LC-MSn
David Suzuki Quality vs quantity
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CONTENTS 10 CO2 and Food
Feeling Lucky By Hermione Wilson
By David Suzuki
By Rohan Thakur
The Centre for Gambling Research at UBC gets inside the mind of gamblers while they play.
The drawbacks of using CO2 as plant fertilizer.
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standards guest editorial 5 Canadian news 6 worldwide news 8 Lab ware 21 moments in time 23
Ultra-Fast Drug Screening for Forensic Research Using Toxtyper LC-MSn solution as a key part of drug screening research and services.
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Do the flip!
Learn how psychopharmacogenetics are pushing personalized medicine forward. Education
Closing the gap on job readiness 14
REgional PRofilE Atlantic provinces work together 17
september/october 2017
MoMEnts in tiME Meet the father of pharmacogenetics 23
septeMBer/oCtoBer 2017
LC-MSn
DaviD Suzuki Quality vs quantity
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The DefiniTive Source for Lab ProDucTS, newS anD DeveLoPmenTS
www.labbusinessmag.com
September/October 2017
Propelling drug screening research
17
in the
9
suzuki matters
Zone UBC researchers study gambling’s effect on the brain
Championing the Business of Biotechnology in Canada
MIND GAM ES Personalized medicine meets mental health with psychopharmacogenetics
on twitter at @biolabmag On the Web at www.labbusinessmag.com
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Robert Price
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hat does addiction look like? Picture one. Moss Park in Toronto. At the corner of Queen Street East and Sherbourne Street, just south of the Salvation Army hostel and east of a methadone clinic, men and women shuffle like sleepwalkers, their minds on another plane. Too many have died from overdoses, and so across the street, on the grounds of the park, a safe injection tent now stands. Picture two. Peterborough, Ontario. A man walks his children to the bus stop, then goes home. Years ago, he injured his back at work and became dependent on painkillers. When the government took oxycontin off the market, he switched to heroin. With the kids safe at school, he settles into his chair to get his fix. Picture three. Niagara Falls. A couple on an anniversary trip wanders through Fallsview Casino in the early afternoon. The card tables are empty – it’s too early for serious card sharks – but the slots do steady business with local seniors, who press buttons and watch the colours spin for hours. Not wanting to join the slot-playing seniors, the couple heads to the food court for a coffee. They find a vacant seat next to a man scratching a dozen scratch cards. As he rushes to the convenience counter for another dozen and hope, the couple picks up their coffee and leaves. These are three pictures. A dozen other situations would tell the same story: of people doubly trapped. First by choice or circumstance. Second by addiction. The drug always makes promises. It offers an escape and then sinks chemical hooks into the brain and pulls. Nobody is immune. At some point in our lives we all want to escape. Once the hooks catch, it’s hard to escape. Those who can’t escape addiction live in judgement. We judge the person enslaved by chemicals most harshly. They brought it on themselves, we say. Others we judge differently. We know that under the right circumstances we could end up pressing buttons at a casino or hammered on the couch night after night. Many of us already have addictions, but fortunately our addictions – to booze and cigarettes, excessive spending and compulsive eating – remain discreetly out of the way, affecting nobody except ourselves and those closest to us. Until science can deliver a cure-all for addictive behaviours, addiction will remain wrapped in uncomfortable questions. For example, why do we allow our provincial governments to run lotteries and casinos that prey on addicts? The uncomfortable answer is that we need the money gambling generates. We’ve done the cost-benefit analysis and decided the revenue stream is worth a gambling addict’s suffering. And how much freedom of conscience and choice should we give ourselves if we know so many of us will, through addiction, lose our ability to choose? That cost-benefit analysis has already been tallied. The cost is lives, and we pay it. Alcohol, the saviour of so many dull parties, warps more lives and kills more innocents than any other drug. The cigarette, consummate symbol of coolness and freedom, charges a deadly fee. Just like too many cigarettes will blacken lungs, pornography addictions darken the masturbator’s sexual imagination and lay a heavy cost on the porn star, who will never escape an eternity on the Internet. But we want our freedoms – our booze, our butts, our porn, scratch cards, slots, and whatever other demon has its hooks in us. Most of all, we want the right to choose how to live. Some of us choose more wisely than others – so we don’t pay the price for the freedoms we at first said we wanted.
Robert Price is the former Managing Editor of this publication. Follow him @pricerobertg. www.labbusinessmag.com
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Canadian NEWS Government Opens National Call-out for Research on Primary Agriculture
Employment and Social Development Canada, in collaboration with Agriculture and Agri-food Canada, is looking for research on the primary agricultural sector to support a review of the Temporary Foreign Worker Program’s Primary Agriculture Stream. Canadians with an interest in primary agriculture should submit available research on the primary agricultural sector. Research can be on a number of issues related to primary agriculture and will inform future changes to the program, including methods for determining wages and labour shortages.
Expanding Early Childhood Education in Canada offers Big Benefits
Expanding early childhood education (ECE) and care in Canada would provide sizable benefits, such as improving children’s academic outcomes and future wages, reducing income inequality and bringing many families out of poverty says a new Conference Board of Canada report. It finds that for every $1 spent on expanding ECE enrolment of children less than five years of age to the Organisation for Economic Co-operation and Development (OECD) average would yield close to $6 in economic benefits. Children who receive effective ECE—either through kindergarten, pre-kindergarten, or licensed childcare programs—develop better cognitive abilities, and math and reading skills.
Combined Ontario Universities Research Income Lags National Growth
Research Infosource reports 18 Ontario universities on Canada’s Top 50 Research Universities List recorded combined research income growth of 1.4 per cent, compared with the national research income growth of 2.2 per cent in 2016. A number of Ontario institutions outperformed the national trend: McMaster University, University of Ottawa, Carleton University, Ryerson University, Laurentian University, and Wilfrid Laurier University. Combined research income for Ontario universities in 2016 was $2.7 billion, up from $2.66 billion in 2015. 6
September/October 2017 Lab Business
New Science Committee to Help Meet Needs of Canada’s Researchers
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hen Canada’s scientists have the best support to meet their needs, whether new labs and equipment, access to funding, or opportunities to collaborate with their research peers or train new generations of students—they are able to pursue bold new ideas and make exciting breakthroughs in research. Much of this support comes from funding supplied by Canada’s three federal granting agencies—the Social Sciences and Humanities Research Council of Canada (SSHRC), the Natural Sciences and Engineering Research Council of Canada (NSERC), and the Canadian Institutes of Health Research (CIHR)—and by the Canada Foundation for Innovation (CFI). Though these agencies are vital to Canadian research, more needs to be done to improve how they support scientists and students who are a source of new knowledge, skills development and innovation. That’s why the Honourable Kirsty Duncan, Minister of Science, and the Honourable Ginette Petitpas Taylor, Minister of Health, in October announced the creation of the Canada Research Coordinating Committee (CRCC). In an open letter, the ministers tasked the committee to improve collaboration among the granting councils and the CFI to the benefit of researchers and students across the country. The CRCC will address several of the recommendations made in the Fundamental Science Review, including improving support for international, multidisciplinary, risky and rapid-response research; ensuring better access to funding for young researchers; improving equity, diversity and the capacity of Indigenous communities to conduct research and partner with the broader academic community; and making the research system more nimble so that researchers can seize opportunities with minimal administrative burden. The presidents of the three granting agencies will chair the CRCC on a rotating basis. SSHRC President Ted Hewitt will be the inaugural chair of the committee. The CRCC Chair will work with the presidents of NSERC and CIHR, and with the Deputy Ministers of Innovation, Science and Economic Development Canada and Health Canada to enhance coordination among their agencies and departments. The president of the CFI will attend all CRCC meetings, bringing a valuable perspective on the research infrastructure needs of scientists and scholars. The president of the National Research Council of Canada and Canada's Chief Science Advisor will be invited to participate in CRCC meetings. The ministers are confident the new committee will play an important role in reinvigorating Canada’s support for science to meet the current and future needs of the country's scientists, scholars and students.
Canadian NEWS
Montreal Business School Creates Industrial Research Chair
RBC Renews Commitment to Ontario Science Centre
RBC renewed its three-year commitment as title sponsor of the Ontario Science Centre and its community access programs at the RBC Innovators’ Ball, which took place at the Centre on Nov. 8. The sold out event featured 50 tables of corporate leaders who provided critical funding for the Ontario Science Centre’s community access programs, including Adopt-a-Class, an initiative that ensures students from underserved neighbourhoods are able to visit the Centre. By providing early access to science-based learning, the Ontario Science Centre works to inspire a lifelong journey of curiosity, discovery and action for a better future.
LifeLabs Sponsors Pediatric Oncology Group
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enowned business school HEC Montreal has created its first-ever industrial research chair, with the financial support of the Natural Sciences and Engineering Research Council of Canada (NSERC). The NSERC-Prompt Industrial Research Chair in User Experience will be headed up by professors Pierre-Majorique Léger, Chairholder and Co-Director of the Tech3Lab at HEC Montréal, and Marc Fredette, Full Professor in the Department of Decision Sciences. Six major firms – D-Box, Deloitte, Desjardins Group, JDA Software, Sobey’s and Vidéotron - will serve as Chair partners and help underwrite the research, which will eventually be used to help them optimize their customers’ user experience. The six partner firms will be working closely with the research team organized by professors Léger and Fredette, The six partner firms will be by providing real-life issues for working closely with the research the experts to use in accelerating team organized by professors and enriching user experience Léger and Fredette, by providing measures, while providing the real-life issues for the experts to companies with advanced, use in accelerating and enriching customized expertise. user experience measures, while The tests done on interfaces providing the companies with of all kinds, websites and advanced, customized expertise. mobile applications, will allow the researchers to analyze users’ emotional and cognitive response. The partners will be providing their platforms and their unique relationships with their customers, in return for which the researchers will furnish them with research and analysis tools reflecting the latest scientific advances in this field.
LifeLabs has announced a partnership with the Pediatric Oncology Group of Ontario (POGO) as lead sponsor of the Pajamas and Pancakes program. To mark the occasion, LifeLabs employees flipped pancakes and shared a pancake breakfast in their LifeLabs pajamas to raise funds and awareness in support of POGO. LifeLabs will be donating $200,000 over four years to POGO, in addition to the funds raised at the Pajamas and Pancake breakfast. Proceeds from the event will go directly to POGO’s mission to increase access to state-of-the-art cancer care for children and families in Ontario, support education and research initiatives and provide financial support for children and families battling cancer.
Government Supports Climate Change Research in the Arctic
The Canadian government has announced it will be committing up to $1.6 million in funding to support research in Canada’s high Arctic. This funding will allow Canadian university scientists to carry out uninterrupted research operations and data collection at the Polar Environment Atmospheric Research Laboratory (PEARL), until fall 2019. Support for PEARL contributes to Environment and Climate Change Canada’s leading-edge monitoring and research in the Arctic, related to air quality, the ozone layer, and climate change. With the Arctic heating up twice as fast as the rest of the world, understanding this region is more important than ever.
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Worldwide NEWS
Canadian Patent Office to Grant MilliporeSigma’s Patent Application for CRISPR Technology
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illiporeSigma announced in late October that the Canadian Patent Office has issued a “Notice of Allowance” for MilliporeSigma’s patent application covering the company’s CRISPR technology used in a genomic-integration method for eukaryotic cells. “Our patent portfolio continues to grow worldwide, extending protection for our unique CRISPR technology as we work with the global scientific community to find new treatments for diseases,” says Udit Batra, CEO, MilliporeSigma. “This decision by the Canadian Patent Office is an important acknowledgement of MilliporeSigma’s role in advancing genome editing.” MilliporeSigma also has patent filings for its insertion CRISPR method in the U.S., Brazil, China, India, Israel, Japan, Singapore, and South Korea. The forthcoming Canadian patent, entitled “CRISPR-BASED GENOME MODIFICATION AND REGULATION,” covers chromosomal integration, or cutting of the chromosomal sequence of eukaryotic cells (such as mammalian and plant cells) and insertion of an external or donor DNA sequence into those cells using CRISPR. Scientists can replace a disease-associated mutation with a beneficial or functional sequence, a method important for creating disease models and gene therapy. Additionally, scientists can use the method to insert transgenes that label endogenous proteins for visual tracking within cells. Once formally granted, the Canadian patent will extend the protection of MilliporeSigma’s CRISPR integration technology into North America for the first time, further strengthening the company’s patent portfolio. The Australian Patent Office granted MilliporeSigma its first CRISPR patent in June of 2017, followed by the grant of a European patent in September of 2017. CRISPR genome-editing technology, which allows the precise modification of chromosomes in living cells, is advancing treatment options for some of the toughest medical conditions faced today. CRISPR applications are far-ranging — from identifying genes associated with cancer and rare diseases to reversing mutations that cause blindness. With a 12-year history in the genome-editing field, MilliporeSigma was the first company to offer custom biomolecules for genome editing globally (TargeTron RNA-guided group II introns and CompoZr zinc finger nucleases), driving adoption of these techniques by researchers all over the world. MilliporeSigma was also the first company to manufacture arrayed CRISPR libraries covering the entire human genome, accelerating cures for diseases by allowing scientists to explore more questions about root causes. In May 2017, MilliporeSigma announced its alternative CRISPR genomeediting method, called proxy-CRISPR.
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September/October 2017 Lab Business
Scouting Tool to Enable Open Innovation for Universities
IN-PART announced the launch of a new scouting service for R&D professionals, called IN-PART: Discover. The new service will provide companies with opportunities for collaboration, specific to their requirements. In recent years, there has been increasing interest in open innovation, particularly as universities are becoming more aware of, and open to, the benefits of collaborating with industry. The IN-PART matchmaking platform features an intuitive algorithm to smart-match companies with the best and most relevant commercially ready research from 96 university clients.
Strategic Alliance Formed for R&D of Pharmaceutical Cannabis Products
Shimadzu Scientific Instruments (SSI) has signed a Memorandum of Understanding (MOU) with Cure Pharmaceutical Corp and CK Sciences. This collaborative agreement will focus on researching and developing safer pharmaceutical cannabisbased products and moving these products through clinical trials using FDA guidelines. Shimadzu, Cure Pharmaceutical Corp and CK Sciences will be researching and profiling the synergistic effects of the cannabinoids and terpenes. Cure/CK Sciences will utilize SSI instruments to generate data to validate cannabis as a viable pharmaceutical treatment.
Sartorius Stedim Biotech Awarded for Leadership in Bioanalytical Contract Testing
Sartorius Stedim Biotech (SSB) received Frost & Sullivan’s 2017 European Customer Service Leadership Award for Bioanalytical Contract Testing Services. This award recognizes the unique product and service combination and enhanced customer satisfaction provided by Sartorius Stedim BioOutsource, SSB’s subsidiary based in Glasgow. Sartorius Stedim BioOutsource navigates biopharmaceutical manufacturers through the complexities of the drug development cycle and enables them to make informed data-driven decisions. The Contract Testing Organization offers a broad portfolio of bioanalytical services and offthe-shelf bioassays.
By David Suzuki with contributions from Ian Hanington
CO2 and food:
We can’t sacrifice quality for quantity
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Dr. David Suzuki is a scientist, broadcaster, author, and co-founder of the David Suzuki Foundation. Ian Hanington is Senior Editor, David Suzuki Foundation. Learn more at www.davidsuzuki.org.
igger isn’t always better. Too much of a good thing can be bad. Many antienvironmentalists throw these simple truths to the wind, along with caution. You can see it in the deceitful realm of climate change denial. It’s difficult to keep up with the constantly shifting – and debunked – denier arguments, but one common thread promoted by the likes of the Heartland Institute in the U.S. and its Canadian affiliate, the misnamed International Climate Science Coalition, illustrates the point. They claim carbon dioxide is good for plants, and plants are good for people, so we should aim to pump even more CO2 into the atmosphere than we already are. We’ve examined the logical failings of this argument before – noting that studies have found not all plants benefit from increased CO2 and that most plants don’t fare well under climate changeexacerbated drought or flooding, among other facts. Emerging research should put the false notion to rest for good. Several studies have found that, even when increased CO2 makes plants grow bigger and faster, it reduces proteins and other nutrients and increases carbohydrates in about 95 per cent of plant species, including important food crops such as barley, rice, wheat and potatoes. A 2014 Harvard School of Public Health study, published in Nature, found that increased CO2 reduced the amount of valuable minerals such as zinc and iron in all of them. Another study, by Irakli Loladze at the Catholic University of Daegu in South Korea, looked at 130 species of food plants and found increased CO2 caused calcium, magnesium, potassium, zinc and iron concentrations in plants to decline by an average of eight per cent, while sugar and starch content increased.
As a Scientific American article points out, billions of people depend on crops like wheat and rice for iron and zinc. Zinc deficiency is linked to hundreds of thousands of deaths, mostly children, and exacerbates health issues such as pneumonia and malaria. Iron deficiency, which causes anemia, is responsible for one-fifth of maternal deaths worldwide. Part of the problem with the industrial agricultural mindset and the denier argument that CO2 is plant food or “aerial fertilizer” is the idea that bigger and faster are better. These studies illustrate the problem with the climate changedenial argument but, in its pursuit of profit, industrial agriculture has often made the same mistake. Plants – and now even animals like salmon – have mainly been bred, through conventional breeding and genetic engineering, to grow faster and bigger, with little regard for nutrient value (leaving aside anomalies like the not-entirelysuccessful “golden rice”). But higher yields have often resulted in less nutritious fruits and vegetables. Genetic engineering’s promise was increased yields and reduced need for pesticides, but studies show it has fallen far short of that ambition. A 2016 National Academy of Sciences study, as well as a New York Times investigation, found no evidence that genetically engineered crops increased yields over conventional crops. Although insecticide and fungicide use on GE crops in the U.S. and Canada has decreased, herbicide use has gone up to the point that overall pesticide use has increased. France, which doesn’t rely on genetically modified crops, has reduced use of all pesticides – 65 per cent for insecticides and fungicides and 36 per cent for herbicides – without any decrease in yields. The “golden rice” experiment shows that plants can be engineered for higher nutrient value, but that hasn’t been the priority for large agrochemical companies. As for carbon dioxide, we know that fossil fuel use, industrial agriculture, cement production and destruction of carbon sinks like wetlands and forests are driving recent global warming, to the detriment of humanity. The one flimsy argument climate change deniers have been holding onto – that it will make plants grow faster and bigger – has proven to be a poor one. Like life itself, science is complex. Reductive strategies that look at phenomena and reactions in isolation miss the big picture. Our species faces an existential crisis. Overcoming it will require greater wisdom and knowledge and a better understanding of nature’s interconnectedness. Tackling climate disruption and feeding humanity are connected. It’s past time to ignore the deniers, reassess our priorities and take the necessary measures to slow global warming. LB
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Lab PROFILE
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September/October 2017 Lab Business
Lab PROFILE
Feeling
lucky story by
Hermione Wilson
Slot machines and brain scans bring new insights at UBC’s Centre for Gambling Research
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Lab PROFILE
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Dr. Luke Clark, Director at the Centre for Gambling Research in British Columbia
Ontario, Alberta and Quebec are all very strong in the gambling field, pretty much worldleading, but BC hadn’t had much research in the area at all. The decision to create the centre was to try to establish that. – Luke Clark, director, Centre for Gambling Research, British Columbia
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September/October 2017 Lab Business
efore Luke Clark was recruited to head the new Centre for Gambling Research at the University of British Columbia, the British experimental psychologist was at the University of Cambridge studying how mental illnesses affected risky decision-making and what that looked like in the brain. Clark began to focus specifically on gambling behaviour in 2005, around the time the U.K. government (England and Wales) passed new legislation surrounding gambling advertisements, online gambling and new casinos, which Clark says led to an expansion and liberalization of gambling. In 2013, the British Columbia government and the British Columbia Lottery Corporation (BCLC) decided to establish the Centre for Gambling Research at UBC’s Department of Psychology. The centre opened in 2014 with Clark as its first director. “Several other Canadian provinces have been strong in this field [gambling research] going back several decades,” Clark says. “Ontario, Alberta and Quebec are all very strong in the gambling field, pretty much world-leading, but BC hadn’t had much research in the area at all. The decision to create the centre was to try to establish that.” The mandate of the Centre for Gambling Research is twofold says Clark: understand the psychology behind the negative effects of gambling and to help shape evidence-based government policy around gambling, in BC and internationally. Clark and his team – consisting of a research assistant, four graduate students, a postdoctoral researcher, and undergraduate student volunteers – accomplish the first part of their mandate through a series of experiments that seek to recreate the conditions in which problem gambling flourishes. This has led the centre to obtain four genuine slot machines from casinos in BC for research purposes. “We do a lot of our work around slot machine gambling because we think that slot machines are the most harmful, potentially addictive form of gambling that we have in society,” Clark says. Playing the slots Having real slot machines in the lab gives the centre the ability to observe how participants –both undergraduate volunteers and community members who are regular slot machine gamblers – behave when they are engaged with the machine. However, using real slot machines as opposed to a computer simulation, as would be more common in psychology research, does have its challenges Clark says. “In most areas of psychology, when we run a psychology task on a volunteer, it’s a task that the researcher has programmed to run on a computer, and the task generates an output file so that the researcher can go back and see every single thing that happened. Our slot machines don’t generate that output file.” In order to collect data from participants in the slot machine lab, Clark and his team have to recreate the participant’s behaviour after the fact. The team uses a device that is part of a system called the BIOPAC MP150, which Clark’s lab routinely use to record the participant’s heart rate and skin conductance responses. In addition, the slot machine’s spin button is “hotwired” to send an output every time the participant makes a bet. The BIOPAC system includes a series of amplifiers and wearable portable devices that connect wirelessly. “We run everything – the behaviour as well – through the BIOPAC and that becomes the transcript of what happened in that person’s session,” Clark says. The researchers are careful not to recruit those undergoing treatment for gambling disorder for these experiments, as it could trigger a relapse. “That’s not to say that it’s an impossible thing to do,” Clark says. “Around the world, addiction researchers have learned a lot about addiction from exposing people who use drugs to their drug of choice, or at least to pictures of the drug, and measuring the response. Of course, the participant would need to know in advance what the experiment involved.” He says the centre may do similar work with problem gamblers in the future. The machine zone Another facet of the work being done at the Centre for Gambling Research is looking into what happens in the brain during gambling. This project is a continuation of one Clark was involved with in London, England, before he came to BC. “We were working
Lab PROFILE
Photo credits: Martin Dee, University of British Columbia
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Lab PROFILE
with the National Problem Gambling Clinic in central London and doing a lot of brain imaging studies with those gamblers, both with PET imaging where we could measure brain neurotransmitters like dopamine and brain opioids, and a lot of functional MRI where the gambler plays a task while they’re in the scanner,” he says. “Our participants would play a simplified gambling game, for example, while they were in the brain scanner and we could see how their brain activity was changing while they played the task.” Most recently, one of Clark’s graduate students, Spencer Murch, has been heading up a study into the state in which slot machine gamblers become immersed in the game, a state that researchers refer to as the “machine zone”. This state seems to be different from the excitement usually associated with gambling, Clark says, because slot machine gamblers seem to slip into a sort of trance. “It’s a difficult state to measure because if you just tap someone on the shoulder and ask them if they are immersed in this game, it tends to snap them out of the state, so we have to be quite subtle about how we measure it,” he says. Murch’s experiment involves placing two screens on either side of the slot machine that present the participant with some target shapes at the edges of their visual field, while they play the slot machine for 20 minutes. Participants are asked to press another button if they notice changes in those visual targets. “Players who are very immersed in the game tend to miss those things happening around the machine, and we’ve seen that this correlates closely with their levels of problem gambling symptoms as well,” Clark says. Murch published the initial results of his experiment, entitled “Measuring the slot machine zone with attentional dual tasks and respiratory sinus arrhythmia” in Psychology of Addictive Behaviors in 2017, and has been awarded the Stanley Coren Prize from the UBC Department of Psychology for the best MA thesis, based on this work. The centre was recently given another opportunity to observe gambling behaviour, looking at data provided by the BCLC from its online gambling site, PlayNow.com. “We have de-identified bet-by-bet data from thousands of customers on the PlayNow website,” Clark says. “We’re looking for markers of excessive gambling in those gamblers.” Leading the way Having only opened in 2014, the Centre for Gambling Research is still quite young as far as labs go, but Clark is already thinking about the second half of the centre’s mandate and how the work might influence government policy around gambling. At present, a lot of the focus of government policy has been on responsible gambling, he says. Information aimed at increasing gamblers’ awareness about whether they may have a gambling problem and encouraging them to stick to limits when they play is often presented via posters and information booths at the casinos. But this kind of static information, says Clark, is not going to be very effective in reaching a slot machine gambler who is immersed in the machine zone. “We need active, dynamic messages, and ways of bringing a gambler’s attention to that kind of information while they’re playing and while they may be in that immersed state,” Clark says. The work being done at the centre may also have a broader relevance to addiction research, Clark admits, especially the work being done around brain imaging. One study Clark’s team conducted (the results of which were published this year), involved showing people with gambling problems images associated with slot machine play. “When we show gamblers images of slot machine play during a brain scan, those images elicit cravings and they also elicit a lot of brain activity in an area called the insula,” he says. “It’s quite a mysterious part of the brain and it’s an area that’s been implicated time and time again in addictions, but we see a very close relationship between the actual levels of cravings that problem gamblers experience and insula activity.” Perhaps, Clark muses, if a treatment can be developed to reduce this insula activity, it may work to lessen these types of cravings associated with addiction. Gambling research in BC is in its early days yet, but Clark clearly believes it is fertile ground for discovery. “One of the things I like as a scientist about working in this area is that it’s a very new field, it’s very young, and there is this quite pressing need for research and evidence to guide government gambling policy.” LB
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September/October 2017 Lab Business
Lab PROFILE
Photo credit: Gabriel Brooks
When we show gamblers images of slot machine play during a brain scan, those images elicit cravings and they also elicit a lot of brain activity in an area called the insula... it’s an area that’s been implicated time and time again in addictions. It’s quite a mysterious part of the brain and it’s an area that’s been implicated time and time again in addictions, but we see a very close relationship between the actual levels of cravings that problem gamblers experience and insula activity. – Luke Clark, director, Centre for Gambling Research, British Columbia
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Ultra-Fast Drug Screening for Forensic Research How a leading laboratory at the Institute of Forensic Medicine, University of Freiburg uses the Toxtyper LC-MSn solution to propel drug screening research and services story by
Rohan Thakur
Dr. Volker Auwärter, Institute of Forensic Medicine, University of Freiburg
I
nvestigations into the use of drugs or drugs of abuse (DOA) are dictated by the nature of the individual case. Usually, the possible drugs involved are shortlisted for screening by analysts and specific, dedicated testing methods are implemented to elucidate the drug involved. The analytical process also depends on the source of the sample. For example, the type of analyte to be detected is usually pre-determined in samples arriving from police institutions – pre-tests in urine have usually been conducted so analysts have a broad idea of the class of drug in question. In these cases, a laboratory only needs to screen for a small number of analytes. However, the event of an intoxication case, the drug responsible is less clear, so broad screening methods are required. In these cases, the samples available for analysis will vary, and range from blood, urine, hair, vitreous humor and occasionally, organs. Liquid chromatography mass spectrometry (LC-MS) and gas chromatography mass spectrometry (GC-MS) are used to analyze drugs and DOA in biological matrices. When analyzing body fluids, however, LC-MS has become the key method of choice. An automated LC-MSn approach has been developed for the detection of drugs and DOA in a range of biological samples, as well as for the constant monitoring of the new psychoactive substance (NPS) market. The Institute of Forensic Medicine, University of Freiburg, uses novel broad screening methods to screen for vast arrays of analytes in biological samples, and develops innovative approaches to tackle forensic toxicological problems. A forensic case study – Professor Dr. Auwärter’s laboratory Professor Dr. Volker Auwärter’s laboratory at the Institute of Forensic Medicine, University of Freiburg, benefits from specifically developed toxicological solutions, to further research and services in forensics. The laboratory runs drug screening services for organizations across Europe, in Luxembourg, Belgium and Poland, for example. The institute also co-operates with a laboratory in the U.S., where it contributes to method development. As an academic laboratory, the key priorities of the
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Application NOTE
Institute’s work lie in research and analytical services, often for requests dealing with legal cases. The role of the Institute is to conduct toxicological analysis on cases where drugs or drugs of abuse (DOA) are involved. This primarily involves testing blood, urine and hair samples and in post-mortem cases, stomach contents, vitreous humor and occasionally organs such as liver, kidney, and muscle tissue. In some instances, analysis of powders, liquids, paper or other materials is also requested. Due to the nature of samples analyzed, semi- or broad-targeted approaches are needed to screen for a vast array of analytes. The source of the samples sent to the laboratory varies, and has changed over time. “In the beginning, death cases and services for investigative authorities were the main source of work for us as a forensic laboratory,” explains Auwärter. “Over time, we have received more samples from the police, taken from offenders under the influence. Then it developed further and we now have more clinical samples, for example from prisons and forensic psychiatric clinics. Now this represents the larger portion of our work.” Currently, the Institute receives approximately 11,000 cases to analyze per year, ranging from simple blood alcohol analysis to full post-mortem toxicology. Due to the Institute’s focus on research, the majority of funding received by the laboratory is for this purpose. “The laboratory stands on two legs: one is academic, where we have funding for teaching and research, and the other is the service we provide to private facilities and investigative authorities,” says Auwärter. “The two elements support each other – if we’re good in research, we can offer new, specialized methods to our customers, and if we provide a good service, this generates revenue to channel into innovative research. We’re not a high-throughput laboratory, so we always have to keep on top of the latest developments in order to offer specialized services private laboratories with highthroughput machines are not able to provide.”
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The LC-MS laboratory at the Institute of Forensic Medicine, University of Freiburg.
Application NOTE
Currently, the Institute receives approximately 11,000 cases to analyze per year, ranging from simple blood alcohol analysis to full postmortem toxicology.
Dedicated projects The Institute has conducted EU-funded projects since 2011, all of which maintain a core focus on drugs market monitoring and development of methods to detect NPS in biological matrices. The laboratory must apply for new funding every two years, and over time the nature of the project has changed depending on the EU commission’s goals. “We have to assess what the EU commission wants, and which project would fit in with our purpose,” explains Auwärter. “Previously, we have applied for a security research project, as well as the Drug Information and Prevention Program – you always have to look out for those which fit, and often need to adapt to them. In the beginning, the projects were more constructed around questions of prevention, whereas now, the projects are covered more by the criminal investigation area. At the moment, together with the Federal Criminal Police Office, we’re contributing to some profiling work to see which kinds of impurities are found in drugs, to learn about their routes of synthesis.” As specialists in NPS detection, the demand for this service from the Institute has been high, so the research effort to keep up to speed with rapid developments in identification of new compounds in NPS is huge. In 2008, the problem of detection of the NPS ‘Spice’ became a widespread and common occurrence which swept across the industry and as a result, a large proportion of the laboratory’s work is involved with detecting synthetic cannabinoids. Since 2012, screening for NPS has become an issue even in standard cases, and is a constant factor in the laboratory’s work: “Every death case we complete will undergo the whole spectrum of NPS screening,” adds Auwärter, “although this is a huge public health concern, it is good for us as the demand for our specialist services has risen.” The laboratory uses the Toxtyper (Bruker Daltonik) LC-MSn-based library solution in the EU monitoring projects: drug samples are purchased online by the laboratory to be analyzed for the principle active compounds. The instrument quickly
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Application NOTE
The robustness, quality of data and ease of use of this instrument have simplified and accelerated the mass spectrometry screening capabilities in the laboratory, shortening the overall turnaround time of a case.
identifies these samples and where drugs have already been screened before; it is used to identify specific groups of drugs, for example synthetic cannabinoids, and simultaneously looks for unknown compound spectra. These compounds can then be selected, purified and then have their structures analyzed with other instruments. The robustness, quality of data and ease of use of this instrument have simplified and accelerated the mass spectrometry screening capabilities in the laboratory, shortening the overall turnaround time of a case. By reducing the time spent on routine sample analysis, more time can be spent on complex intoxication or post-mortem cases, which is very valuable. Reduced sample preparation time is one of the key advantages of using such a technique: the time taken to prepare samples for GC-MS is up to one hour, whereas this unique LC-MS solution takes approximately 10 minutes.
Moving forward The rapidly expanding and evolving designer drug testing arena is unlikely to slow down in the near future. Therefore, laboratories such as that of the Institute of Forensic Medicine will increasingly need to rely on vendors for their innovative, tailored technologies which are specifically designed with these research challenges in mind. The commitment of such vendors to provide the state-of-the-art instrumentation and industry expertise required for progressive toxicological research to take place paves the way for future discoveries. The reciprocal collaboration seen in this case study enabled the co-development of novel drug screening methods, which propels the Institute’s research and service contributions to the forensic and toxicology industry. For more information, visit www. bruker.com/products/mass-spectrometry-and-separations/lc-ms/ion-trap/ toxtyper/overview.html. For more information about the Institute of Forensic Medicine, visit www.uniklinik-freiburg. de/rechtsmedizin.html. LB Rohan Thakur, Executive Vice President at Bruker Daltonics, has over 20 years of experience in mass spectrometry, including 14 years in MS development and has several patents in the field of ion optics. During his career he held positions as Director Global Marketing for mass spectrometry solutions at Thermo and was Director of Drug Discovery at a Pharma CRO for two years before joining Bruker. Dr. Thakur received his PhD in Chemistry from Kansas State University and did post-doctoral studies at Rutgers University, where his work involved using high-resolution MS analysis to prove the formation of ring-opened benzene metabolite-DNA and protein adducts.
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Lab WARE
Integrating Flexibility and Scalability with New Fraction Collector
Bio-Rad has introduced a new NGCTM Fraction Collector paired with the NGCTM Chromatography System, which supports protein purification across all stages of drug discovery and development, and small-scale batch production on one hardware and software platform. Mix and match racks accommodate all collection needs. These high-capacity flexible rack options enable fractions from millilitres to litres, all freely accessible during a purification run. No need to run in a refrigerator, optional Peltier cooling enables fractions to remain cool conveniently on the benchtop. www.bio-rad.com/FractionCollector
Faster, More Reproducible Dry Powder Inhaler Testing with Critical Flow Controller
Copley Scientific has launched Critical Flow Controller TPK 2100 for the testing of dry powder inhalers (DPIs). A new “fly-by-wire� flow control valve allows operation to be automated so data generation is more efficient and reproducible. Inhaler pressure drop, P1, and test flow rate are accurately and rapidly set by the TPK 2100 during test set-up, whilst in-line flow measurement can be accommodated and in-situ impactor leak testing is fully automated for the first time. The user is warned if the important P3/P2 ratio is greater than 0.5, giving full confidence that tests are conducted under sonic flow conditions. Data output to printer and computer are standard, with enhanced monitoring and reporting of critical in-test parameters. The new instrument allows users to emulate the previous generations of TPK, promoting interchangeability and integration into existing standard operating procedures. www.copleyscientific.com
New Gasket and Braided Hose Range Offer Confident Fluid Path Validation
Wireless Temperature Monitoring Kit Enables Remote Monitoring of UltraLow Storage Units
The new Accsense WiFi Ultra-Low Temperature Monitoring Starter Kit is a wireless device to monitor low temperatures in Ultra-Low Freezers and Liquid Nitrogen (LN2) tanks. View temperature data online in realtime via web browser, receive alarms via email, cell phone, pager, or landline. It includes power/internet outage notifications, download data for offline analysis, and secure system with automatic data backups. Accsense wireless remote monitoring systems continuously monitor and record temperature, send alarm notifications on temperature excursions or power outages, and document historical data for proof of best practices. The kit includes: A2-05W WiFi Sensor Pod, E1-21 Temperature Probe, and E1-34 Nylon Temperature Buffer. Accsense Monitoring is ideal for temperature measurement and notification in a wide temperature range and for proving best practices. www.dataloggerinc.com/product/wifiultra-low-temperature-monitoringstarter-kit
BioPure has innovated a range of high purity platinum-cured silicone gaskets and platinumcured silicone braided hoses. This technology is designed to meet the exacting requirements of biotechnology and pharmaceutical single-use applications, enabling users to simplify and expedite validation procedures. The gaskets are designed for bioprocessing applications where fluid path connections are needed. They are designed in accordance with ASME-BPE standards and are ISO14644 Class 7 cleanroom manufactured and packed. The single and double-braided flexible hoses are designed for high pressure applications. They offer excellent bend radius, while a continuously extruded silicone bore assures the integrity of the contacting fluid. The new hoses are also able to withstand repeated autoclave and sterilisation processes. www.wmftg.com
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Lab WARE Mass Comparators Create Efficient, Error-Free and Traceable Calibration
XPR mass comparators are helping labs and industrial clients provide intuitive, efficient and secure weight calibration processes at higher throughput. XPR’s sensitive, worry-free mass determination is assured by a range of Mettler Toledo features that enhance both accuracy and processing speed. LevelMatic reduces corner-load effects to an absolute minimum. MC Link calibration software offers flexible calibration process configuration, on-screen user guidance, automatic calculations and comprehensive data handling for easier, faster processes. MC Link also manages measurement uncertainty. All process information and calibration data are stored securely in a central database to fulfill your highest process-security requirements. The addition of StatusLight means operators never weigh when the comparator is out-of-calibration or off-level. A built-in indicator registers green when it is safe to calibrate, yellow when an issue needs attention, and red when a particular test is outdated. www.mt.com/ca/en/home/products/Laboratory_Weighing_Solutions/Mass_Comparators/Manual_ Comparators.html
Anti-A and Anti-B Chromatography Resins Introduced for Enhancement of Plasma-Derived Immunoglobulin
MilliporeSigma recently launched Eshmuno P anti-A and Eshmuno P anti-B affinity chromatography resins specifically designed to remove anti-A and anti-B isoagglutinin antibodies during the manufacturing of plasma-derived immunoglobulin (Ig) therapies. Introduction of chromatographic steps using Eshmuno P resins to specifically deplete anti-A and anti-B antibodies is expected to reduce patient risk for adverse medical events associated with plasma-derived Ig therapies. This enhanced patient safety is achieved without negatively impacting process economics by reusing the resins for at least 200 cycles, with acid or alkaline cleaning, without loss of performance. Eshmuno P anti-A and Eshmuno P anti-B resins are manufactured using a combination of MilliporeSigma’s proprietary base matrix technology and a novel synthetic approach. The resins are released by an innovative test method to evaluate performance with significantly less variability compared with classical agglutination methods. www.emdmillipore.com/EshmunoP
New Bake Plate Designed for Precise Heating of Small Silicon Wafers
Torrey Pines Scientific, Inc. recently announced its new WaferPlate Programmable Bake Plate with uniform heating across the surface of better than 1 per cent over a heating range from room temperature to 350 C. It is ideal for precisely heating 304.8mm and smaller silicon wafers, electronic chips, displays, adhesives, and for doing photo-resists and more. The WaferPlate Model HP90 has a large circular 352.4 mm milled-flat plate aluminum surface with temperature uniformity better than 1 per cent across the centre. The unit is controllable remotely from a PC or industrial controller via the RS232 I/O port using the command set provided. Also provided is a bench top controller which is fully programmable holding five routines of 10 steps each in memory for instant and repeatable recall and use. www.torreypinesscientific.com
Precision Engineered Gaskets Provide Stability in SIP Cycles
FlowSmart precision-engineered PolyClamp EPDM gaskets retain their geometric stability even after repeat steam-in-place (SIP) cycles. Formulated for SIP stability in the biotechnology and pharmaceutical industries, FlowSmart’s functionality ensures that the gaskets do not compromise critical high-purity processes and do not trap bacteria. FlowSmart’s PolyClamp gaskets overcome the issue of stickiness, which can be problematic when using EPDM gaskets after a number of SIP cycles have been performed, as the gasket can adhere to the ferrule faces. FlowSmart’s EPDM material ensures clean, intact removal with no trace of the elastomer material finding its way into the process fluid. Designed in accordance with ASME-BPE standards, PolyClamp EPDM gaskets are USP Class VI certified and are available in 10 size options. www.wmftg.com
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LIST OF ADVERTISERS & WEBSITES Bio-Rad
Page 2 ....................................................www.bio-rad.com/zoe
VWR
Page 4 ....................................................................www.vwr.com
CANADIAN FOOD BUSINESS
Page 16 ........................... www.canadianfoodbusiness.com
HANNA
Page 24 .................................................... www.hannacan.com
Moments in time
The
Antipsychotic Receptor
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n 1975, Philip Seeman discovered that the effectiveness of antipsychotic drugs was directly related to their ability to block the dopamine D2 receptor in the brain. In 1963, Seeman began his search for a receptor in the brain that might be the target for all antipsychotic drugs, thinking this target might be deranged in schizophrenia. Seeman eventually realized that he needed radioactive haloperidol containing tritium atoms at high concentration in order to identify the receptor for haloperidol in brain tissue. Haloperidol is a typical antipsychotic medication used to treat schizophrenia, Tourette syndrome and bipolar disorder. Seeman found that all known antipsychotics inhibited the binding of radioactive haloperidol at concentrations that correlated to, and predicted, the antipsychotic clinical daily doses in schizophrenia patients. The so-called antipsychotic receptor was renamed the dopamine type 2 or D2 receptor, which was later found to be overactive in schizophrenia. In addition to being the common target for antipsychotic drugs, the D2 receptor also serves as the main target for dopamine-like drugs that alleviate Parkinson’s disease.
Sources: www.camh.ca/en/research/about_research_at_CAMH/milestones_and_history/Pages/Milestones-and-History.aspx www.scholarpedia.org/article/Dopamine_and_schizophrenia www.ncbi.nlm.nih.gov/pubmed/16848689 www.ncbi.nlm.nih.gov/pubmed/11171942
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