grade Solvents, Acids and Dry Chemicals call: 877-225-3366 fax: 905-877-6666 service@caledonlabs.com
6
November/December 2014 Laboratory Focus www.laboratoryfocus.ca
NEWS MCMASTER-LED STUDY IDENTIFIES SIMPLE PREDICTOR OF DIABETES RISK
CANADIAN COMPANY DEVELOPS 60-SECOND EBOLA TESTING KIT Rapid infectious disease diagnostic test developer bioLytical Laboratories says it has successfully developed a pre-clinical prototype diagnostic test for the rapid detection of antibodies to the Ebola Zaire strain responsible for the current outbreak in West Africa. The prototype is based upon the company’s flagship product INSTI rapid test platform, which is capable of providing results in as little as 60 seconds as a HIV1/HIV2 antibody test. “We are very excited about what our research and development team has been able to accomplish in such a short period of time,” says bioLytical’s CEO Dr. Christopher Shackleton. “There is clearly a pressing need for
a diagnostic test that can rapidly and accurately detect the presence of this potentially deadly infection as early as possible and in diverse testing environments.” He adds that the speed of the INSTI platform should offer considerable advantages as compared to slower point-of-care assays when it comes to the screening of large numbers of subjects in the field as well as in those settings where time is a significant constraint such as travel points of entry. To see this story online visit http://www.laboratoryfocus. ca/?p=2686
Become a certified chemical technologist (cct)
McMaster University researchers have discovered a simple way to predict an adult’s future risk of developing Type 2 diabetes.Their findings, published in the journal Diabetologia indicate that the blood glycaemia level at one hour after drinking a glucose solution of 75 grams beats every known Type 2 diabetes prediction model published to date. “Having the one-hour plasma glucose (1h-PG) information alone is sufficient to identify people who are more at risk for developing Type 2 diabetes in the future,” explained David Meyre, the paper’s senior author and an associate professor in the department of clinical epidemiology and biostatistics at McMaster’s Michael G. DeGroote School of Medicine. “Only 30 per cent of non-diabetic middleaged adults in the study displayed a high 1h-PG (higher than 8.9 mmol/l), but they accounted for 75 per cent of all future diabetic cases”. This measurement, Meyre says, known as one-hour plasma glucose (1h-PG), may help to identify high-risk subjects in the general population for inclusion in Type 2 diabetes prevention programs. He added that such prevention programs, if applied on a global scale, may save billions of dollars and improve the lives of millions of people. The discovery could prove important as the prevalence of Type 2 Diabetes has more than doubled globally over the past 30 years, and the rate of death among patients with diabetes is about twice as high as among those without it. Problems related to the disease include blindness, heart attacks, kidney disease, and infections leading to amputations. Meyre added: “Applying mass screening programs in populations
cCT certification offered by the Canadian Society for Chemical Technology (CSCT) • Is recognized nationally by employers • Is based on Canada-wide technology standards • Allows for greater career mobility CSCT members in good standing who have attained the required combination of education and experience in chemical technology need only apply once for the cCT for the one time fee of $25 plus tax. Certification remains valid as long as CSCT membership is maintained.
for more information or to apply go to
www.chem-tech.ca/cct
David Meyre and Akram Alyass
and enrolling people at risk in a simple and inexpensive lifestyle modification program, in cooperation with the family doctor, may prevent up to half of future Type 2 diabetes cases. Another exciting perspective worth investigating is whether 1h-PG predicts future complications of Type 2 diabetes.” Using new mathematical methods to capture data on nearly 5,000 northern Europeans from two independent longitudinal studies, the researchers found that 1h-PG alone outperformed the popular but more complicated prediction models based on multiple clinical risk factors, including age, sex, body mass index, and family history of diabetes. The research team, which included colleagues from McMaster and universities in Lund, Sweden, and Helsinki, Finland, wrote that the value of the 1h-PG for Type 2 diabetes prediction in multi-ethnic longitudinal studies still needs to be assessed because the rate of the disease varies by ethnicity. However, they are fairly confident in the transferability of their results to other populations. “Colleagues from the University of Texas recently reported that one-hour plasma glucose was predictive of future Type 2 diabetes risk in Mexican Americans and this is encouraging,” said Akram Alyass, the study’s first author and a PhD student in computational science at McMaster. The study was funded by several research foundations, hospitals and universities in Finland and Sweden. Meyre holds a Canada Research Chair in Genetic Epidemiology. To see this story online visit http://www.laboratoryfocus. ca/?p=2688
www.laboratoryfocus.ca
7
Laboratory Focus November/December 2014
FEATURE B Y ADR I A N A N O R I D E M A C E DO , A A WI STA C H A U D H R Y A ND P HI L I P BR I T Z -M C KI B B I N *
Nutritional iodine status determination by capillary electrophoresis for population health
NUTRITIONAL IODINE DEFICIENCY: A Re-emerging Public Health Concern? Iodine is a trace inorganic micronutrient required for human health as it is used for biosynthesis of iodinerelated hormones (e.g., L-thyroxine) by the thyroid gland.1 Due to the serious impact of iodine deficiency disorders, many countries have introduced mandatory iodization of table salt as a public health measure to prevent goitre, cretinism and chronic disease risk in the population. Mild to moderate iodine deficiency is particularly a concern for pregnant and lactating women due to its impact on fetal and infant brain development. Indeed, iodine deficiency remains the leading cause of preventable cognitive impairment in children with over two billion of the global population at risk. Since over 80 per cent of salt intake is now derived from processed foods in most industrialized countries, changes in dietary patterns may contribute to iodide inadequacy since the food industry is not mandated to use iodized salt.2
Chronic exposure to environmental uptake inhibitors (e.g., perchlorate, thiocyanate and nitrate), a reduction in the use of iodine additives in dairy foods and commercial breads, and the increased popularity of “low-salt” products to reduce hypertension may also contribute to the re-emergence of nutritional iodine deficiency. As a result, there is an urgent need for continuous monitoring of iodine status in the population. ICP-MS involves expensive infrastructure and high operating costs with limited selectivity since inadequate maternal iodine intake has been shown to cause adverse effects on child cognitive development even in countries with mild iodine deficiency.3
Continuous Monitoring of Population Iodine Status: Urinary Iodide Concentrations Urinary iodide concentrations (UIC) are often used for assessment of recent iodine intake in the population
since over 90 per cent of ingested iodine is excreted in the urine.4 Although 24 hr urine specimens provide a more accurate indicator of daily iodine intake, in most cases random single-spot urine specimens from subjects are measured more conveniently. In this case, median values of urinary iodide concentrations are used to estimate iodine nutrition on a population level that corrects for variations in day-to-day dietary intake and urinary volume. According to the World Health Organization, adequate iodine nutrition in the population corresponds to median UIC levels ranging from 0.70-1.57mM for adults. Methods for UIC measurements require high selectivity, sensitivity, sample throughput and robustness when applied to large-scale epidemiological studies. A colorimetric assay based on the Sandell-Kolthoff (S-K) reaction is the most widely used method for determination of UIC that is based on iodide-catalyzed reduction of ce-
ric ion, Ce (IV) in the presence on arsenite, As (III) under acidic conditions.5 Limitations of this kinetic spectrophotometric assay include poor selectivity, high variability and use of toxic reagents while requiring complicated sample workup to eliminate redox-active urinary interferences, such as ascorbic acid. Alternatively, inductively coupled plasma-mass spectrometry (ICP-MS) offers improved selectivity and excellent sensitivity for UIC determination.6 However, ICP-MS requires high infrastructure and operating costs and it has limited selectivity since total iodine content is measured in a urine specimen, including iodinecontaining metabolites, such food additives, drugs and radiocontrast agents. In addition, ion suppression effects can lead to bias when iodinebased isotopic internal standards are not used during analysis due to large variations in urine composition.7 As a result, high efficiency separations are critical for resolution of iodinebased species present in urine (e.g., iodate, 3-iodo-L-tyrosine, L-thyroxine, amiodarone etc.) while also reducing matrix/spectral interferences and/or time-consuming sample workup. Although ion-exchange chromatography has been applied for urinary iodide determination, poor separation efficiency and long analysis times has limited its applicability to population-based iodine nutrition studies.
8
November/December 2014 Laboratory Focus www.laboratoryfocus.ca
FEATURE Figure 1
Pooled 24 hr urine sample
NDS (IS)
Table 1.
35
Absorbance
30 25
> 500-fold excess of nitrate & 106 -- fold excess of chloride in human urine
20 15 10 5
[Iodide] (µ M)
Condi on
Nitrate
Dilute urine in water & inject
Iodide
Chloride
0 2
0
4
Time (min)
6
8
10
Three representa ve urine iodide profiles
A Needle in Haystack?
5
2.66 µM iodide 1.58 µM iodide 0.79 µM iodide
Nitrate
4 Absorbance
I-
Internal standard
3
Thiocyanate
2
Excessive intake Adequate intake Mild deficiency
1 0 6.0
6.5
7.0
7.5
8.0 Time (min)
8.5
9.0
9.5
Condi&ons:)
A robust yet selective method for determination of nutritional iodine status by CE with UV detection. 8 Diluted urine samples are analyzed directly by CE under reversed polarity with sample selfstacking as a way to boost sensitivity for sub-micromolar detection of urinary iodide without spectral/matrix interferences as depicted in series of electropherograms. Two relevant iodide uptake inhibitors are also measured simultaneously in urine, namely nitrate and thiocyanate. Quantitative measurements of urinary iodide concentration levels are needed when assessing the prevalence of iodine deficiency in the population based on criteria set by the World Health Organization.
Capillary Electrophoresis with Sample Self-stacking for Urinary Iodide Capillary electrophoresis (CE) offers a versatile microseparation format for inorganic ion analysis due to its short analysis times, low reagent costs and minimal sample requirements. Miniaturization and/or multiplexing of electrophoretic separations in a microfluidic or capillary array format greatly increases sample throughput. However, concentration sensitivity is limited in CE due to the small injection volume on-column and the narrow optical path length that is insufficient to detect sub-micromolar levels of urinary iodide. Also, a rigorous method optimization and validation is required to ensure reliable performance as required for large-scale epidemiological studies. Recently, a robust yet selective method for nutritional iodine status determination was introduced when using CE with UV absorbance detection under reversed polarity.8 Sample self-
stacking was used as a novel on-line sample preconcentration technique that boosts sensitivity for direct analysis of urinary iodide without sample pretreatment. However, a-cyclodextrin (a-CD) is required as a selective additive in the background electrolyte in order to resolve trace levels of iodide from up to a million-fold excess of chloride in urine as shown in Figure 1. Formation of an ion inclusion complex with a-CD during electromigration is critical for slowing the electrophoretic mobility of iodide as a necessary condition for sample self-stacking under acidic conditions, where high levels of urinary chloride and dihydrogen phosphate in the BGE function as the leading and terminating co-ions, respectively.8 Moreover, urinary nitrate and thiocyanate levels can also be monitored simultaneously by this method since they are relevant iodide uptake intake inhibitors derived from chronic exposure to certain foods, contaminated water and/or smoke.
Figure 1 highlights that iodide migrates as an extremely sharp and resolved peak in the electropherograms despite the long hydrodynamic sample injection that fills approximately one third of the total capillary length prior to voltage application. In this case, the iodine nutrition status of a population can be directly assessed based on quantification of UIC levels among large numbers of subjects that can vary considerably due to differences in dietary intake and hydration status. This assay offers excellent linearity, accuracy and intermediate precision for reliable determination of iodide in human urine specimens over 29 days.8
Summary and Future Outlook Universal iodization programs represent one of the most successful public health policies to reduce goitre, cretinism and related iodide deficiency disorders. However, household iodized table salt may no longer
be the most effective approach to ensure adequate iodine intake to the population. Selective, simple, rapid yet robust methods are thus needed for monitoring the prevalence of mild to moderate iodine deficiency in support of global health initiatives. CE offers improved selectivity for urinary iodide determination in comparison to the S-K colorimetric assay and ICP-MS while being prone to fewer spectral or matrix interferences. Moreover, urine samples are analyzed directly without complex sample handling procedures that also allows for assessment of nitrate and thiocyanate environmental exposure. On-line sample preconcentration of sub-micromolar levels of iodide in human urine is realized by CE with UV detection when using sample self-stacking with a-cyclodextrin under reversed polarity and acidic conditions. Future work will evaluate the long-term performance of CE for reliable determination of urinary iodide, including round-rob-
www.laboratoryfocus.ca in trials and inter-laboratory validation studies. Also, population-based assessment of the nutritional iodine status of Canadians will be examined due to changing demographics and dietary/lifestyle patterns notably among highrisk groups, including pregnant women, infants and grade-school children.
References 1. Pearce, EN, Andersson M, Zimmermann MB. Global iodine nutrition: Where do we stand? Thyroid 2013, 23: 523-528. 2. Zimmermann MB, Andersson M. Update on iodine status worldwide. Current Opin. Endocrinol. Diabetes Obes. 2012, 19: 382-7. 3. Bath SC, Steer CD, Golding J, Emmett P, Rayman MP. Effect of inadequate iodine status in UK pregnant women on cognitive outcomes in their children: results from the Avon Longitudinal Study of Parents and Children (ALSPAC). Lancet 2013, 382: 331-7. 4. Vejbjerg P, Knudsen N, Perrild H, Laurberg P, Andersen S, Rasmussen LB, Ovesen L, Jørgensen T. Estimation of iodine intake from various urinary iodine measurements in population studies. Thyroid 2009, 19:1281-6. 5. Gnat D, Dunn AD, Chaker S, Delange F, Vertongen F, Dunn JT. Fast colorimetric method for measuring urinary iodine. Clin. Chem. 2003, 49: 186-8. 6. Shelor CP, Dasgupta PK. Review of analytical methods for the quantification of iodine in complex matrices. Anal. Chim. Acta 2011, 702: 16-36. 7. Dyke JV, Dasgupta PK, Kirk AB. Trace iodine quantitation in biological samples by mass spectrometric methods: the optimum internal standard. Talanta 2009, 79: 235-42. 8. Macedo AN, Teo K, Mente A, McQueen MJ, Zeidler J, Poirier P, Lear SA, Wielgosz A, Britz-McKibbin P. A robust method for iodine status determination in epidemiological studies by capillary electrophoresis. Anal. Chem. 2014, 86:10010-5.
9
Laboratory Focus November/December 2014
Philip Britz-McKibbin is an Associate Professor at the Department of Chemistry and Chemical Biology at McMaster University with research interests spanning separation science, mass spectrometry, metabolite profiling, metabolomics, biomarker discovery and
clinical chemistry. Adriana Nori de Macedo is a third year graduate student and recipient of an Ontario Trillium Scholarship, and Aawista Chaudhry is a senior thesis student in the Chemical Biology program. Their research activities have focused on the development of new methods for iodine status
determination as required in large-scale epidemiological studies. Correspondence: Dr. Philip Britz-McKibbin, Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON, L8S 4M1, Canada E-mail: britz@mcmaster.ca Fax: +1-905-522-2509
FEATURE To see this story online visit http://www. laboratoryfocus. ca/?p=2694
Quality Products... Guaranteed
Quality Products for Your Lab at Affordable Prices! Our lab products have taken part in side-by-side comparative tests at Universities, Pharmaceutical, Government and Research Institutions around the globe. Wyvern products were found to be as good as, or better than, the name brands and were considered a higher value due to their low cost. Our Filtration Products are Designed, Manufactured and Certified in Accordance with ISO 9001
Wyvern Scientific - Distributed By Mandel
www.mandel.ca 1-888-883-3636 info@mandel.ca
10
November/December 2014 Laboratory Focus www.laboratoryfocus.ca
FEATURE BY PETER TRAYNOR
Improving Cell Culture Process
Through Continuous Monitoring
Biologic drug development is exponentially more complicated than traditional small molecule development.
While small molecules are produced using comparatively simple chemical processes, biologics are developed using genetically engineered microorganisms, which means that production processes must continuously monitor the health and development of these organisms. In addition to increased process complexity, the biologic drugs themselves present characterization challenges, also known as “large molecule” drugs, biologics are large proteins with masses as high as 150,000 Daltons, which is more than 150 times the upper mass limit of small molecule pharmaceuticals. The process and product complexity of large molecule drugs makes them much more difficult to develop than small molecules. This is especially so for producers of generic biologics, while traditional small molecule drugs are relatively simple to characterize and reverse engineer, biologics are a different story. Characterizing such a large protein is a very difficult task, and developing a process that produces an identical protein – which includes custom engineering a microorganism specifically for that process – is nearly impossible, especially without access to the cell line that produced the original drug. For obvious competitive reasons, producers of generic biologics are almost never given access to that line.
Because reverse engineering a biologic is so difficult and the final product so complex, generic biologics are never exactly the same as the branded original they’re trying to reproduce. To reflect this difference, generic biologics are called “biosimilars,” they achieve the same effect as the original drug, but they do not have a precisely identical protein structure. Biosimilars are also commonly referred to as “subsequent entry biologics” (SEBs) to reflect their position in the market – this term is often used by Health Canada in its regulatory documentation.
Challenges of Biosimilar Development Biosimilar development involves both chemical and biological engineering, which makes it much more complex than the purely chemical processes that produce small molecule drugs. Engineering the microorganisms that will actually produce the biosimilar is an iterative process; researchers hope to get closer to the target protein with each variation of the cell batches’ DNA. Once the cells are producing an acceptable biologic, more cell batches are tested to find the most efficient growth media for the new organism. Only once the microorganism and the growth media are perfected can the process go to production scale.
The faster a lab can make these iterations, the more quickly it will develop a cell population that can produce an acceptable biosimilar. However, because biosimilar research involves living organisms and not just chemical processes, managing multiple variants developing simultaneously is much more difficult than it is in small molecule development. For example, genetically engineered microorganisms are often more sensitive to minor environmental changes – including pH, temperature and light – than purely chemical processes are, and that means that they have more potential failure points during development. The failure of a cell batch can slow down research significantly, so development laboratories must be able to prevent failure by continuously monitoring the health of all cell batches currently in production. To ensure cell health, this monitoring system should, at minimum, be able to detect anomalies and alert staff in real time.
Cell Monitoring Using Mass Spectrometry Gas analysis mass spectrometry is one of the best technologies for monitoring the status of multiple simultaneously developing cell batches. There are bench top mass spectrometers that exist that are designed
www.laboratoryfocus.ca
11
Laboratory Focus November/December 2014
FEATURE specifically to monitor the effluent composition of up to 15 different bioreactors, and they are an ideal choice for biosimilar research and development applications. Very small changes in the relative concentrations of effluent gases leaving the bioreactor – including CO2 and O2 – can provide critical diagnostic information on the health of the microorganisms within the reactor. Gas analysis mass spectrometers measure the composition of the effluent by ionizing its constituent gases and then separating them by their mass-to-charge ratios. Having this information in real time can significantly reduce the accidental loss rate of developing batches, speeding up development and minimizing redundant work. In addition to monitoring batch health, continuous effluent monitoring using gas analysis mass spectrometry can provide scientists with real time respiration metrics. These metrics can help research teams determine the efficiency with which each batch is consuming its growth medium and producing the target protein. More detailed respiration data enable development teams to make highly precise improvements to growth media and process efficiency. While these small efficiencies may seem unimportant at the development scale, they translate into significant cost and time savings once the final process scales up to production.
Figure 1
Analyzer section - operating principles and peak profile
Magnetic Sector Gas Analysis Effective gas analysis mass spectrometers are able to monitor multiple effluent streams simultaneously while producing as few false positives as possible. False positives are a challenge for many mass spectrometry techniques, especially those that require regular calibration to avoid analyzer drift. Because monitoring must be continuous to be effective, even brief periods of miscalibration
or maintenance downtime represent significant problems. This means that analyzer drift and calibration downtime should be key concerns in selecting an effluent analyzer. Magnetic sector mass spectrometers are one of the best choices for effluent analysis because they require minimal upkeep and are highly fault tolerant. Unlike quadrupole mass spectrometers, which modify ion
In addition to speeding up development, this continuous monitoring increases the efficiency of the final process, which translates into significant cost savings when the process scales up to production level.
paths using several different AC and DC electric fields, magnetic sector instruments use a variable magnetic field to influence the trajectory of effluent ions as they pass through the analyzer. After the ions have been separated, they land on a detector that measures them to determine the composition of the gas sample. The output of this analysis is displayed as a series of flat-topped peaks (Figure 1), where the x-axis represents mass and the y-axis represents ion concentration. Unlike quadrupole mass spectrometers, which produce round-topped Gaussian peaks which are easily affected by analyzer drift, the flat-topped peaks of a magnetic sector mass spectrometer allow it to continue producing accurate results when faced with relatively large variations in the ions’ mass position. This inherent fault tolerance makes magnetic sector the perfect choice for continuous effluent monitoring.
Conclusion Multi-inlet magnetic sector mass spectrometers make biosimilar research more efficient by reducing
cell batch loss rate and providing respiration metrics that allow development scientists to improve growth media. These capabilities are important in the development phase, where they help scientists iterate more quickly and develop better production processes. In addition to speeding up development, this continuous monitoring increases the efficiency of the final process, which translates into significant cost savings when the process scales up to production level.
Peter Traynor is the global sales leader, mass spectrometry, environmental and process monitoring with Thermo Fisher Scientific
To see this story online visit http://www. laboratoryfocus. ca/?p=2690
12
November/December 2014 Laboratory Focus www.laboratoryfocus.ca
FEATURE
BY NUNO GONCALVES, CHANDREYEE DAS
Simultaneous Protein Quantitation
and Lipid Content Analysis in Biological Samples Figure 1
IR provides more universal accuracy in protein quantification.
1a)
The ability to rapidly and accurately analyze both proteins and lipids is critical for thousands of laboratories worldwide. 1b)
L
ipid content monitoring is also important because many biological samples are rich in lipids, including adipose tissue homogenates, brain and liver tissue extracts, lipemic samples and breast milk. To effectively measure toxicity and efficacy biomarkers, such as cytokines, cardiovascular disease markers and hormones, the lipids must be removed by fractionation or filtration. During drug discovery and development research, biomarker detection and analysis methods are often strongly influenced by the mode of lysate preparation, and process optimization benefits from in-line monitoring of protein yield and lipid content. This article will first summarize traditional methods of protein and lipid analysis and then describe a method that enables rapid analysis of total protein with simultaneous
monitoring of lipid content, simplifying and improving the analytical process.
Protein Detection and Quantitation Many protein detection methods are available, including amino acid analysis, ultraviolet (UV) spectrometry, colorimetric assays, Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) and densitometry, immunological-based methods, and mass spectrometry.1 There are multiple factors to consider when selecting the best option for a particular application, such as the amount of protein available, concentration of protein in the sample, assay specificity, presence of interfering chemicals in the solvents used, and ease and reliability of the assay method. Protein quantitation methods were first developed in the early 1950s,
1a) Compare to UV280; 1b) Compare to amino acid analysis.
www.laboratoryfocus.ca
13
Laboratory Focus November/December 2014
FEATURE The Direct Detect® spectrometer (EMD Millipore) provides a new approach to protein/peptide quantitation. The benchtop system enables highly accurate infrared (IR)-based measurements of amide bonds in protein chains without relying on amino acid composition, dye binding properties or redox potential. Figure 2
Analysis of protein and lipid content from a single sample measurement.
Because the sample composition and ratio of individual components were unknown, phospholipid analysis was performed using the “Relative Absorbance” mode. For clarity, the intrinsic infrared signal from the membrane (1300-1100 cm-1) was removed from the displayed spectrum.
Figure 3
Calibration curves for structurally diverse lipids prepared using lipid standards
(Avanti Lipids) and the Calibration Method in the instrument software.
when physicists and chemists entered the biology space and applied their techniques to the analysis and measurement of proteins. The Lowry protein assay was the first biochemical assay used for determining the total level of protein in a solution.2 The introduction of this assay was followed shortly by other methods of measurement, including ultraviolet (UV) systems and amino acid analysis. These methods were all able to characterize proteins in water or a very mild buffer solution. The methods used for quantitation began to evolve as protein research became more complex. In 1976, the Bradford assay allowed researchers to study proteins in more native solutions, and used detergents or other reducing agents to keep the proteins soluble.3 The Lowry assay was reinvented to become the bicinchoninic acid (BCA) assay (also known as the Smith assay), which made it more adaptable to the solvents being used in protein research.4 More than 25 years passed, however, without a true innovation in protein quantitation. The Direct Detect® spectrometer (EMD Millipore) provides a new approach to protein/peptide quantitation. The benchtop system enables highly accurate infrared (IR)-based measurements of amide bonds in protein chains without relying on amino acid composition, dye binding properties or redox potential. Proteins are represented within the IR spectrum by nine amide peaks representing different vibrational modes of peptide bond. In particular, the amide I and amide II bonds are unique because of the strength and purity of their signal even in the presence of complex mixtures, reducing agents, and detergents; therefore, these bands are used for
measurement. The accuracy of this system is comparable to amino acid analysis, the gold standard of protein quantitation (Figure 1a and 1b). The Direct Detect® system contains protein detection technology and analysis tools, including a BSA standard curve that comes preloaded on the software. The assay requires only two microliters of sample, which is deposited on an assay-free card, placed in the instrument and then measured. The whole process takes approximately two to three minutes.
Lipid Content Analysis Traditionally, lipid content has been analyzed by extracting dried samples with organic solvents and subjecting the extracts to chromatography or spectrometry.5 However, proteins are not soluble in the organic fraction, and therefore, it is challenging to obtain a reliable assessment of protein and lipid content. In addition, extraction methods can consume large amounts of sample and time. Because the Direct Detect® spectrometer analyzes small aqueous samples (2 µL) spotted on membrane cards, it can use IR spectrometry to determine lipid content in un-extracted samples while simultaneously quantifying total protein in the same measurement (Figure 2). Due to their complex chemical composition, lipids absorb in many different regions of the IR spectrum. Given that each lipid possesses an IR signature uniquely defined by its chemical composition and structure, IR spectroscopy offers a means of qualitative lipid discrimination. The Direct Detect® spectrometer utilizes the C-H symmetric stretching vibrational population between 2870 and 2840 cm-1 to determine lipid or detergent content.
14
November/December 2014 Laboratory Focus www.laboratoryfocus.ca
FEATURE Figure 4
Monitoring total protein content as well as the lipid profile during the preparation of tissue lysate.
Simultaneous analysis via a rapid, easy-to-use approach offers researchers a simple way to qualify the composition of complex samples upstream of more detailed analyses. Conclusion
(A) Total protein extracted from human brain tissue of nondiseased and Alzheimer’s patients. (B) Monitoring of lipid content during detergent-aided protein extraction from human brain tissue of nondiseased and Alzheimer’s patients.
The spectrometer and accompanying Direct Detect® assay-free cards were used to obtain sample concentration measurements. Each card contains four polytetrafluoroethylene (PTFE) membrane positions for sample application and analysis. All measurements were performed using 2 μL of sample per membrane position. Unknown mixtures were analyzed in the “Relative Absorbance” mode, where the system de-
livers information based solely on IR signal strength. Empirical sample concentration values can be determined by interpolation from calibration curves developed for each specific lipid or detergent (Figure 3).
Simultaneous Measurements in Brain Tissue The Direct Detect® spectrometer was used to simultaneously monitor the total protein content and
lipid profile of human brain tissue extracts. Frozen brain tissues from three nondiseased and three Alzheimer’s disease patients (obtained from Analytical Biological Services Inc.) were sliced into aliquots (100150 mg each). Samples were loaded into pre-chilled microcentrifuge tubes containing 500 µL of CytoBuster™ Protein extraction reagent (EMD Millipore), supplemented with protease and phosphatase inhibitors, and kept on ice. Tube contents were homogenized using a glass homogenizer and then transferred back to the microcentrifuge tube. The homogenizer was washed with additional 500 µL of respective prechilled buffers. This fraction was combined with the original sample. Tubes were centrifuged and the supernatant (detergent-soluble fraction 1) was collected. The soft white layer between detergent-soluble fraction and the pellet was resuspended with 500 µL of corresponding buffer, homogenized again and centrifuged. The second detergent-soluble fraction was collected and combined with fraction 1. The protein and lipid content of the combined detergent-soluble fractions, as well as the soft white layer formed between the supernatant and the pellet, were analyzed using IR spectrometry to monitor the efficiency of fat removal and total protein concentration during centrifugal extraction. The collected IR spectra were used to determine the total protein recovery across the various fractions (Figure 4A). The same spectra also showed removal of a fatty fraction from the samples (Figure 4B).
The Direct Detect® spectrometer can be used to analyze protein and lipid content from a single sample measurement. Both types of analysis are important; quantitation of proteins in solution is required in thousands of laboratories worldwide, while lipids constitute the principal structural components of all tissues and represent a key element of biological membranes. Simultaneous analysis via a rapid, easy-to-use approach offers researchers a simple way to qualify the composition of complex samples upstream of more detailed analyses.
References 1. Kurien E and Biji T. (2012) Chapter 3 of Methods in Molecular Biology: Protein Electrophoresis. Goldring A and Dean JP, eds. Humana Press. http:// dx.doi.org/10.1007/978-161779-821-4_3 (accessed October 31, 2014). 2. Lowry, O.H., et al. (1951). J Biol Chem. 193, 265-275. 3. Bradford, M.M. (1976). Anal Biochem. 72, 248-254. 4. Smith, P.K., et al. (1985). Anal Biochem. 150, 76-85. 5. Avanti Lipids Website. https:// www.avantilipids.com/index. php?option=com_content&view =article&id=1377&Itemid=368 (accessed on October 31, 2014).
Nuno Goncalve is Manager of Novel Biomolecular Detection at EMD Millipore. Chandreyee Das, Ph.D. is a Senior Technical Writer, Protein Detection at EMD Millipore.
To see this story online visit http://www. laboratoryfocus. ca/?p=2692
www.laboratoryfocus.ca
Laboratory Focus November/December 2014
Spectrometers
Shimadzu Scientific Instruments introduces the ICPE-9800 Series Simultaneous ICP Atomic Emission Spectrometers for chemical, environmental, pharmaceutical, food, metal and electronics analysis. The series includes the ICPE-9810 (Axial) and ICPE-9820 spectrometers (Dual View). With a photometric system ideal for analyzing a large variety of samples, the ICPE-9800 series spectrometers are vertically oriented and its plasma torch minimizes adhesion of samples on the torch walls, reducing carryover. This allows for simultaneous analysis of trace and high-concentration samples without concern for contamination by simply switching between axial and radial views. The ICPE-9800 Series also features a leading-edge CCD (charge-coupled device) detector with one million pixels. Using this large one-inch sensor, data for all wavelengths is captured as an image on a two-dimensional plane in the same way that a camera captures a photograph. The wavelength can be changed after measurement is complete and all of the data is saved for future review, helping to eliminate measurement errors and reduce the work needed for repeated measurements. With the ICPEsolution Smart Assist software, analysis can be started smoothly every time.
Web: www.ssi.shimadzu.com
Flow Cytometry EMD Millipore, the Life Science division of Merck KGaA has released the guava easyCyte™ 12 flow cytometer. The system has been shown to detect particles as small as 0.2 μm, a significant improvement over typical flow cytometers. This is useful particularly for researchers analyzing small particles and beads, as well as studying bacteria or algae. The guava easyCyte™ 12 flow cytometer uses three excitation lasers to detect up to 12 parameters simultaneously, including 10 fluorescent colors plus forward and side scatter for size and granularity determination. The upgraded lasers and unique scanning technology reduce channel bleedover and significantly improve resolution. Single-sample and multi-sample processing options are offered, and high-throughput analysis is possible with robotic sample trays that automatically handle 96-well micro¬plates and up to 10 sample tubes. The new platform consumes less sample, generates less waste and is easier to maintain than traditional systems.
Web: www.emdmillipore.com/guava.
Software Symbion Systems Inc. announces the release of Symbion QT, Version 2.5, a chemometrics software that provides Parametric Data Cleaning™, a technique which automates the handling of data compromised by excessive noise or other artifacts. Key cleaning parameters are under the control of the analyst, allowing chemometric optimization under a wide range of analytical situations. Parametric Data Cleaning provides important benefits when developing analyzer applications using near-infrared, UV-Visible, mid-infrared and Raman spectroscopy. It is especially appropriate for high-resolution gas-phase analysis.
Web: www.gosymbion.com
NEW PRODUCTS Printers Mettler Toledo introduces its new line of laboratory printers. The new, P-56 and P-58 printers provide high resolution printouts both on paper and self-adhesive labels thanks to thermal direct printing technology. The printers come with 25-year guaranteed fade-proof paper and 10-year guarantee fade-proof labels to ensure the integrity of physical records for years to come. Additionally, the printers come with a built-in real-time clock, with detailed sample information and barcode printing to meet GMP/ISO traceability requirements. With a multilingual user interface and several connectivity options, users can simply plug-in and start printing. All thermal paper and labels supplied by METTLER TOLEDO are phenol-free; in addition labels are resistant to plasticizers, oil, fat and water. Both printer models incorporate RS232, USB, and Ethernet interfaces, with a Bluetooth wireless option so it’s easy to just plug in, power up and start printing. The P-58 model offers additional user applications if needed, such as totaling, formulation and statistics.
Web: www.mt.com
COMPANY & ADVERTISER INDEX COMPANY
PAGE
WEBSITE
Avid Biologics Inc................................ 5........................www.avidbiologics.com BioAlberta.......................................... 6........................... www.bioalberta.com bioLytical Laboratories......................... 4............................. www.biolytical.com BioTalent Canada................................ 6................................www.biotalent.ca Brady............................................... 2................. www.BradyCanada.ca/lab BrandTech......................................... 16.......................... www.brandtech.com Caledon Laboratory Chemicals.......... 5......................www.caledonlabs.com Canadian Society for Chemical..................................................................... Technology........................................ 6.....................www.chem-tech.ca/cct Cardiome Pharma Corp....................... 5............................ www.cardiome.com Children’s Miracle Network............ 17... www.childrensmiraclenetwork.ca Centre for Drug Research.............................................................................. and Development................................ 5......................................www.cdrd.ca EMD Millipore................................... 15.......................www.emdmillipore.com Eppendorf........................................ 20....................www.eppendorfna.com Genzyme............................................ 5................................www.genzyme.ca Hamilton Company............................. 16................www.hamiltoncompany.com Mandel/Wyvern Scientific................. 9................................www.mandel.ca McMaster University.......................... 6.............................. www.mcmaster.ca Mettler Toledo.................................. 15.....................................www.mt.com National Research Council of Canada.... 5..................... www.nrc-cnrc.gc.ca/eng Panasonic Life Science..................... 19.www.us.panasonic-healthcare.com Qu Biologics Inc.................................. 5.......................... www.qubiologics.com RepliCel Life Sciences Inc....................5,6............................. www.replicel.com Resverlogix Corp................................ 6..........................www.resverlogix.com Sartorius.......................................... 16........................... www.sartorius.com Symbion Systems Inc......................... 15..........................www.gosymbion.com VWR................................................. 4.................................. www.vwr.com Xagenic Inc......................................... 6............................... www.xagenic.com Zymeworks Inc................................... 5..........................www.zymeworks.com
15
16
November/December 2014 Laboratory Focus www.laboratoryfocus.ca
NEW PRODUCTS Balances
Pumps
Sartorius introduces the new Entris analytical and precision balance. Covering a weighing capacity from 60 g to 8,200 g with a readability of 0.1 mg to 0.1 g., it is available in 15 models. It comes equipped with a monolithic weighing system featuring external adjustment or an internal, motorized adjustment function. It can also be used for such applications as density determination, animal weighing, counting, conversion and weighing in percent and supplied in the languages German, English, French, Italian, Spanish, Russian and Polish. Additionally, its draft shield and stainless steel parts are easily removable, thereby making the Entris quick and easy to clean.
2/19/2012 10:01 AM Page 1
Web: www.sartorius.com
SRC103
I wish to receive/continue to receive a complimentary subscription to
Yes
LABORATORY FOCUS
No
Format Preference:
Print option
Digital option
Signature:________________________________Date: ____________________________ Name: ____________________________Job Title:_______________________________ Company: _________________________Dept: _________________________________ Business Address : _______________________________________________________ City: _________________________Prov: ________Postal Code: ___________________ Telephone: ___________________________Fax: ________________________________ E-mail: ___________________________________________________________________ On occasion, LABORATORY FOCUS will send third-party information on products & services related to the lab and life science industries. These may be cancelled at any time. Please check here if you do NOT wish to receive these.
JOB TITLE 70 Laboratory Dir. / Mgr. 71 Laboratory Purchaser 72 Laboratory Technician 73 Research Scientist 99 Other:____________________ ____________________________
C75 10 11 12 13 14 15
C87 A B C D
C90
COMPANYs PRIMARY BUSINESS ACTIVITY 50 Industrial Laboratories 51 Academic Laboratories (except medical) 52 Medical Laboratories and Pharmacies within Hospitals and Universities (clinical and research)
55 Government Laboratories 54 Pharmaceutical Companies including Pharmaceutical Wholesalers 57 Private (Independent) Lab 99 Other:____________________ ____________________________
Primary Work Field Aerospace Automotive Biological Sciences Chemicals Electrical/Electronics Energy
16 Environmental Science 17 Food/Beverages/ Agriculture 18 Forensics 19 Genetic Technology 20 Material Science
27 Plastics/Rubber 28 Supplier – Instruments/ Consumables 29 Manufacturing 30 Construction 99 Other: ____________
21 Clinical Sciences 22 Metallurgy 23 Paints/Coatings 24 Paper/Pulp 25 Petroleum 26 Pharmaceuticals
Products Used in your Laboratory Analysis Instruments Basic Lab Equipment Chemicals/Biochemicals Chromatography – Gas
E F G H
Chromatography – Liquid Filtration, Water Purification LIMS Liquid Handling & Sample Prep
I J K L
Microscopes, Optics, Cameras Safety & Hygiene Spectroscopy Testing Systems/Equipment
M Vacuum Equipment
To subscribe to our e-mail newsletters, please check
1 Biotechnology Focus eBulletin 2 Laboratory Focus eBulletin
3 BioPharma 4 BioMedical 5 Health Care
6 Agri-Food 7 Clean Tech 8 Industry Inte
For a quick response please fax: 905-727-4428 or e-mail: circulation@promotive.net
Hamilton Company’s laboratory and sensors division introduces the new Hamilton Precision Syringe Drive 6 (PSD/6); a compact, full-height pump for precision dispensing of small to large volumes. The Hamilton PSD/6 performs all standard liquid handling functions including dispensing, serial dispensing and diluting. The PSD/6 also offers a large range of compatible syringes sizes, and offers enhanced flow stability and increased dispense times making it ideal for applications like flow cytometry and micro fluidics. Designed for simple integration, a variety of mounting configurations are possible for a single unit or a daisy chain of up to 16 pumps. With selectable communication protocols and flexible programming options, every detail of the pump’s performance can be adjusted to accommodate even the most challenging applications. The PSD/6 syringe and valve drive movements are optimized to extend the life and time between product maintenance.
Web: www.hamiltoncompany.com
Pipette tips BrandTech introduces its new line of BRAND pipette tips from BRAND GMBH + CO KG, including sterile, non-sterile, filtered and ultra-low retention tips. The line features a new, environmentally-friendly box and insert system with lids that can hinge or lift off. Tips are manufactured in BRAND’s new state-of-the art clean room and packaged DNA-, RNase-, ATP- and endotoxinfree. Tips fit pipettes from all major manufacturers, including the BRAND Transferpette® S.
Web: www.BrandTech.com .
www.laboratoryfocus.ca Laboratory Focus
NOVEMBER 2014 November 24-26 Genomics: The Power & The Promise Venue: Ottawa, ON Twitter: #powerofgenomics, @ GenomeCanada Web: www.genomecanada.ca
November 25 OSCI Stem Cell Symposium Venue: Toronto, ON Web: http://ontariostemcell.ca/ node/405
November/December 2014
Venue: New York, NY Twitter: @bio1x1 and #BIOCEO15 Web: www.bio.org/events/ conferences/
February 25 BioContactQuebec 2015 Venue: Quebec City, QC Tel: 418 694-8778 Fax: 418 694-0614 Email : mgodbout@hodran.com Web: www.biocontact.qc.ca/
CALENDAR
February 27-March 1 BIOTECanada Investor Summit Venue: Whistler, BC Email: julie.mair@biotech.ca Web: www.biotech.ca
17
MARCH 2015 March 8-12 PITTCON 2015 Venue: New Orleans, LS Twitter: @Pittcon Tel: 412-825-3220 Fax: 412-825-3224 Email: info@pittcon.org Web: www.pittcon.org
November 30-December 5 2014 MRS Fall Meeting & Exhibit Venue: Boston, MA Tel: 724-779-3003 Email: info@mrs.org Web: www.mrs.org
DECEMBER 2014 December 1-3 Canadian Bioeconomy Conference Venue: Toronto, ON Tel: 416-869-1600 Email: l.ehman@greenfuels.org Web: www.cvent.com
December 3-6 2014 World Cancer Congress Venue: Melbourne, Australia Tel: 41 22 809 1811 Email: congress@uicc.org Web: www.worldcancercongress.org
December 6-10
December 9 LSO Annual Fall Symposium Venue: Toronto, ON Web: www.lifesciencesontario.ca/ events/eventsCalendar/ FallSymposium2014.php
JANUARY 2015 January 12-14 Biotech Showcase 2015 Venue: San Francisco, CA Tel: 760 692 5917 Email: krogers@ebdgroup.com Web: www.ebdgroup.com/bts/ index.php
FEBRUARY 2015
CritiCal priority needs for
14
Children’s
hospitals
aCross Canada
eaCh day, there are
4,900
Children
ASCB 54th Annual Meeting Venue: Philadelphia, PA Tel: 301-347-9300 Email: ascbinfo@ascb.org Web: www.ascb.org
Children’s MiraCle network funds
who rely on the support of Children’s MiraCle network
MeMber hospitals in Canada
What is Children’s Miracle Network? Children’s Miracle Network® raises funds for 170 children’s hospitals in North America, 14 of which are in Canada. These hospitals, in turn, use the money where it’s needed the most. When a donation is given, it stays in the community, ensuring that every dollar is helping local kids. These donations have gone to support critical research and training, purchase life-saving equipment, and ensure excellence in care - all in support of our mission to save and improve the lives of children.
February 7-11 SLAS2015 Venue: Washington, DC Tel: 630-256-7527 Fax: 630-741-7527 Email: slas@slas.org Web: www.slas2015.org
February 9-10 Bio CEO & Investor Conference
Learn more at: ChildrensMiracleNetwork.ca
18
Laboratory Focus November/December 2014 www.laboratoryfocus.ca
APP REVIEW
Medscape
By WebMD https://itunes.apple.com/ca/app/medscape/id321367289?mt=8 https://play.google.com/store/apps/details?id=com.medscape. android&hl=en
Canadian stem cell researchers hope new ‘Action Plan’ will cement place in the cell therapy age
B
uilding on a long legacy of leadership in stem cell science, Canadian stem cell advocates, researchers and charities are teaming up on an ambitious new plan that will put Canada at the forefront of the cell therapy age. The goal of the plan is for Canada to lead the way in bringing five to 10 breakthrough therapies to the clinic within 10 years. In total, the Canadian Stem Cell Strategy & Action Plan calls for a $1.5-billion public-private investment, including a $50-million scaled annual commitment by the Government of Canada. Outlined in a new report: Following Through: Realizing the Promise of Stem Cells – A Canadian Stem Cell Strategy & Action Plan (2015-2025), the plan backed by an in-depth study by KPMG has already been endorsed by an international panel of experts. The report outlines how Canada can transform health care, reduce suffering and treat cardiovascular diseases, cancer, diabetes, vision loss, spinal cord injury and other devastating conditions. Canada has a lot going for it in terms of implementing this strategy. For starters, it’s already home to many of the leading researchers in the field. Moreover, Canadians have been at the forefront from its early beginnings as it was two Canadians (Drs. James Till and Ernest McCulloch) who proved the existence of stem cells in the early 1960s. Their finding has in many ways paved the way for subsequent generations of Canadian scientists such as Dr. Sam Weiss, Dr. Janet Rossant, Dr. Andras Nagy, Dr. Michael Rudnicki and a host of others. In addition to our long legacy, Canada also has infrastructure to implement such a plan, with the Stem Cell Network and other such networks encouraging world-class researchers to work in close collaboration for almost 15 years. It will be interesting to see what potential new discoveries come out of this Action Plan. There is no denying that the potential is there to transform health care in Canada and help millions of Canadians.
From the practicing physician to the curious commoner, Medscape is a well-rounded app that has something for everyone. After completing a brief registration, users have access to an abundance of information that ranges in depth and length. The clean user-interface allows easy access to an extensive variety of features that include medical calculators, drug formulary information, as well as the latest in medical news. To accompany the comprehensive articles, tutorials and procedures, Medscape provides high definition videos and pictures. Sharing is only a click away: the app provides a Save and Share article for when you wish to resume reading later, or find something worth passing on to a friend. Medscape’s customizability and variety in its content makes it clear why it is the most downloaded medical app for the iPhone. Add to that the fact that Medscape is free, and you’ve got yourself a standout winner in the medical field.
Starmap
By Fredd https://itunes.apple.com/us/app/starmap/id284408099 Starmap is an interactive app for both seasoned and amateur astronomers. Essentially a portable planetarium, Starmap provides users with a tour of the constellations in a single glace, including 350, 000 stars and 150 galaxies. Starmap proves that perhaps the sky is not the limit after all; the app also provides planets’ satellite views and flowing, detailed graphics. Extensive customisability gives users the unparalleled feeling of holding the universe in the palm of their hands - with custom user location, you can know anything and everything from light pollution in your area to nearby shooting star zones. Consider $4.99 a small price to pay in exchange for knowledge as boundless as the galaxies that surround us. This app is definitely a star.
TwinGuard
®
EXPERIENCE TWICE THE SECURITY
30% more
2x Protection
VIP® Insulation
Simply secure. Give your samples the ultimate protection of patented Twin Guard® technology – two independent systems can individually sustain ultra-low temperatures in the event of a failure, so you can rest easy knowing your valuable work is in good hands. powered by
Learn more at us.panasonic-healthcare.com/twinguard
Impress Yourself The new Eppendorf Cell Culture Consumables The all new product line of Eppendorf Cell Culture Consumables will truly delight your cells. Its outstanding design, reliability and purity is based on more than 50 years of experience. Products created by experts, developed for perfectionists. Impress yourself!
> Unsurpassed quality, clarity, purity and sterility, providing reliable cell culture conditions > Significantly improved design for more safety and consistency > Maximum safety and confidence during storage and transportation
www.eppendorfna.com/cellculture • 800-645-3050 052.A1.0101.B © 2014 Eppendorf AG.
