Laboratory Focus March 2012

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AutoGenomics Revolutionizing Molecular Testing Page 12

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

$30M gift propels stem cell therapies and one-stop patient care at McMaster this world class university,” said Les Boris, on behalf of his parents’ Marta and Owen Boris Foundation. His sister Jackie Work added: “The Michael G. DeGroote School of Medicine is ranked among the top 20 medical schools in the world. This is the best place to commit to the future.”

The Marta and Owen Boris Foundation was established by Marta and Owen Boris who created the Hamilton cable company Mountain Cablevision and developed it over 50 years before selling it to Shaw Communications in 2009. Owen Boris died in April, 2011.

“McMaster has been renewing its commitment to our community, and to have community members make such a significant contribution to the University is truly outstanding,” said Patrick Deane, president of McMaster.

“Great research, great discoveries, and better patient care. The Boris family gift will accelerate our ability to make great things happen.”

Dr. John Kelton, dean and vice-president of the Faculty of

Jackie Work and Les Boris

A Hamilton family is giving McMaster University $30 million to accelerate the university’s development of stem cell therapies.

Of the total, $24 million will be used to establish the Boris Family Centre in Human Stem Cell Therapies, which will speed the commercial development of discoveries made at the McMaster Stem Cell and Cancer Research Institute. The six-year-old institute has had several major breakthroughs, including the ability to turn human skin into blood.

The funds will also establish two senior research chairs, one in blood stem cells and the other in neuro stem cells; set up several fellowships and technician positions; build the facility and provide a fund for emerging opportunities.

The other $6 million is for a unique clinic that will allow patients with complex health problems to see several specialists and have related tests during one visit.

“McMaster University has proven its ability to fast forward discoveries from the lab bench to the patients’ bedside, it made perfect sense to make this investment in

Health Sciences, added: “This is an innovative and action-oriented family. They understand the great potential McMaster has to make medical breakthroughs, and their willingness to place their bets on McMaster is a tremendous vote of confidence in us.”

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Mick Bhatia, scientific director of the McMaster Stem Cell and Cancer Research Institute added: “In a short time we’ve become world renowned for our human stem cell discoveries. Now is the time to move these discoveries to the patient.”

2

March 2012 Laboratory Focus www.bioscienceworld.ca

news Canadian Isotope project enters final stretch A research project exploring the potential for making medical isotopes with X-rays from a particle accelerator instead of a nuclear reactor is about to move to the large scale.

The Canadian Isotope Project, led by the Canadian Light Source (CLS) and partners in-

cluding the National Research Council of Canada, and medical researchers in Winnipeg, Ottawa and Toronto, is set to scale-up their work to production levels with the delivery of a new particle accelerator built by Ontario-based Mevex Corporation.

“We are very excited to be passing this key milestone in the project,” said Mark de Jong, CLS director of Accelerators and project leader. “We have made a lot of progress over the last year in terms of the project’s theoretical work, refining different pieces of the

process and moving construction and design of our test bed forward. With the delivery of this full-scale accelerator we can now move to demonstrate what we set out to do – produce medical isotopes safely, reliably and affordably.”

Continued from page 3

PUBLISHER/EDITOR-IN-CHIEF Terri Pavelic staff writer Shawn Lawrence CONTRIBUTING WRITERS Dannis Fafard Guobin Ma NATIONAL ACCOUNT MANAGER Marcello Sukhdeo GRAPHIC DESIGNER Elena Pankova CONTROLLER John R. Jones MARKETING MANAGER Mary Malofy CIRCULATION DIRECTOR James Watson 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 6 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.

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www.bioscienceworld.ca Laboratory Focus

Mark de Jong

continued from page 2

The Canadian Isotope Project uses a particle accelerator to bombard a target made of molybdenum-100 metal with high-energy X-rays. The X-rays knock a neutron out of the nuclei of some of the molybdenum-100 atoms in the target, converting them to the isotope molybdenum-99.

After being chemically separated from the target, the molybdenum-99 will be shipped to hospitals where it decays into technetium-99m and is injected into patients for diagnosing heart conditions.

Two or three accelerator systems like the one now being installed at the CLS could supply all of Canada’s needs for technetium-99m.

Researchers at the NRC in Ottawa have been performing theoretical modeling of key aspects of the production process and producing small quantities of medical isotope using the same process as will be used at the CLS with a smaller particle accelerator. Isotopes produced by the full-scale facility at the CLS will be chemically separated from the metal target by scientists at Health Sciences Centre (HSC) Winnipeg and assessed by doctors at the University of Ottawa Heart Institute and University Health Network in Toronto.

The Canadian Isotope Project was one of four projects funded by the Government of Canada’s Non-nuclear reactor Isotope Supply Programme (NISP). The CLS-led project received $10 million from NISP with an additional $2 million from the Province of Saskatchewan. NISP was established to fund research into ways to produce medical isotopes without using a nuclear reactor in the wake of shortages caused by difficulties with Canada’s NRU research reactor.

The NISP projects are all working to produce the most used medical isotope, technetium-99m, which is used in approximately 5,500 medical scans daily in Canada.

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March 2012

news

fIGhT AGAInsT neGlecTed GloBAl dIseAses Moves AnoTheR sTeP foRwARd One year after The Centre for Drug Research and Development (CDRD) and the Neglected Global Diseases Initiative at the University of British Columbia (NGDI-UBC) came together to develop interventions for neglected global diseases, a project to combine existing approved drugs to better treat Tuberculosis (TB) has emerged as the collaboration’s leading prospect.

TB is the second leading cause of death by infectious disease in adults worldwide and it is estimated that one third of the world’s population is infected with Mycobacterium tuberculosis (Mtb).

Research by UBC’s Drs. Santiago Ramón-García and Charles Thompson has found a synergistic combination of two known drugs (used for other therapeutic applications but never before to treat TB) capable of inhibiting Mtb growth, while neither of these drugs have any effect on their own against Mtb. “Although this partnership

is still relatively young, it is already proving to be very valuable in this global fight,” said Dr. Kishor M. Wasan, director and co-founder, NGDI-UBC and professor and associate dean, Research and Graduate Studies, Faculty of Pharmaceutical Sciences, UBC. The partnership brings together CDRD’s drug development platform and commercialization know-how with NGDI-UBC’s extensive network of expertise that extends across broad disciplinary boundaries. This part-

nership thereby augments each organization’s ongoing drug development efforts in partnership with world leading scientists, all with a mind to ensuring reasonable, fair and affordable access for developing countries.

In collaboration with CDRD’s screening division, Drs. Ramón-García and Thompson introduced the concept of “2+2=16” in TB drug development. They identified 14 combinations of known drugs that acted in synergy when inhibiting Mtb growth in

Professor Shana Kelley

Mycobacterium tuberculosis bacteria.

Photo: Janice haney Carr

vitro and within macrophages.

These were then further analyzed to identify combinations with suitable pharmacokinetic properties. One of them has now been chosen as the lead combination to be taken forward into in vivo proof of concept studies.

“Collaborating with CDRD has provided us with access to a new array of drug development infrastructure and expertise,” said Dr. RamónGarcía. “It has also brought new funding to our research through the CDRD-Pfizer Innovation Fund. Through CDRD, we now have one of the world’s top pharmaceutical companies behind us as a key partner.”

“This project is really just the beginning for the CDRD-NGDI partnership,” said Karimah Es Sabar, senior vice president, Business and Strategic Affairs, CDRD. “We have several additional highly-promising projects in the pipeline focused on developing therapies for some of the world’s most devastating illnesses, and we know that more exciting news will soon follow.”

GenoMe Canada laUnChes fUndinG CoMpetition in personaliZed MediCine In partnership with the Canadian Institutes of Health Research (CIHR), Genome Canada says it is seeking proposals for large-scale research projects focusing on the application of genomics in the area of personalized health.

Up to $67.5 million is available for the competition, with the federal government providing $40 million through

Genome Canada and up to $22.5 million through Canadian Institutes of Health Research (CIHR). An additional $5 million is available from the Cancer Stem Cell Consortium (CSCC). To qualify for funding, researchers must obtain matching funding that is at least equal to that provided through the competition.

Matching funding is typi-

cally derived from provincial, academic, private sector or international sources.

To be eligible, proposals must include genomics approaches as essential components in terms of importance to the overall outcomes of the project; address personalized health in humans; and be of a scale and scope such that they are able to address chal-

lenges requiring a genomics approach, be internationally competitive and have the potential for major impact.

The application process has already begun, and decisions will be announced by the end of the year. More information is available at www.genomecanada.ca/en/ portfolio/research/2012-competition.aspx.

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March 2012 Laboratory Focus www.bioscienceworld.ca

news

GRAnd chAllenGes cAnAdA Announces second Round of GRAnTs

Dr. Walter Karlen

Dr.Karim Damji

Grand Challenges Canada has announced its second round of Rising Stars in Global Health grants. In all, 15 grants valued in total at more than $1.5 million were awarded to innovators from across the country in support of their work to improve global health conditions.

“When you look at the range of innovations and the potential those creative ideas have to make a difference, Canadians can’t help but be proud of our country’s contribution to the health and well-being of the international community,” said Dr. Peter A. Singer, CEO of Grand Challenges Canada.

“Bold Canadian ideas with big impact can save lives.”

The researchers were each awarded a $100,000 grant to further develop their innovations, the grantees are: • From Vancouver: Dr. Walter Karlen is developing a low-cost cell phone test to diagnose pneumonia in the developing world • From Edmonton: Dr. Aman Ullah is developing a filter

Dr. Karim S. Karim

made from chicken feathers to eliminate the deadly carcinogen, arsenic, from drinking water • Also from Edmonton: Dr. Karim Damji is developing methodologies for preventing and treating glaucoma, a major cause of blindness in poor countries • From Waterloo: Dr. Karim S. Karim is working on a device for rapid TB detection through digital imaging, a low-cost and effective diagnostic • From Toronto: Dr. Jan Andrysek is creating an inexpensive and effective artificial knee joint for disabled people in the developing world • From Montreal: Dr. Cedric Yansouni is working on a diagnostic that is cost effective and non-invasive to determine whether a patient has visceral leishmaniasis, a deadly disease • From Quebec City: Dr. David Richard is working on a lowcost vaccine for malaria, a disease that infects 216 mil-

U of a researCher disCoVers neW VaCCine aGainst hCV

Dr. Jan Andrysek

lion people a year and kills 655,000 annually.

Each grantee has created a two-minute video to explain his or her proposal. The videos can be seen at http:// www.grandchallenges.ca/ grand-challenges/gc1 stars/ canadasrisingstars/round2grantees/ The grantees were selected through a rigorous peer review process. Among the criteria the proposals needed to meet were Grand Challenges Canada’s Integrated InnovationTM approach, which shortens the path to implementation of the discovery.

Innovators must consider ethical and cultural barriers, the health systems required to deliver the discoveries and the commercialization of their solutions so that they can be distributed to the people who need them, cost-effectively.

If their ideas are effective and proven, the innovators will be eligible for an additional Grand Challenges Canada scale-up grant of $1 million.

Michael houghton

A University of Alberta researcher and Canada Excellence Research Chair in Virology has made the discovery of a vaccine that will potentially help combat hepatitis C. Michael Houghton, who led the team that discovered the hepatitis C virus in 1989, announced his findings at the Canada Excellence Research Chairs Summit in Vancouver.

Houghton, also the Li Ka Shing Chair in Virology at the University of Alberta, says the vaccine, developed from a single strain, has shown to be effective against all known strains of the virus. It took more than 10 years to develop and started while he was working for the drug com-

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pany Novartis. Following previous vaccine tests funded by the National Institutes of Health that yielded promising results, he said there remained two critical questions.

“Did the recipients actually produce antibodies that could neutralize the actual infectious virus,” he said, “and if they could, how broad was the neutralizing response?”

The challenge, Houghton said, was that hepatitis C is more virulent than HIV, thus coming up with a vaccine that would neutralize the different strains around the world was believed to be impossible.

Using a vaccine developed and tested on humans in his University of Alberta lab, Houghton and his coinvestigator John Law discovered that the vaccine was capable of eliciting broad cross-neutralizing antibodies against all the different major strains.

Houghton says that this finding bodes good news for those with hepatitis C and those who live or travel to areas where the disease is prevalent.

“This tells us that a vaccine made from a single strain can indeed neutralize all the viruses out there,” says Houghton. “It really encourages the further development of that vaccine. This is a really a big step forward for the field of HCV vaccinology.”

www.bioscienceworld.ca

The Canadian Institute for Advanced Research announces the appointment of Dr. Alan Bernstein as the Institute’s new president and CEO commencing May 1, 2012.

Most recently, Dr. Bernstein was executive director of the Global HIV Vaccine Enterprise in New York, an international alliance of researchers and funders charged with accelerating the search for an HIV vaccine. From 2000 to 2007, Dr. Bernstein served as the inaugural president of the Canadian Institutes of Health Research, Canada’s federal agency for the support of health research, where he led the transformation of health research in Canada.

Amorfix Life Sciences has appointed Lynda Covello as vice-president of Strategic Alliances. Covello is a seasoned executive with more than 20 years experience in the biotech and biopharma sector where she has acted as consultant, counsel and senior executive, and recognized as an expert in managing intellectual property and licensing technology globally.

Additionally, she is a member of the Licensing Executives Society International (LESI) where she has held many portfolios, most recently that of chair of the LESI Standard Licensing Agreements Committee. Her other roles include being a member of the National Knowledge and Intellectual Property Management Task Force in the U.S., and an instructor in its Executive IP Education programs. She is a graduate of the University of Toronto where she specialized in International Relations.

She obtained her LL.B. and LL.M. from Osgoode Hall Law School.

BC Advantage Funds announces that Robert W. Rieder has joined its board of directors. Rieder is chairman of the board of Cardiome Pharma Corp. and previously served as Cardiome’s chief executive officer from 1998 to 2009. He has extensive experience in venture capital and the operational management of life science and

Laboratory Focus March 2012

technology companies. Prior to joining Cardiome, he was vice-president at MDS Ventures Pacific Inc., the Vancouver-based affiliate of MDS Capital Corp., and has served as a director for nine public and private technology companies. Rieder has also acted as chief operating officer for DBA Telecom Inc., and CEO for Synapse Technologies Inc. He holds a MBA degree from the University of Western Ontario.

Medical diagnostic company Miraculins Inc. announces that distinguished U.S. Cardiologist Dr. Henry A. Solomon has been appointed to the PreVu Medical advisory board. Dr. Solomon received his MD from Columbia University College of Physicians and Surgeons (New York, NY), completed his internship and residency at Montefiore Hospital and Medical Centre (New York, NY), and his Cardiology Fellowship at the New York Hospital - Cornell Medical Center (New York, NY). He is a Diplomate of both the American Board of Internal Medicine and the American Board of Cardiovascular Disease. He was most recently the chief medical officer, business development, of the American College of Cardiology. He continues to serve as senior medical advisor to the American

APPoInTMenTs College of Cardiology (which publishes the prestigious, peer reviewed Journal of the American College of Cardiology), as well as Chair of the College’s Professional and Corporate Consortium.

Antonella Mancuso has been promoted to president, Global Commercial Operations and chief manufacturing officer, of Patheon. Ms. Mancuso will assume responsibility for all of Patheon’s commercial operating units in North America and Europe. In her previous role as senior vice-president and managing director European Operations, she managed the company’s commercial manufacturing operations outside of North America.

Mancuso joined Patheon in 2001 as production manager of Patheon’s facility in Monza, Italy, becoming site director in June 2002. Prior to joining Patheon, Mancuso held progressively senior roles in production and manufacturing during her six years at Bristol-Myers Squibb in Italy.

She has also worked at Select Pharma and Bioprogress.

She holds a degree in Pharmaceutical Chemistry and Technology from La Sapienza University of Rome.

John Helou has been named president of Pfizer Canada Inc. Helou, a veteran of more than 25

years in the pharmaceutical industry and head of the Pfizer Specialty Care Business Unit (SCBU) for Canada and Puerto Rico, succeeds Paul Lévesque, who has been named Chief Marketing Officer for Pfizer Primary Care in the United States. Mr. Lévesque will be moving to Pfizer headquarters in New York City to take up that position. While taking this expanded leadership position in Canada, Mr. Helou will maintain his role as head of the SCBU. He is based at the company’s Canadian headquarters office in Kirkland, QC. Helou began his career as a chemical engineer with DuPont Canada in 1980, moving five years later to the company’s pharmaceutical business where he took positions of increasing responsibility in sales, marketing, strategic planning and business development in Canada, the U.S. and at the global level.

In 1997, Helou set up and became general manager of Agouron Canada, the Canadian operations of a start-up biotech company specializing in HIV/AIDS and oncology treatments. Agouron was subsequently acquired

by Pfizer and the business operations transferred in 2003, at which time he was appointed Pfizer Canada’s director of Sales for its Specialty Business. In 2006 he

5

was named vice-president, Public Affairs and Stakeholder Relations, before being named head of the SCBU when it was formed in 2009.

MethylGene Inc. has appointmented Dr. Henry J. Fuchs to its board of directors. Dr. Fuchs is currently executive vice-president and chief medical officer of BioMarin Pharmaceutical Inc. From 2005 to 2009, he was executive vice-president and chief medical officer of Onyx Pharmaceuticals, overseeing expanded development of the kinase inhibitor Nexavar and other key development programs. From 1996 to 2005, he served in multiple roles of increasing responsibility at Ardea Biosciences, first as vice-president, Clinical Affairs, then as president and chief operating officer, and finally as CEO. From 1987 to 1996, Dr. Fuchs held various positions at Genentech where, among other responsibilities, he led the clinical program that resulted in the approval of Pulmozyme. Dr. Fuchs was also responsible for the Phase 3 development program that led to the approval of Herceptin to treat metastatic breast cancer. Dr. Fuchs received an M.D. degree from George Washington University and a B.A. in biochemical sciences from Harvard University.

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March 2012 Laboratory Focus www.bioscienceworld.ca

PhARMA noTes

Paladin Labs Inc. (Montreal, QC) and Somaxon Pharmaceuticals, Inc. (San Diego, CA) announce that Paladin has filed a New Drug Submission (NDS) that has been accepted for review

by Health Canada for Silenor® (doxepin) for the treatment and symptomatic relief of insomnia.

If approved, Silenor® could be the first and only prescription product approved for the treatment of insomnia in Canada that is not a controlled substance.

Paladin received rights to commercialize Silenor® in Canada, South America and Africa from Somaxon in June 2011. Under the collaboration agreements, there is no payment due to Somaxon from Paladin as a result of the NDS filing. Once Silenor® is commercialized in the licensed territories, Somaxon will be eligible to receive sales-based milestone payments of up to US$128.5 million as well as a tiered double-digit percentage of net sales.

Oncolytics Biotech Inc. (Calgary, AB) has entered into an agreement whereby the NCIC Clinical Trials Group (CTG) at

Queen’s University, will sponsor and conduct a randomized Phase 2 study of REOLYSIN® in patients with recurrent or metastatic castration resistant prostate cancer.

The study will be an open-label, randomized, non-blinded, Phase 2 clinical study of REOLYSIN given in combination with docetaxel versus docetaxel alone. Approximately 40 response evaluable patients will be enrolled in each arm.

Aeterna Zentaris Inc. (Quebec, QC) has entered into a collaboration agreement with Ventana Medical Systems, Inc., a member of the Roche Group, to develop a companion diagnostic for the immunohistochemical determination of luteinizing hormone-releasing hormone (LHRH) receptor expression, for the company’s doxorubicin LHRH targeted conjugate compound, AEZS-108. In humans, LHRH receptors are expressed in a significant proportion of endometrial, ovarian, breast, bladder, prostate and pancreatic tumors.

AEZS-108 specifically targets LHRH receptors and therefore, could prove to be more efficient in treating patients with these types

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of LHRH-receptor positive cancers.

Phase 2 trials with AEZS-108 for LHRH-receptor positive advanced endometrial and ovarian cancer have recently been successfully completed.

DiagnoCure, Inc. (Québec, QC), announces that the US Food and Drug Administration (FDA) has approved Gen-Probe’s (San Diego, CA) PROGENSA® PCA3 (Prostate Cancer Antigen 3) assay, the first molecular test to help determine the need for repeat prostate biopsies in men who have had a previous negative biopsy. The PROGENSA PCA3 assay is indicated for use in conjunction with other patient information to aid in the decision for repeat biopsy in men 50 years of age or older who have had one or more previous negative prostate biopsies and for whom a repeat biopsy would be recommended by a urologist based on the current standard of care, before consideration of PROGENSA PCA3 assay results. A negative PROGENSA PCA3 assay result is associated with a decreased likelihood of a positive biopsy. A prostate biopsy is required to diagnose cancer. FDA approval of the PROGENSA PCA3 assay was based on a clinical study that began in August 2009 and concluded in May 2010. The study enrolled 495 eligible men at 14 clinical sites. Gen-Probe submitted a Premarket Approval Application (PMA) to the FDA in August 2010.

Sirona Biochem Corp. (Vancouver, BC) has completed a pivotal proof of concept study of its biological inducer for recombinant protein manufacturing. In the study, Sirona Biochem’s inducer produced more protein compared to a leading commercially available inducer at the same concentration. In addition, Sirona Biochem’s compound induced synthesis of a soluble recombinant protein in Escherichia coli for up to 24 hours. Inducers are carbohydrates which trigger recombinant protein production. The quality of the inducer is key to the production process and can affect the quality and yield of the protein.

Current inducers, because they are carbohydrates, are metabolically unstable, and require special handling conditions Tekmira Pharmaceuticals Corporation (Burnaby, BC) announces commencement of patient enrollment in its Phase 1 clinical

2/16/2012 10:43:23 AM

trial for TKM-Ebola. The Phase 1 TKM-Ebola clinical trial is a placebo-controlled, single-blind, single-ascending dose study with additional multiple-ascending dose cohorts in healthy human volunteers. The objective of the Phase 1 trial is to assess the safety and tolerability of TKM-Ebola and evaluate the pharmacokinetics and systemic exposure following both a single-ascending dose (SAD) and multiple-ascending doses (MAD) of TKM-Ebola. A maximum of 56 healthy adult subjects will participate in this study, in two stages. In stage one, the SAD phase will have up to six cohorts with four subjects (three receiving TKM-Ebola and one receiving placebo) in each cohort. In stage two, the MAD portion of the study will have up to three cohorts with four subjects per cohort (three receiving TKM-Ebola and one receiving placebo) in each cohort. TKMEbola will be developed under specific FDA regulatory guidelines (called the “Animal Rule”), which are designed to advance therapeutics that cannot meet the requirements for traditional approval because human efficacy studies are not feasible.

Immunovaccine Inc. (Halifax, NS) has entered into a research collaboration to advance the development of next generation biodefense vaccines. The vaccine candidates will be evaluated as part of a U.S. National Institutes of Health (NIH) funded study, starting in the first quarter of 2012.

The study combines Immunovaccine’s DepoVax™ adjuvanting technology platform with four biodefense vaccine candidates, developed in collaboration with a partner. Results from initial studies warranted further development of the vaccine candidates.

The candidates will be tested in a non-human primate challenge model by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID). The study will evaluate the potential for the candidates to protect against anthrax and multi-filoviruses (e.g., Marburg). These bioterrorism agents are classified as Category A by the U.S. Centers for Disease Control and Prevention. Category A agents have the greatest potential for adverse public health impact with mass casualties because they are easily transmittable and have high fatality rates.

www.bioscienceworld.ca

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Laboratory Focus March 2012

Feature

B y Epp e n d o r f A G

Reducing the risk of repetitive strain injury (RSI) caused by manual pipetting

What is RSI? Repetitive strain injury is a potentially serious form of strain in small muscle groups, caused by carrying out a highly repetitive task for extended periods without a break. Symptoms usually emerge gradually over several months or even years; in serious cases RSI may cause long-term injury to nerves, muscles, tendons or joints.

Because of the repetitive nature of manual liquid handling and its everyday use in biomedical laboratories, pipetting is considered a potential cause of RSI, with associated pain in the finger, thumb, forearm, elbow, shoulder, neck or lower back.

Factors affecting the development of RSI include the weight of the pipette, the effort required for operation, and the user’s posture, technique and work environment.

Pipette buying guide The ergonomics of pipette design has become an important factor in user acceptance and buying decisions, now that accuracy has been optimized and users are more aware of the potential risks of RSI associated with manual pipetting.

According to the UK Institute of Ergonomics & Human Factors, ‘Ergo-

nomics is the application of scientific information concerning humans to the design of objects, systems and environment for human use.’ Utilizing knowledge of anatomy, physiology and psychology, ergonomists aim to analyze tasks and understand users, so that the design of technological equipment and systems is focused on human needs and capabilities. This human-centered design approach enables more productive working and protects health and wellbeing.

Professor Ralph Bruder, Director of the Institute of Ergonomics at Darmstadt University of Technology, has worked with Eppendorf for over 20 years, providing advice on the design of new pipette prototypes at every stage of development and evaluating the ergonomic quality of finished products.

According to Professor Bruder, in

order to ensure that the risks of RSI are minimized, there are a number of important questions to consider when buying a pipette: • What will be the pattern of use: occasionally/for brief periods or frequently/for prolonged periods?

Heavy use means increased risk; therefore it is important to find a pipette which is right for the user and the task.

• For what applications will the pipette be used? For example, what volumes will you be working with?

• Does it fit comfortably in your hand? Consider the pipette diameter, the shape of any finger rest and whether or not it feels heavy.

• Check the position of the controls: e.g. do they require excessive stretching of your thumb which may lead to painful strain damage?

• How high are the forces required to operate all functions, including tip ejection and volume adjustment?

The higher the forces, the greater the risk of strain.

• Think about your work environment: will you be sitting or standing while pipetting? The longer the length of the pipette, the higher you will need to raise your arm when sitting and this could quickly become very tiring.

• Similarly, working in a confined

Figure 1 Starting forces (1000 µL) Ending forces (1000 µL)

Eppendorf Research plus

Competitor A

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1N

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March 2012 Laboratory Focus www.bioscienceworld.ca

feATuRe figure 2 Eppendorf Research plus

<= 10 µL 10–100 µL 100–1000 µL

Competitor A

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50 g

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a suitable alternative activity using different muscle groups may take the place of a break. Similarly, alternating hands, switching between sitting and standing, and regular stretching exercises may be beneficial.

Good posture is significant in preventing RSI, whether sitting or standing to pipette. Any non-neutral positions, such as rounded shoulders, a pronounced bend in the wrist, a twisted forearm, or high lifting of the arm will exacerbate strain when pipetting.

Keep your arms close to your sides, with wrists straight, and avoid resting your elbows on hard bench surfaces.

Hold the pipette with a loose, relaxed grip, not tightly, and use minimum force to apply tips. Selecting the tips recommended by the pipette manufacturer will ensure best fit with the least force; poorly fitting tips will require greater force or repeated ‘rocking’ movements.

space such as a biosafety cabinet and loading vertical gels can be problematic if they require nonneutral alignment of the shoulder, wrist and fingers.

• Single or multichannel? Consider a multichannel pipette when working with multiwell plates; less repetition means less risk of strain.

• Manual or electronic? Electronic pipettes tend to be a little heavier than manual models but they require less effort to operate. There will be some form of control interface; look for one which is self-explanatory and as intuitive as possible, so that you can work efficiently and minimize errors.

How can pipette design mitigate the risks of RSI? The Institute for Ergonomics and Design Research at the University of Duisberg-Essen has carried out numerous studies on the ergonomics of pipetting. By attaching sensors to various muscles in the arms and hands of test subjects, detailed measurements of the muscular energy requirement for standardized pipetting tasks can be compared.

Standardized questionnaires are used to assess users’ views on the pipette weight, the grip design, and the mechanisms for tip attachment/ ejection and dispensing. High ratings for thumb strain are associated with use of pipettes with high dispensing forces, while heavier pipettes prompt high subjective ratings for forearm strain.

Incorporating ergonomic principles into pipette design can help prevent RSI. For example, even a small decrease in weight reduces significantly the strain in muscles needed to hold a pipette, particularly when working for longer periods of time.

The risk of RSI is further reduced by minimizing the operating forces needed for fitting the tip, aspiration

and dispensing of liquids, blow-out and tip-ejection.

The shape and positioning of control elements is also crucial to reducing strain and ensuring intuitive usage and smooth workflow. Optimizing form and function for easy operation, even for complex pipetting tasks, ensures comfortable handling, while low maintenance, color coding for instant recognition, and an easy pipette-tip matching system all contribute to ease of use.

Pipetting technique In addition to choosing an ergonomically designed pipette and matching the pipette to the task and the user’s hand size, it is also very important to use pipettes in accordance with good practice with regard to factors such as rest breaks, posture and technique.

Manual pipetting tasks should be carried out with regular breaks: for example, a three-minute break after 15 minutes’ work, or breaks of longer than 15 minutes during work periods in excess of 30 minutes. A change to

The working environment Various factors in the working environment affect the risk of developing RSI so it makes sense to review the ergonomics of the whole work space.

For example, the height and layout of the workstation, as well as the height and adjustability of the chair and footrest, will be important in promoting good posture.

Placing the tip rack or other frequently used items too far away is a common cause of awkward reaching, which can be harmful over a prolonged period.

Reducing noise from laboratory equipment, maintaining a comfortable ambient temperature, and providing a well-lit workstation all decrease stress in the workplace, and at the same time decrease the risk of developing RSI.

Eppendorf pipettes Eppendorf responded to the need to protect users’ occupational health by creating manual dispensing systems which are perfectly balanced, require minimal user exertion and of-

fer intuitive operation. These include the Eppendorf Reference, Research plus, Xplorer and Multipette ranges of manual and electronic dispensers.

Eppendorf has developed models weighing up to 30 per cent less than comparable pipettes from other manufacturers. For example, the latest Research plus pipette incorporates an ultra-light PerfectPiston system made of Fortron, an advanced organic polymer material. The Eppendorf Research plus and Xplorer pipettes feature a spring-loaded tip cone, designed to achieve optimal tightness with up to 50 per cent less effort than with other brands of pipettes, and the tip ejection forces are similarly low.

Further reading 1. Baker, P and Cooper, C. 1998.

‘Upper limb disorder due to manual pipetting.’ Occupational Medicine. Vol. 48, pp.133–134.

2. Burt, Cindy. ‘Selection and use of pipettes.’ UCLA Ergonomics, NECE Las Vegas, November 2005.

3. Bruder, Ralph. 2003. ‘Evaluating the ergonomic design of pipettes.’ BioForum Europe. 7/6: 338.

4. Bruder, Ralph. ‘Expertise: Ergonomic quality of Eppendorf piston-stroke pipette Reference® .’ Eppendorf, April 2006.

5. Bruder, Ralph. ‘Expertise: Ergonomic quality of Multipette® stream and Multipette® Xstream US: Repeater® stream/Xstream.’

Eppendorf, April 2006.

6. David, G. and Buckle, P. 1997.

‘A questionnaire survey of the ergonomics problems associated with pipettes and their usage with specific reference to workrelated upper limb disorders.’

Applied Ergonomics, Vol. 28, No. 4, pp.257–262.

7. Ewald, Kornelia. 2005. Liquid Handling: Laboratory Practice.

Verlag Moderne Industrie.

8. Hoskins, Donna B, and Erickson, Joan. ‘Laboratory Ergonomics, the wake-up call: How one company relieved stress and strain on its employees.’

9. Chemical Health and Safety, January/February 1998.

10. OHSAH, Vancouver, BC. 2003.

‘Reducing the risk of musculoskeletal injury in healthcare laboratory technologists performing pipetting tasks.’ www.ergonomics.org.uk

Learn more about Advances in Liquid handling on our Lab News Web Portal at www.bioscienceworld.ca

www.bioscienceworld.ca Laboratory Focus

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March 2012

feATuRe

In vivo small animal

B y : Guo B I n M A

OPTICAL IMAGING

figure 1. schematic of photon propagation related to fluorescence process in tissue.

Introduction The ultimate goal of in vivo small animal molecular imaging is to provide a tool for researchers to intactly probe the inside of a small animal in order to obtain pathological information, monitor neurological activities, examine disease progression or regression, track drug distribution, and evaluate drug efficacy in cellular or molecular level.

To reach the goal, a bio-

marker or reporter is usually required. It can be either administrated to an animal or born with the animal through gene modification. Also, a device is required to ‘see’ the reporter. In optical imaging, the device is usually a photon detector that records the photons emitted from the reporter. Very often, the reporter needs to be activated by an external light source to emit photons. This is fluorescence imaging. In other cases, the reporter can be activated by a chemical reaction. That is bioluminescence imaging.

Technology There are a few approaches for in vivo small animal optical imaging. In terms of photon detector used, it can be either charge-coupled-device (CCD) or photomultiplier tube (PMT). CCD usually has

a large field view. PMT is usually more sensitive than CCD. A system equipped with PMT can have a variable field view by raster scanning the imaging subject. The other important feature of a detector is its ability to record the temporal information of photons emitted from reporters, i.e. to acquire time resolved data. This is crucial to properly interpret the imaging results.

In terms of the excitation light source used in imaging systems, it can be a broadband lamp or a laser. The laser itself can be continues wave (CW) or pulsed. A broadband lamp usually covers a wide spectral range, suitable for many fluorescent reporters. Bandpass filter is required for lamp to select a desired spectral band to excite a fluorescent reporter of interest. In practice, due to imperfectness of bandpass filter, leakage of excitation light to fluorescent channel is not avoidable. This will contaminate the measured fluorescent signal and limit the specificity and the sensitiv-

ity of an imaging system. A laser is usually brighter than a lamp and has narrow spectral band. Specific laser can be chosen to excite certain reporters. The narrow band of laser spectrum avoids the excitation light leakage to the fluorescent channel. Recently, wavelength tunable laser is used as the excitation light source in some commercial systems. In these systems, the laser wavelength can be tuned to match the excitation spectral band of fluorescent reporters to optimize the excitation. Wavelength tunable laser combines the advantages of broadband lamp and single wavelength laser.

Fluorescence is a transient phenomenon. If pulsed excitation laser and time resolved detector are used, the temporal information of fluorescent photons can be recorded that allows one to compute the fluorescent lifetime of reporters. As will see later, there are a few advantages of using fluorescent lifetime in small animal optical imaging. The other benefit of time resolved

measurement is to precisely determine the origins of fluorescent photons, i.e. location of the fluorescent reporters.

In terms of imaging configuration, depending on the placement of excitation light source and photon detector, an imaging system can be either trans-illumination (source/detector in the opposite side of a sample) or epiillumination (source/detector in the same side of a sample). The two configurations are also known as transmission or reflection modes. Optical signal in reflection mode is always less attenuated for fluorescent sources located in the first half of a sample due to overall shorter photon path length. Transmission mode has advantage if fluorescent sources locate in the second half of a sample. However, if the sample is flipped over, reflection is superior to transmission mode again.

Challenges In fluorescent microscopy, excitation photons directly illuminate a sample, and fluo-

10

March 2012 Laboratory Focus www.bioscienceworld.ca

Feature

rescent photons directly reach the detector through fluorescent filter.

For in vivo small animal fluorescent imaging, the scenario is more complicate. Figure 1 is a schematic illustrating the scenario. The excitation photons illuminate the skin of a small animal. Some of the photons will be reflected or scattered away, and some of the photons will go through the skin and propagate inside the animal tissue. The propagation of photon inside living tissue is completely different from the photon propagation in air. First, a big part of the photons will be absorbed by tissue.

Some chromophores in tissue will emit fluorescent photons after they absorbed excitation photons. This is the so-called tissue autofluorescence (not shown in Figure 1). Second, the remaining photons will be scattered.

The average free path length of near infrared (NIR) photons in tissue is about 1 mm. In other words, there will be almost no photon propagating in a straight line longer than 1 mm before being scattered. After scattering, the propagation direction of a photon is random. The scattered photons have a new chance to be either absorbed or scattered (together also known as diffused). This process is recursively repeated. Only a small portion of photons will reach the fluorescent reporter deep inside the animal. The reporter absorbs these excitation photons and emits fluorescent photons at longer wavelength. The fluorescent photons will propagate inside tissue in a similar manner as the excitation photons. A small portion of these photons will reach the skin of the animal. Part of them will escape from the skin and some of them will reach the detector through fluorescence filter.

Figure 3

The above scenario can help us identify the challenges of in vivo optical fluorescence imaging. First, light attenuation is severe due to photon scattering and absorption (or diffusion). In the NIR spectral range, for every 2 mm photons traveling, the attenuation is about 1 order of magnitude. In visible spectral range, the attenuation is even more severe. This implies that the detector used in the imaging systems must be very sensitive in order to detect enough number of photons coming from fluorescent reporters deep inside tissue.

Second, the requirement of fluorescent filter is higher. In fluorescent microscopy, fluorescent signal is about one or two orders of magnitude smaller than the excitation light. For in vivo fluorescence imaging, the fluorescent signal in front of the detector is much smaller than the excitation light, depending on the location of a reporter.

Third, if the fluorescent emission band of the reporter overlaps with tissue autofluorescence, the signal detected will be contaminated. There is a wide variety of molecules present in living tissue that can act as biochemical sources of autofluorescence. Examples including tryptophan, NADH, pyridoxine, collagen, elastin, flavins, porphyrins as well as chlorophyll present in animal food.

Most of them can be found in animal skin. As a result, tissue autofluorescence is often stronger than the fluorescent signal from reporter deep inside tissue.

In addition, due to the intrinsic diffusion feature of photon propagation in tissue, there is no straight link between a location on animal skin where a fluorescent photon is detected and the origin of the photon,

Fluorescence intensity and lifetime images acquired using an Optix imaging system for mice injected with AOI987. Refer to text for details.

Figure 2

Reconstructed 3D Cy5.5 distribution in a mouse.

i.e. the reporter location. Model correction must be applied to the measured photons in order to recover the reporter location. From this point of view, no matter how high spatial resolution a detector (e.g. high resolution CCD) is used in an in vivo imaging system, the spatial resolution of mapping the result image to the location of a reporter of interest is mainly determined by the correction model employed.

Solutions By addressing all the challenges of in vivo optical small animal imaging, the new Optix® system1 (MX3) by ART is designed to visualize, characterize and quantify cellular and molecular events in living animals using fluorescent reporters. Based on time domain approach, the Optix MX3 system is configured in reflection configuration with pulsed laser(s) as excitation light source(s), and PMT coupled with time correlated single photon counting (TCSPC) board as detection module. The system is fully automated and computer controlled with a lot of smart features. A special software package, OptiView, is dedicated to data analysis with many powerful and convenient features.

Spectral coverage and system sensitivity Up to 10 fluorescent filters are available in Optix MX3 to meet all spectral requirements of any fluorescent emission in the Vis-NIR spectral range (480 nm to 900 nm). Optix MX3 equipped with tunable pulsed laser has the capability to excite any fluorescent reporters in the whole Vis-NIR spectral range.

The sensitivity of an imaging system refers to its ability to detect signal from a very low amount of fluorescent reporter of interest. Given the

challenges of in vivo optical imaging, sensitivity contains two folds of meaning: First, the system must be able to detect very small numbers of fluorescent photons from a reporter deep inside an animal. PMT coupled with TCSPS module used in Optix enables it to count every single photon.

Second, the system must be able to separate the photons of interest from those unwanted noise photons. The Optix MX3 system is equipped with high quality filters. On top of this, the point-illumination and point detection design provide an additional increase of the filter rejection power by more than two orders of magnitude.

This feature makes Optix the most sensitive in vivo fluorescence imaging system. An independent study done by Dr. Keren et al. showed that the sensitivity of Optix is doubled compared to other imaging systems2.

Decouple fluorophore location/ concentration and 3D tomography The fluorescence signal measured in vivo experiences light attenuation due to photon scattering and absorption by tissue. Without adequate correction of diffusion effect, the conclusion drawn from intensity image alone may mislead user. Using the time-of-flight information carried by time domain measurement, Optix is able to reconstruct the 3D concentration distribution of fluorescent reporter inside a mouse in a quantified way3. The example shown in Figure 2 is the imaging result of a mouse 15 minutes after tail vein injection of Cy5.5. By 3D volume reconstruction, we are able to quantify that the relative Cy5.5 distribution in the mouse brain, neck, left and right kidney, and the bladder regions are respectively 84, 192, 396, 451, and 178.

Continued on page 15

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Feature

AutoGenomics

Revolutionizing Molecular Testing Genomics research is creating innovative, groundbreaking discoveries that are changing the way diseases are diagnosed, monitored, and managed. As a result, physicians must have the ability to closely monitor the progression of disease with a unique signature of genomic markers. This will enable them to make an informed decision on diagnosis and therapy. Targeted therapeutics are being developed to address specific protein products of these genes, most significantly in the field of oncology.

One such example is trastuzumab (Herceptin®; Genentech, Inc.), which is a drug used to treat breast cancer and targets the protein product of the HER2 gene. The efficacy of the drug in treating patients with metastatic breast carcinoma is predicted by the overexpression of HER2/neu protein, thus making it a valuable test in the management of breast cancer. Another phenomenon that influences efficacy of cancer treatment via chemotherapy is multi-drug resistance (MDR). MDR generally occurs when the cancer cells transport certain chemotherapeutic drugs from inside their cell to the outside. Such resistance can occur, for example, if there is an over-expression of the trans-membrane permeable glycoprotein, which appears to act as a drug efflux pump, inhibiting the rise in the intracellular concentration of anticancer drugs. The diagnosis of potential drug resistance (whether single or multiple) is, therefore, also another critical step in determining which form of chemotherapy is likely to be most effective. Administering an ineffective drug can cause chemotoxicity in the patient, which leads to adverse side effects and impedes timely treatment.

B y : Da n n i s Fa f ar d

www.bioscienceworld.ca

With these advances in understanding disease and treatment relationships at the molecular level, the increasing importance of pharmacogenomics is now being recognized by the drug industry in many applications even stemming beyond oncology. It is at last understood that individuals should be treated based on their genetic make-up rather than just symptoms alone. As an example, the cytochrome P450 2D6 (CYP2D6) enzyme is involved in the metabolism of tricyclic antidepressants, antipsychotics, β-adrenergic blockers, and antiarrhythmics, and it is believed to be responsible for greater than 70 different drug oxidations.

The deficiency of the CYP2D6 enzyme is inherited as an autosomal recessive trait with seven per cent of caucasians classified as poor metabolizers. Since there may be no alternate metabolic pathways to clear these drugs from the system, poor metabolizers may be at severe risk from adverse drug reactions. The need to enhance diagnostic methodologies to allow for the determination of a patient’s metabolic character will be crucial to the timely treatment of even the most mundane of patient ailments.

The culmination of this cutting edge research is now leading to the development of new diagnostic tests. Genetic mutations of diseases, such as cystic fibrosis and Tay-Sachs, can now be positively identified at birth. To facilitate early treatment, better management and reduce healthcare costs, many regions have begun the mandatory screening of a number of inherited genetic disorders, including cystic fibrosis. Although newborn screening and genetically inherited disease detection are the current focus of research, disease management is becoming the key driver for future growth. Recent advances in genomic research have uncovered numerous gene targets that are leading indicators of major diseases, including cancer, cardiovascular and psychiatric disorders.

These complex disease states have multiple genetic markers that offer information on the presence and progression of a particular disease. Molecular diagnostics has a number of applications for disease management, including: • Early diagnosis: early iden-

13

Laboratory Focus March 2012

tification of genetic mutations will enable early diagnosis and risk stratification of specific disease states, leading to administration of proactive treatment protocols.

• Pharmacogenomics: characterization of the body’s in-

teraction with pharmaceuticals at the molecular level will assist in the choice of treatment options, increase the awareness of interactions among multiple drugs, and allow physicians to prescribe more customized dosages for each patient.

feature • Theranostics (therapy and diagnostics): creation of tests that can identify which patients are most suited to a particular therapy and providing feedback on how well a drug is working in order to optimize treatment

regimens.

With these goals in mind, AutoGenomics has created an automated multiplexing microarray platform to make genomic analysis routine and efficient for clinical and research laboratories. While the emergence

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March 2012 Laboratory Focus www.bioscienceworld.ca

feATuRe the BioFilmChip® microarray is based on a polyester film coated with proprietary multilayered matrices. it minimizes background fluorescence and provides significant performance and cost advantages over traditional microarrays.

of microarrays has advanced genomic analyses, a number of underlying issues, such as cross-hybridization, poor spot morphology and intrinsic fluorescence of the solid substrate, have yet to be fully resolved. Current methods use discrete instrumentation, are manual and require highly skilled labor, which leads to inconsistent results. AutoGenomics’ automated platform uses a three-dimensional BioFilmChip® microarray to circumvent these issues, providing optimal spot morphology and utilizing solution-based hybridization with allele-specific primer extension to improve single-base discrimination. AutoGenomics is developing applications for the early detection and management of complex disease states in oncology, cardiology, and mental disorders.

AutoGenomics’ multiplexing microrarray platform, the INFINITI® System, seamlessly brings genomic samples into the realm of automated molecular testing; thus, this platform enhances lab work flows by delivering sample to result without manual intervention. The INFINITI® System, therefore, offers the following distinct benefits to the user: • Multiplexing capabilities: given that most diseases are caused by multiple genetic mutations, the ability to multiplex multiple markers on the same microarray enhances productivity and workflow.

• Fully integrated platform: integration all of the discrete processes in genetic analyses such as fluidics, hybridization, stringency, optical detection and result analysis into a self-contained platform.

• Lower requirement for skilled labor: the ‘load and go’ design allows the system to be operated by less skilled laboratory technicians in contrast to the highly skilled individuals needed to perform manual genetic tests.

• Compelling economics: enhanced productivity and work flow provides a cost-efficient solution.

The key components of the system include the BioFilmChip® microarray,

the Intellipac® reagent management module, the INFINITI® Analyzer and Qmatic® Operating Software.

The BioFilmChip® microarray is based on a polyester film coated with proprietary multilayered matrices. It minimizes background fluorescence and provides significant performance and cost advantages over traditional microarrays. The BioFilmChip® microarrays are offered as ready-to-use microarrays, preloaded with immobilized probes for clinical use and are customizable for research, life sciences and clinical trial applications.

The Intellipac® reagent management module is a unique reagent management system that contains all of the necessary reagents to perform a test. The on-board microchip efficiently manages the reagents, electronically records all relevant reagent specific information, such as expiration date, reagent usage and operator usage data, and contains the assay protocol for a specific test.

The INFINITI® Analyzer is a plugand-play platform that integrates all of the discrete processes of sample handling, reagent management, hybridization, detection and result analysis of DNA. The analyzer has been designed to operate on a ‘load-and-go’ concept. In order to run a test, the operator generates a work list, loads the samples, BioFilmChip® microarrays and Intellipac® reagent modules, and then walks away. The tests are processed automatically and read by the builtin confocal microscope. Results are analyzed and presented in a customized graphical format for easy interpretation. The used chips are discarded in the waste drawer for easy disposal. The system can process 24 microarrays simultaneously.

Qmatic® Operating Software is a proprietary software module built into the INFINITI Analyzer that manages multiple processes in genomic analyses. The Qmatic® software’s random access capability allows the INFINITI® Analyzer to simultaneously manage multiple tests with differ-

ent methodologies on a continuous flow basis.

The INFINITI® Analyzer’s ‘open architecture’ design enables adaptation of multiple methodologies, such as hybridization assay, allele-specific primer extension assay to perform single nucleotide polymorphisms (SNPs), short tandem repeats (STRs), microsatellite analysis, and gene expression analysis. With this array of capabilities, AutoGenomics is now developing a wide spectrum of applications in genetic disorders, pharmacogenomics, biomarkers in oncology, infectious diseases, cardiology and mental disorders.

AutoGenomics plans to use its versatile platform as a valuable tool to screen for biomarkers. Biomarkers of disease play an important role in drug discovery and development by providing clues to genetic susceptibility, disease progression and predisposition, as well as offers information on physiologic and metabolic

profiling of diseases. Of note, the ability to multiplex several markers on the same chip has enabled the company to make progress in developing a novel genotyping assay for the accurate determination of high- and low risk human papillomavirus (HPV) types. Ideally, an HPV test should allow for the detection of multiple HPV types, identify individual types, and provide quantitative information about the viral load of each individual type found. The availability of these new-wave markers has played a key role in providing tools for early disease detection, prognosis, and monitoring, in addition to improving the time and cost-efficiency of drug development. AutoGenomics also plans to develop DNA fingerprinting and agricultural applications.

To find out more about the features of the AutoGenomics INFINITI® technology please visit www.autogenomics.com.

Learn more about Molecular Biology Systems on our Whitepapers Web Portal at www.bioscienceworld.ca

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Laboratory Focus March 2012

feATuRe

continued from page 10 Advantages of using fluorescence lifetime There are several advantages of using fluorescence lifetime in optical small animal imaging. First, since lifetime is an intrinsic characteristic of a fluorescent reporter, it adds another parameter to distinguish fluorescent reporters. Lifetime can be used to differentiate fluorescent photons from reporter or tissue autofluorescence. Lifetime can also be used to differentiate reporter from bound or unbound state.

Second, for certain fluorescent reporters, their lifetime is sensitive to micro biological environment, such as pH, pO2, Ca+, etc. In these cases, lifetime can be used to sense the micro environmental condition of neighboring tissues that are important for cancer research. In addition, lifetime is independent of signal amplitude that is a function of many factors such as reporter concentration, light attenuation, excitation laser power, etc. Therefore, lifetime is more reliable and a convenient parameter being used to interpret the experiment results.

Shown in Figure 3 is an example4 of discriminating the bound from unbound state of a reporter by using the lifetime provided by Optix. The images are four different mice, from left to right: Alzheimer disease mouse with AOI987 probe bound to β amyloid plaques; Alzheimer disease mouse without any probe; wild type mouse with the AOI9087 present in the brain unbound; wild type negative control. The intensity images in the top panel show fluorescent signal from all the four mouse brains, while the lifetime images in the bottom panel help us to differentiate these fluorescence signals.

This can potentially be used as a parameter to diagnose Alzheimer disease and monitor its treatment if a therapy drug is administrated.

Summary In vivo small animal optical imaging is a revolutionary technology for biological, medical, and pharmaceutical studies. Time domain approach has numerous advantages in prospective applications. We are looking forward to seeing more exciting results using this powerful tool.

References 1. G. Ma, et al., Appl. Opt. 48, 1650 (2007).

2. S. Keren, et al., IEEE Trans Med Imaging 27, 58 (2008).

3. G. Ma, et al., SPIE Photonics West BIOS 2009 (San Jose, CA).

4. R. Nabuurs, et al., 2010 World Molecular Imaging Congress (Kyoto, Japan).

Learn more about Molecular Biology Systems on our Whitepapers Web Portal at www.bioscienceworld.ca

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New Products Spectrometer The new Eppendorf BioSpectrometer® combines accuracy and sensitivity with outstanding flexibility in a small robust instrument. The BioSpectrometer extends Eppendorf’s current detection product line by offering scanning capabilities allowing routine and complex methods such as measuring cytotoxicity, proteins, fluorescent dyes and more. The BioSpectrometer kinetic model features a temperature-controlled cuvette shaft that requires no additional accessories in order to study enzyme or substrate kinetics. Scanning spectrum as well as individual wavelength measurements can be monitored in the spectral range of 200 nm to 830 nm.

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High Throughput The Möbius for Wyatt Technology Corporation has been developed to automate the measurement of the mobility and the hydrodynamic radius of precious protein samples, increasing throughput without modifying the species. The instrument is designed to facilitate analyses in high-saline conditions, expanding the capability of the laboratory.

While conventional batch-mode zeta potential instrumentation has been incapable of automating macromolecular particle electrophoretic mobility for multiple samples, the Möbius used with an HPLC pump and an auto-sampler, can overcome this challenge. The Möbius offers a unique cell, designed as a closed system, which accepts sample delivery from an autosampler. Once the sample injection sequence is implemented and synchronized with a data acquisition schedule in its Dynamics™ software, automated measurement of multiple samples is enabled. This eliminates the need for manual injection. With the additional possibility of a buffer injection in between samples further enhanced by a wash sequence, cross contamination of cells is minimized, helping to ensure data accuracy.

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March 2012 Laboratory Focus www.bioscienceworld.ca

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Company & Advertiser Index COMPANY

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Website

Aeterna Zentaris Inc........................... 6............................... www.aezsinc.com Air Science USA................................ 16.......................... www.airscience.com Amorfix Life Sciences.......................... 5............................... www.amorfix.com Caledon Laboratory Chemicals.......... 4......................www.caledonlabs.com Canadian Society for....................................................................................

Chemical Technology......................... 6................ www.cheminst.ca/profdev DiagnoCure Inc................................... 6..........................www.diagnocure.com EMD Millipore.............................. 16, 19................www.emdmillipore.com Eppendorf..................................... 16, 20.................... www.eppendorf.com ESBE Scientific/Sanyo...................... 11................................www.esbe.com Immunovaccine Inc.............................. 6............................www.imvaccine.com MethylGene Inc.................................. 5......................... www.methylgene.com Miele Professional...........................3,5............. www.mieleprofessional.ca Oncolytics Biotech Inc......................... 6.................www.oncolyticsbiotech.com Paladin Labs Inc.................................. 6.......................... www.paladinlabs.com Pfizer Canada Inc................................ 5.....................................www.pfizer.ca Sirona Biochem Corp.......................... 6..................... www.sironabiochem.com Tekmira Pharmaceuticals Corp............. 6......................www.tekmirapharm.com Thermo Fisher Scientific................... 2............................. www.fishersci.ca VWR................................................ 13................................. www.vwr.com Wyatt Technology.............................. 16................................ www.wyatt.com

www.bioscienceworld.ca Laboratory Focus

MARCH March 11-16

March 2012

Calendar

Tel: (905) 667-8688 Fax: (905) 528-4968 Email: labcon@csmls.org Web: www.csmls.org

June 17-20

PITTCON Conference & Expo Venue: Orlando, FL June 12-15 Tel: (412) 825-3220 RC_lab_new:Layout 1 1/19/2012 9:27 AM Page 1 Fax: (412) 825-3224 Canadian Society for Pharmaceutical Email: info@pittcon.org Sciences Symposium Web: www.pittcon.org Venue: Toronto, ON Tel: (780) 492-0950 March 19-21 Fax: (780) 492-0951 Email: bberekoff@cspscanada.org Bio-Europe Spring 2012 Web: www.cspscanada.org Venue: Amsterdam, The Netherlands Tel: (760) 930-0500 Email: chundschell@ebdgroup.com Web: www.ebdgroup.com/bes/ index.php

Email: reg2012@bio.org Web: www.convention.bio.org

CSCC Conference Venue: Quebec City, QC Tel: 613-531-8899 Fax: 613-531-0626 Email: office@cscc.ca Web: www.cscc.ca

June 25-27

June 18-21 BIO International Convention Venue: Washington, DC

PrP Canada and Protein Folding Conference Venue; Toronto, ON Tel: 604-222-3600 Fax: 604-222-3606 Email: admin@prionetcanada.ca Web: www.prionetcanada.ca

March 28-30 ACETECH Symposium Venue: Whistler, BC Tel: (604) 683-5852 Fax: (604) 683-3879 Web: www.acetech.org

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April 17-20

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Analytica 2012 Venue: Munich, Germany Tel: 416-237-9939 Fax: 416-237-9920 Email: bmertens@canadaunlimited.com Web: www.analytica.de www. canada-unlimited.com/

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April 29-May 2 World Congress on Industrial Biotechnology and Bioprocessing Venue: Orlando, Fl Email: info@bio.org Web: www.bio.org/worldcongress

MAY May 20-24 ASMS Conference on Mass Spectrometry Venue: Vancouver, BC Tel: (505) 989-4517 Fax: (505) 989-1073 Email: office@asms.org Web: www.asms.org

May 29-30 BioFinance 2012 Venue: Toronto, ON Tel. 1-866-342-4933 Fax: 1-866-342-4934 Email: kvanvogt@biofinance.ca Web: www.biofinance.ca

JUNE June 2-4 Labcon 2012 Venue: Gatineau, QC

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March 2012 Laboratory Focus

Career Spotlight Bio-economy Career Profile

Vancouver hosts world’s largest science-fest For the first time in more than 30 years, the American Association for the Advancement of Science held its annual conference in Canada.

Once annually, AAAS sponsors this four day conference, which includes symposia, lectures, seminars, workshops and poster sessions covering every area of science, technology and education. And while I didn’t have the pleasure of attending, everything I’ve heard and read indicates it was quite the spectacle.

In all, the event drew more than 8,000 researchers, policy makers and science communicators from over 60 countries. With the opportunity to showcase their work to the world, Canadian researchers and scientists turned out in full force, with more than 170 participating as lecturers and speakers.

Among them was Dr. Julio Montaner, director of the B.C. Centre for Excellence in HIV/AIDS whose pioneering work in using highly active antiretroviral drugs (HAART) to treat those with HIV has had stunning results. Dr. Montaner told AAAS delegates that recent studies have shown this approach to be highly effective with the number of new HIV diagnoses per year in B.C. dropping more than 50 per cent since the HAART treatment program began in 1996. He was one of many Canadian scientists that demonstrated how highly regarded Canada is on the international stage of science.

The event had its share of controversy too, as allegations were made during one of the panel sessions of Canadian government censorship of Canadian scientists and rumblings of reporters being denied access to government scientists without the consent of media relations officers.

Most of the disenchantment falls on current media-relations protocol requiring Canadian scientists working with government organizations to refer inquiries first to communications officers.

Whether it was by design or not, groups representing these scientists and science writers sent an open letter to Canadian Prime Minister Stephen Harper calling for more transparent policy to allow scientists to respond in a timely manner to journalist requests. The letter was signed by several groups including the Canadian Science Writers Association, World Federation of Science Journalists, Canadian Journalists for Free Expression and the Professional Institute of the Public Service of Canada.

The group’s hope is that the Canadian government follows the lead set forth by our neighbors to the south, where the Obama Administration has opened up lines of communication between government scientists and media allowing for more transparency with the media and the public.

As demonstrated at this event, our country is highly regarded on the international scientific scene. It’s something we should be proud of, and our scientists should be allowed to speak proudly about it.

Compiled by BioTalent Canada Position: Senior Manager, Clinical Trial Operations Name: Laura Brodowski Company: ASKA Research Salary Range: $50,000 to $70,000 per year

What I do:

I work for ASKA Research in Vancouver as the Senior Manager of Clinical Trial Operations. ASKA Research is a Contract Research Organization (CRO) that provides clinical research outsourcing services to the investigational product development industry, specifically pharmaceutical, medical device and biotechnology companies. We “fill in the gaps” for companies that may be in any number of phases in the development of drugs and devices. ASKA’s specialty is monitoring and managing clinical trials, ensuring the data provided to the client is accurate and complete. ASKA Research also is contracted to provide educational workshops and assist with the development of training manuals, which provide industry-standard training modules. My role as a project manager is predominantly to manage resources. I am the conduit between the company and the Clinical Research Associates (CRAs) in the field who are providing services at the clinical trial sites. I report the project progress and updates to our client, I review CRA monitoring reports, and I assist in the collection and management of regulatory documentation from physicians involved in the clinical trials. A significant part of my job is to manage many moving targets, timelines and priorities without losing sight and perspective of the “big picture.” One particularly “regulatory” aspect of my role is to manage Trial Master Files that are essentially the auditable paper trail and may be examined by Health Canada or the FDA. My other duties include assisting with managing the training requirements for ASKA employees, and sourcing and contracting resources for the company as needed.

What education and skills do candidates need for this position?

At minimum you need a Bachelors of Science. It is not necessarily having a specialty that ASKA Research looks for, but the relevance of completing a degree illustrates skills and abilities such as diligence; organization; focus; and ability to establish priorities and work under, sometimes, extreme pressure. It is recommended that you have project management training or experience. Formal training isn’t necessary, but a comprehensive understanding of the basic processes and communication requirements is essential. You must be forward thinking, able to project or foresee consequences and mitigate them. Having an understanding and skills related to risk management is also important. Soft people skills are key to working in teams; this requires an understanding of the difference between leadership and management, and when each applies. Some of the traits that can assist you in this job include patience, especially since you work with so many diverse personalities. You need to understand your role in managing differences of opinion and perceptions. You also need to have attention to detail, but most importantly…you must be able to work efficiently under pressure and be willing to do what needs to be done regardless of your title and list of accountabilities. This industry is a remarkable example of teamwork and collaboration, and extended family.

What are the best parts of your job?

The most satisfying part of my job is the diversity of each day and project. I am not afraid of change, so I’m in the right environment! Also, I have experienced the result of a successful drug approval; knowing the rigorous effort that everyone made makes me proud to have contributed even a small portion.

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