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Designing Experiments the Automated Way

Designing Experiments the Automated Way Imagine an industry that is highly technology dependent

Thanks to everyone who provided feedback after our previous blog regarding the future location for the LabAutomation conference. Stay tuned - a decision will be coming this summer!

Today we're discussing Design of Experiments, or DOE, and the combination of that technique with laboratory automation. The LabMan reached out to a long-time expert in the field, Paul Taylor, Principal Scientist at Boehringer Ingleheim, to discuss the topic. Paul indicates that DOE as an experimental approach was developed by Sir Ronald Fisher beginning in 1919 during his work at the Rothamsted Experimental Station located at Harpenden, Hertfordshire, England. In his role there as a statistician he developed the concept of ANOVA, or Analysis of Variants, which is still used today to determine which factors in an experiment produce significant effects and whether the response is linear or non-linear. In 1925 he published Statistical Methods for Research Workers, followed in 1935 by The Design of Experiments.

DOE is an approach to optimizing a given experimental operation in an iterative, efficient and statistically-driven way, by systematically evaluating the impact of individual experimental variables on the final, measured outcome of the experiment. The approach can be relatively simple for experiments involving just a few variables, or quite complex for multi-variant experiments. In all cases, the idea is to rigorously explore the impact of variables in a well-organized, highly systematic way that minimizes the number of tests to be run and maximizes the statistical relevance of the results.

The rub has always been that it can be a lot of work to do DOE on even a moderately complex problem. It can take significant time to design the array, or table of experiments to sufficiently evaluate all the variables inherent to the problem. This requires knowledge of both the science involved and experimental statistics - usually not resident in the same person. It can then be very tedious and time consuming to run all these experiments. In some cases, there may not be enough supply of experimental components (such as reagents) to run all the desired experiments. In other cases, experimental components may not be sufficiently stable across the span of time necessary for a human to complete the entire planned table of experiments. Many, even most scientists will take intuitive shortcuts rather than go through the DOE tedium. Sometimes this works and other times experimental blind alleys end up taking as much or more time than a carefully planned DOE approach would have.

So, we have a powerful experimental approach that has the disadvantage of being tedious, computationally intensive, involving laborious setup, and consuming both time and supplies. It sounds like the ideal situation for the application of computerized design with automated execution! Specifically, for chemical/biochemical experiments, there are now many choices of automated liquid handling systems that can assume the tedium and complexity of executing a DOE array of experiments, and can do so in a fast and miniaturized way. Computerized power for designing a DOE array of experiments and analyzing the results certainly exists. As Paul points out, the key is then in linking the two into a package that intuitively appeals to the scientist.

Several technology providers have taken a stab at this. Paul has spent a good deal of time working with and helping to develop the Automated Assay Optimization (AAO) package sold by Beckman Coulter for their Biomek FX. Symyx has developed Lab Execution software for chemical process optimization using their Benchtop System. Others have developed "home-grown" versions of similar approaches. Paul feels that for such systems to be successful, they must be capable of translating experimental inquiry in the way a scientist would think to the physical and practical reality of automated system execution. This would basically involve an automated system capable of reading a scientist-generated table of experimental parameters together with a range for each parameter, and translating that into a series of automated methods for exploring the response range for each parameter.

If you want a deeper introduction to DOE, sign up for the ALA short course on the topic at the next LabAutomation conference!

Until next time,

Domo Arigato, Mr. Roboto

New location for LabAutomation?

New location for LabAutomation? Imagine an industry that is highly technology dependent

Let me begin this blog by saying that we want your feedback! You may not know it, but you can post comments to this or any LabMan blog by clicking on "add comment" at the bottom of each post. In this case, we're discussing future locations for the LabAutomation conference, so if you have an opinion, please post a comment! Don't wait and grouse when the conference ends up in a place you don't like!

For those not involved with conference planning, it may be surprising to learn that conference venues are planned 3 to 5 years out. To get a specific place at a specific time of year, you have to get into the que early. So, the ALA is now going through that planning process for the LabAutomation 2011 and beyond dates. To demystify this process, The Lab Man talked to Brenda Dreier, the ALA Director of Event Management and to Dr. Jim Sterling, the current ALA president. Brenda related the history of LabAutomation venues. The conference began in 1998 in San Diego, at the Sheraton Harbor Island Hotel. By 2000 the conference had outgrown that facility, and moved to the Palm Springs Convention Center. Growth and pending construction caused the conference to move to the San Jose Convention Center in 2004 and 2005, and then back to Palm Springs in the years since. The conference continues to grow, so what venue will be appropriate by 2011?

Jim pointed out several factors in the pending choice. The end of January time slot is both traditional and beneficial. It's the beginning of the budget year for many attendees, so travel funds may be more available. It's also the beginning of the fiscal year for many of the conference exhibitors, so they are eager to get the year started with a bang, including new product announcements. The ALA has always had a tradition of inviting attendees to take a break from the winter, come to a warm, inviting climate and experience an excellent conference along with mingling with colleagues while enjoying some good food and beverage. All of these factors have helped the conference achieve the current level of success, and it's not wise to mess with winning formulas. That means choosing among cities with warm climates and available facilities in January. Brenda indicates those cities under consideration include Palm Springs, San Diego, Anaheim, Long Beach, Phoenix and Los Angeles.

Unlike some conferences, the ALA tends to stay in a location for multiple years. Multi-year agreements lower the cost and those savings that can be passed on to attendees and exhibitors. The ALA has been able to keep room cost below $200/night during peak demand time in Palm Springs. This practice also lets attendees become familiar with both the convention center and the surrounding locale, so time can be spent more productively. Keeping with this practice, the venue chosen for 2011 will also be the conference site for 2012 and 2013.

What specific factors influence the choice? Obviously, your feedback counts (hint!). From a physical standpoint, the conference requires a convention center large enough to accommodate anticipated growth, but also not so large as to dwarf the event. Attendees like to shuttle back and forth between talks and the exhibit floor, so that needs to be a convenient walk. Exhibitors need sufficient space and pre-conference time for setup. There must be adequate numbers of right-sized rooms for both podium sessions and the extensive short course program. Enough hotel rooms should be available within reasonable walking or shuttle distance. The city itself must be easily accessible by air, given that conference attendees come from all around the country and world. Ideally, there would be a local scientific presence to encourage walk-in attendance. And, naturally, the finances have to be right.

The timeframe for this decision is June of this year. So, if you have an opinion, please post a comment!

Until next time,

Domo Arigato, Mr. Roboto

Innovation and Change at LabAutomation2008

Innovation and Change at LabAutomation2008 Imagine an industry that is highly technology dependent

Once again the LabAutomation conference has provided many of us with a welcome respite from winter and a chance to feel young again amidst the populace of Palm Springs! Our technical field and the conference continue to grow and thrive! This year saw a record attendance of 4670 from some 40 countries. The event continued the tradition of presenting the top 100 podium presentations on laboratory automation, as well as 189 posters, 18 short courses and 21 industry-sponsored workshops. It has truly become an event with more to offer than one can absorb, so a return visit is almost mandatory to stay abreast of new developments.

Speaking of new developments, the acquisition of Velocity 11 by Agilent was announced at the opening evening (sponsored by V11). Thus continues the recent trend previously noted by The Lab Man of consolidation among the vendor community. The Agilent spokesman indicated that his company was very glad to be entering the laboratory automation market and I'm sure that feeling is shared among the user community. Those who have been around as long as The Lab Man will remember, however, that Agilent in its former incarnation as Hewlett Packard was for a while a laboratory automation player with its Automated Chemical Systems line of products, including the ORCA robot. What comes around goes around! Change is often circular.

Even though the prevailing trend in the vendor community is one of consolidation, there are still many new providers entering the market. The ALA continued its program to support and highlight new companies via Innovation AveNEW, which provided booth space to eight startup companies. It should be noted that Velocity 11 got their jumpstart years ago when the conference provided them such a booth, so this program does pay dividends to our community. Innovation is what these young companies are all about, as clearly shown by the fact that two of the three New Product Awards (NPA) went to very young companies. The NPA winners were:

Qiagen, for their QIAsymphony, a highly integrated and user friendly bench top workstation aimed at the DNA and RNA purification and amplification market. The device is highly modular to allow ease of reconfiguration for a broad application range.

Viaflow, for their Vision Pipetting System, a handheld pipette system that finally brings these devices into the wireless and iPod age. It has a very familiar scroll-wheel type control, a full color display for menus and images, and an optional Bluetooth interface for data transfer.

Formulatrix, for The Formulator, a next-generation automated liquid handler using a microfluidic chip to measure and dispense discrete volumes of liquid. The chip has 96 outputs and two metering chambers of 0.2 and 3.0 microliters volume.

The ALA's recognition of innovation is not limited to the exhibit floor. The $10,000 Innovation Award is given each year to the presenter best demonstrating vision, originality, seminal technology, applications and strategies. That award went to James Landers, Ph.D., University of Virginia, for his podium presentation, "A Simplified Microfluidic Device for Ultrafast Genetic Analysis With Sample-In/Answer-Out Capability: Application to T-cell Lymphoma Diagnosis." The ALA offers full travel support awards to students presenting posters and a $1000 award is given to the top student poster. This year the winner was Nicole Tolan, Michigan State University, for her poster titled, "Development of a High-Throughput Microfluidic Array for Detecting Multiple Metabolites From Blood Components to Determine Drug Efficacy and Mechanisms of Action".

Other quick impressions:

The Lab Man found it fascinating to watch the mind of a Nobel Laureate, Dr. K. Barry Sharpless, at work during his plenary address.

Dr. Henry Chesbrough, University of California, Berkley, spoke about changes in the path to innovation and praised the efforts in that regard of Stanford University as the "2nd most prestigious academic institution in California".

Riding a Segway is not only fun, but a real education in how original thinking can lead to devices that are engineered in new and amazingly simple and intuitive ways.

The visiting FIRST students (see previous blog) were an amazingly enthusiastic and bright bunch. We read much about the demise of high-technology education in our country, but you certainly wouldn't know it talking to these kids!

Please check out the podcasts recorded "live" on the exhibit floor at the conference! And PLEASE enter some comments to let The Lab Man know how he's doing!

Until next time,

Domo Arigato, Mr. Roboto

Teaching Microplates New Tricks

Teaching Microplates New Tricks Imagine an industry that is highly technology dependent

The microplate has been around as a 96 well molded tray of "test tubes" since the 1950's, when John Liner at the Linbro Company produced a vacuum formed version. The format concept was originally developed in early 1951 by Dr. G. Takatsky of the N.P.H. in Hungary, where he machined multi-well plates in acrylic for use in Virolgy and Serology testing, which involved multiple serial dilutions. By the early 1960's the NIH was getting heavily involved in Rubella vaccine testing, and an NIH investigator, Dr. John Sever, recognized the microplate concept as a way to mechanize this testing. He and Frank Cooke, of Cooke Engineering, set about to refine the concept, eventually leading to an injection-molded, polystyrene 96-well plate - the style essentially still with us today. Production began in 1965 and Cooke was granted a patent for the microplate and trademark for the name Microtiter by 1968. Shortly thereafter, Dynatech acquired Cooke Labs. Dynatech and Data Packaging Corp. formed a joint venture called CoStar, which was acquired by Corning in 1993. If you'd like to read a detailed history, visit this website assembled by Roy Manns, or read the paper by Tom Astel in JALA Vol 5, Issue 6.

So, other than a bit of nostalgia, what is The Lab Man getting at? Well, the fact that most of the microplates being used today are still made of injected molded polystyrene. Certainly the process is much better controlled and standardized than in 1965. Plates are available in higher density formats, and different colors and opacities. You can even buy very sophisticated plates from Corning with an optical biosensor imbedded in the bottom of each well. But the basic building material is still polypropylene! This is an era of exotic plastics! We build airplanes out of carbon fibers. Nanotubes are all the rage. Surely there are now interesting options available to improve on Cooke's original (and apparently good) choice of polystyrene over 40 years ago? To ask this question, we talked to Lane Niels, a guru and consultant in the field of Assay Biophysics, about new developments in microplate material science.

Lane points out that polystyrene was initially chosen for its clarity, hardness, rigidity and ability to be injected molded. It was also considered to present a largely inert surface, but it was able to be derivatized in a relatively controlled way. While polystyrene still proves to be an excellent material, we now understand a lot more about surfaces and biochemical interactions. No plastic is truly inert in all situations. Conversely, true inertness would be a disadvantage in promoting some biochemical interactions. So we can look at the characteristics of various new plastics and make educated choices.

In Lane's opinion, a material likely to become more popular is Cyclo-Olefin Copolymer (COC). You can read about the plastics technical specifications here. What makes it interesting for microplate use? COC appears to be more inert and is more hydrophobic than polystyrene. Inertness is influenced not only by the chemical structure of the polymer, but also by the process used to initiate the polymerization process. Polystyrene polymerization is activated using strong oxidizing agents, such as stannous ion. Industrial grade oxidizing reagents can often leave behind a minute trace residue of heavy metals, which can affect certain binding assays (i.e. Ca+ binding), especially when working in very low volumes. Lane has reviewed published studies where such binding assays worked fine in typical 96-well volumes, but didn't perform well at lower volumes. The polymerization process for COC is activated thermally, which is much less likely to result in any unwanted chemical residue. COC can be radicalized using gas plasma to facilitate surface derivatization. It has similar rigidity to polystyrene, so COC microplates can be made to be very flat, with very flat well bottoms if desired.

If you want to experiment, ask your local med (not mad) chemist to cook up some COC for you! Or, if you'd rather avoid interacting with synthetic chemists, COC plates are available from various vendors, such as the Beckman Chemlib microplates or those from Aurora Biotechnologies.

Until next time,

Domo Arigato, Mr. Roboto

Microsoft a player in Bioinformatics?

There are always rumors floating around about what next market segment Microsoft will explore

There are always rumors floating around about what next market segment Microsoft will explore.  Will Microsoft take on Google?  Will Microsoft develop an iPhone-like device?  Will Microsoft become a dominant force in bioinformatics?  Wait a minute, bioinformatics?  That’s hardly the same realm as search engines or consumer communications, but it does appear to be a field that Microsoft is interested in.  Take a look at the web site for their Cambridge, U.K. research lab, and you’ll see Computational Biology listed as one of the areas of interest.  A check of their job openings shows that they are hiring people with bioinformatics backgrounds.  So, can we expect someday for a release of “MS Bioinformatics Suite” or have the annoying Clippy animation ask if we need help processing DNA sequence data?  Probably not, but there is no doubt that Microsoft has noticed that life sciences related computation is a growing field and doesn’t want to be left out.  To that end, they were key in forming the BioIT Alliance, a collaborative group consisting of Microsoft and various life science technology providers. 

To learn more about the BioIT alliance, The LabMan spoke to Rudy Potenzone, Industry Technology Strategist for Microsoft.  Rudy indicates that the BioIT alliance was formed in the middle of 2006 to promote a greater level of partnership among providers of bioinformatics tools and to inform them about new technology developments at Microsoft.  Member companies include those focused solely on bioinformatics software as well as laboratory equipment companies whose products include control or data processing software.  The common link is the development of software-containing products aimed at the life sciences market.  Microsoft feels that its core Office products, such as Excel and Word, have long been intertwined with many bioinformatics software applications.  New developments involving and following Vista and Office 2007 will transform those products significantly, so Microsoft felt it was essential to educate bioinformatics providers about their new technology directions. 

There is no cost for a company to become a member of the BioIT Alliance.  The relationship is essentially a co-marketing agreement between a member company and Microsoft.  There are opportunities for members to attend various workshops, seminars and discussion groups focused on the use of various tools or future developments.  Sharing of ideas and applications among members is encouraged.  Rudy says that members often see the use of Microsoft tools in ways they haven’t previous envisioned, such as integrating the Vista workflow foundation with the control of robotic devices.  One recent project with Alliance member Scripps Research Institute involved building a collaborative molecular environment (CME) client-based tool that lets researchers share 3-D information via Microsoft Office SharePoint Server 2007 and Vista.

Rudy expects that soon we’ll begin to see bioinformatics products emerge that take advantage new Microsoft capabilities, and ideally this will provide the structure for many more products to be linked in ways that were not possible or just too difficult in the past.  He mentioned that Thermo-Fisher has recently announced that it has established a working relationship with Microsoft aimed at developing next-generation laboratory knowledge management, based on open guided by NIST and the SAFE consortium for electronic signatures.  The ultimate goal is better information flow among scientists to accelerate the rate of scientific discovery and development.

The LabMan knows from experience that standards and interoperability don’t happen overnight or by chance, but only as the result of a lot of dedicated effort.  The constructive support of an industry heavyweight such as Microsoft may help encourage wider adoption and move efforts ahead faster.  That can’t be a bad thing, if done well. 

Thanks to Velocity 11 for sponsoring this months blog! 

 

Until next time,

Domo Arigato, Mr. Roboto  

Dean Kamen talks about technology education and FIRST

Dean Kamen talks about technology education and FIRST According to a recent note in the EETimes, Americans have been losing interest in EE

According to a recent note in the EETimes, some are theorizing that American students have been losing interest in electrical engineering because the dramatic technological advances in electronics have had the unintended consequence of making electronics less accessible to curious young minds. How many of you became interested in technology via various tinkering opportunities as a youngster. One person who has been actively trying to address this situation is Dean Kamen, the inventor of the Segway Human Transport Device. Dean has established an organization called FIRST (For Inspiration and Recognition of Science and Technology). The mission of FIRST is to inspire young people to be science and technology leaders, by engaging them in exciting mentor-based programs that build science, engineering and technology skills, that inspire innovation, and that foster well-rounded life capabilities including self-confidence, communication and leadership.

Although Kamen may be best known among the general public for his work on the Segway, his background is as an entrepreneur and inventor of numerous biomedical devices, including the first portable insulin pump for diabetics. He holds over 440 U.S. patents and his accomplishments were recognized in 2000 when he was awarded the National Medal of Technology by President Clinton. In 1989 he founded FIRST as a way to get high school age students interested in and excited about science and technology. The approach is to give teams of students the task of creating robotic devices and placing those teams with their creations into competitions that Kamen seeks to make as exciting for the students as a high school football or basketball game. From the first competition involving 28 teams in a New Hampshire high school gym, the program has grown to involve over 100,000 students from all around the world, and will host it's 2008 championship competition in 2008 in the Georgia Dome.

FIRST promotes the ethos of Gracious Professionalism, a way of doing things that encourages high-quality work, emphasizes the value of others, and respects individuals and the community. Gracious professionals learn and compete like crazy, but treat one another with respect and kindness in the process. Key to making this happen is mentoring from volunteers from the field of science and engineering, as well as financial support from industry and technical organizations. To this end, the ALA has agreed to become a financial sponsor of FIRST. To contribute to the mentoring process, the ALA has invited two of the elite FIRST teams of students to attend LabAutomation 2008, where they will display their robotic creations and have the opportunity to mingle with professionals from our field of endeavor.

We come from a profession where "proof is in the data", and there is some real data available to show the impact of FIRST. Recently, Brandeis University's Center for Youth and Communities conducted an independent, retrospective survey of FIRST Robotics Competition participants and compared results to a group of non-FIRST students with similar backgrounds and academic experiences, including math and science. They found among other things, that FIRST students were more than twice as likely to expect to pursue a career in science and technology, and nearly 4 times as likely to expect to pursue a career specifically in engineering.

Paul Gudonis, the president of FIRST will be a closing plenary speaker at LabAutomation 2008, and will talk about the organization and the concept of Gracious Professionalism. The Lab Man will certainly be there to listen with interest, and hopes that many of you will be there as well. Take the opportunity to chat with the high school teams and consider for yourself whether FIRST is something that you and/or your organization should be involved with.

Post a comment and let us know if you're supportive of this ALA initiative!

Until next time,

Domo Arigato, Mr. Roboto

Vision Systems Evaluate Behavior

Vision Systems Evaluate Behavior Imagine an industry that is highly technology dependent

Vision systems have been around a long time in laboratory automation, and before that in industrial automation. The Lab Man remembers in the late 80's watching a video made by Gary Kramer (NIST) where he attached a then-small camera to the bottom of a Zymate robot arm to film the robots-eye view of an automated process. The video nearly induced motion sickness among the audience! The purpose wasn't just fun, but to develop visual error-checking mechanisms in the robot interface to a Hewlett-Packard autosampler. Since then, robot-guiding machine vision has been used in a number of colony-picking robot applications, such as the Genetix QPIX, but has never really become a common component for guiding or checking movements in laboratory robotic systems.

With the growth of PC-based computing power and the decrease in the cost and size of CCD or CMOS imaging devices, image-based detection has become common in High Content Screening and molecular pathology. Some of these applications track visual events over the course of time rather than just one static image, capturing up to 30 images per second, which equates to immense amounts of data. Recently The Lab Man came across an application of vision systems and innovative software that is facilitating a completely new way to log and analyze something that has been of interest for a long time - animal behavior. To learn more, we talked to Dr. Lucas Noldus, founder and CEO of Noldus Information Technology in the Netherlands. They're involved in a number of efforts to analyze animal or human behavior using vision systems and novel software, including the evaluation of human expression and body language, and the analysis of animal gait patterns to identify locomotor defects.

The application that caught the "vision" of The Lab Man was the analysis of mouse or rat behavior as the phenotypic expression of the animals genotype, and subsequently evaluating how that behavior varies as the result of disease, surgical treatment, drug treatment or genetic variation. Dr. Noldus points out that pharmacologists and neuroscientists have a long history of devising mechanisms to stimulate and log mouse behavior, usually based on fixed sensors in a special enclosure designed to evaluate activity or locomotion. This has provided a rather single-dimension insight into very complex behavior and it was often hard to separate behavior as a response to the unique and stressful test surroundings vs. behavior due to drug or disease. Noldus supposed that it would be much better to evaluate changes in animal behavior as they occurred in their regular "home" without the overt intrusion of sensors or devices. Home for a laboratory mouse means their home cage, complete with familiar water, food and bedding.

To accomplish this "low intrusion" behavioral analysis, one must be able to observe and log very subtle changes in animal behavior that may occur in the home cage environment, such as types of body postures, body motions, interactions with other animals and interactions with their environment. Vision systems allow the capture of raw data with enough resolution and detail to observe such subtle behaviors. Noldus has designed home animal cages that unobtrusively incorporate a wide field video camera to capture this data. He and his colleagues then needed to develop software that was capable of isolating and logging subtle behaviors. This required two breakthroughs. In the past, image analysis has required relatively static environments, with stationary test objects and clean, simple, high contrast and reproducible backgrounds to ensure reliable isolation of the test subject image. However, home cage environments present a very dynamic image situation, with bedding, substrate and perhaps food scattered around in ever-changing patterns. The animal itself moves around and may appear differently at various times or angles due to spots or fur texture. So Noldus developed dynamic subtraction algorithms to allow their image analysis software to isolate and monitor the test animals image over long periods of time in the midst of a dynamic environment. Secondly, they developed software tools to track multiple points on the contour of the animal to get a more accurate analysis of various behaviors beyond just simple locomotion and position in space.

This software all runs easily on a typical, high-end PC. In fact, Noldus has designed a high-throughput version where one CPU is used to acquire data from four cage modules. Dozens of these can be networked together to automate an entire animal facility.

For those of you who like to visualize, go to this web page to view some interesting video clips of this technology in action. And be aware, as you sit at your desk doing this, that a vision system may be evaluating your behavior pattern!

Until next time,

Domo Arigato, Mr. Roboto

Is Your Industry Going Hollywood?

Is Your Industry Going Hollywood? Imagine an industry that is highly technology dependent

Imagine an industry that is highly technology dependent. In fact, the creative use of new technology gave birth to this industry and the ongoing evolution of technology continues to have a profound impact. This industry is also totally dependent on a constant stream of creativity, new ideas and intellectual property. As this industry matured, it realized that effective marketing and sales efforts could significantly increase the success of its products. So this industry became dominated by large companies that were vertically integrated all the way from the beginning of the IP creative process through marketing, distribution and final point-of-sales. As these megaliths matured, they needed increasingly larger revenue streams to keep their growth rate high, and so they became more and more dependent on "blockbuster" products and the associated marketing to maintain that growth. The creative process suffered, as only products with perceived "blockbuster" potential got advanced, even though everyone acknowledged that it was very hard to predict what products would be a "blockbuster". So those involved in the creative process grew frustrated, and some left to work for younger, smaller companies that were focused only on the creative process, and which typically contracted with the large, megalithic companies for marketing and sales of their products. Eventually, the large megalithic companies became so ineffective at the creative process that they got out of that business, ceding that portion of the business to the small, creative companies, and focusing on what they were good at - marketing, sales and distribution. And to accompany the many small, IP-creating companies an equal number of small, young technology companies sprung up, for after all, the industry was and is still very technology driven.

Sound a bit like your industry? Well, I'm describing the motion picture industry, but the same scenario at various stages of evolution can be seen across many industries. This was the subject of a recent article by Liam Bernal in The Scientist, entitled "Why Pharma Must go Hollywood". In short, Bernal proposes that the pharma industry is going and must go through this same evolution. It's a fascinating read and in light of that premise, I thought it would be interesting to ponder the evolution of laboratory automation should this scenario come to pass. To assist in this pondering, I enlisted Charles R. Powell, Chief Commercial Officer of Aurora Biotechnologies. Charles has a well rounded past, having spent many years in the lab automation product division of Beckman Coulter as well as the investment banking industry with CIBC Oppenheimer where he focused on the biotech and pharma industry.

Charles points out that the current pharma model of automated drug discovery is based on the need to generate a large number of leads, to feed multiple therapeutic programs, hopefully eventually resulting in multiple new chemical entities hitting the market each year. The automation and informatics infrastructure needed to support and sustain such an approach is considerable, taking a good amount of money and time to develop and support. If, on the other hand, drug discovery were all done via many small biotechs, Charles feels that such companies would not likely be willing to make a similar financial investment in large infrastructure, nor would their program even require an infrastructure of that size. Perhaps more importantly, though, they would not be able to afford the time required to develop and implement a complicated infrastructure. Their corporate time frames are short and they have to be focused on generating science and IP rather than on building an infrastructure that may not pay off for many years.

Charles notes that you can already see examples of the pharma "Hollywood" model today, it's just not gone 100% that direction. Today, over a quarter of the products of the top 20 pharma companies are the result of in-licensed compounds. He refers to this movement as the "democratization" of drug discovery. Naturally, small drug discovery companies still need to do sophisticated science and still value technology that offered productivity improvements, although perhaps on a more personal scale. In this model, Charles thinks it'll be increasingly important to provide scientists with tools and consumables which allow them to "ask and answer" the same types of scientific questions that are explored in big pharma, but without the presence of large, expensive infrastructure. You could envision this being addressed via more pre-packaging of experimental tools. For instance, microplates sold already spotted with appropriate amounts of test compounds together with homogenous assay reagents provided at the proper concentration. A basic liquid handling device and plate reader would be all that was needed to support a moderate throughput screening effort.

The Lab Man would also point out that such a distributed R&D model would only increase the challenge of sharing data. This will heighten the need for products like ELN's that adhere to common standards of data interchange and offer organizations templates for data and terminology that multiple parties can agree upon.

How would this model affect the development of laboratory automation products? Charles speculates there would probably more outsourcing of areas of product development because with the de-emphasis on "big infrastructure" products, it'll be harder to sustain the need for continuous internal presence of certain types of expertise. Even large technology providers like Beckman-Coulter already practice this. In a way, this is just like Hollywood, where a small creative studio outsources special effects work to another company, who may in turn outsource work to model makers or computer graphics specialists. They all come together as a team for a specific project, but then go their separate ways when the project is done. If the "buying" players, i.e. pharma/biotech, are smaller and more decentralized, then the technology providing players also have to minimize their infrastructure investment and become more nimble.

If this sounds like a more uncertain and less stable environment all around, you're right. Ask people in the movie industry, or even those who work now for very young biotech companies. Innovation is driven by the need of all the small players to differentiate themselves, to stand out of the pack. Presumably in the "Hollywood" model, innovative companies would find each other and team up on a project basis, resulting in the periodic sensational product like occasionally comes out of Hollywood - something like the Lion King. Where would R&D money come from? The large Pharma's would still be out there doing marketing, sales and distribution, just like the current large Hollywood studios. They would probably be the primary source of funding for projects out amongst the collection of small R&D biotech's, along with private and public investment money.

So, is your industry "going Hollywood"? Are you ready?

As you read this, The Lab Man is in the Kashmir Himalaya, seeking enlightenment for yet more future blogs. Namaste! Keep reading! Please comment!

Domo Arigato, Mr. Roboto


ALA Spotlight in Your Neighborhood!

ALA Spotlight in Your Neighborhood! The recent ALA industrial automation survey indicated that the speed, reliability and function of laboratory automation tools

The recent ALA industrial automation survey indicated that the speed, reliability and function of laboratory automation tools are no longer the most limiting factor in the use of such automation. The current limiting factors have to do with the challenge of doing science with such tools, such as developing and validating new automated protocols. In response to this information, the ALA has worked together with two leading providers of laboratory automation to put together a series of workshops that focus specifically on the practical matters and challenges of putting automation to work to do good science. This is the new ALA Spotlight Series.

The Lab Man talked to ALA President Professor Doktor Reinhold Schaefer about these events. He indicates that this is a series of 4 FREE workshops to be held this fall in San Diego, San Francisco, Princeton and Boston. Exact dates, locations and program details can be found on the ALA website. The ALA has partnered with Symyx Technologies and Thermo-Fisher to provide a full day of presentations specifically focused on "how-to" aspects of putting automation to work to do science. This will be an interactive, tutorial-type workshop environment to discuss the successes and challenges of transferring and deploying automation and related technologies in the laboratory, in essence, putting automation to work in a real-world bio-pharma laboratory. As with JALA and LabAutomation, the ALA has put together a team to peer-review the workshop content, in this case Faculty Advisors Mark Russo and, of course, The Lab Man. So the attendees' can be assured of a high-quality scientific program, definitely not a marketing presentation.

Reinhold also pointed out one of the very unique aspects of the Spotlight Series is that early registrants will have the opportunity to vote on which presentations they wish to see. This allows for flexibility in the curriculum to change by locale based on the attendee?s needs, wants and desires.

I asked Reinhold how he, as ALA president, sees this series fitting into the organizations strategic plan. He replied that one of the key goals of the ALA is to provide cost-sensitive educational opportunities on a global basis, blending the three distinct but interconnected groups that comprise the ALA: academic and government personnel; industrial technology users; and the technology providing industry. After this inaugural year for the Spotlight Series, he envisions taking the Spotlight Series to other locales around the globe, such as Basel, Frankfurt, Beijing, Mumbai, Dubai and more.

In keeping with the ALA tradition of making events enjoyable, these workshops have been placed close to members' workplaces, because everyone is busy. Breakfast and a full plated lunch will be provided. Together with lunch will be a mid-day session titled: "The World is Flat: Collaborative Science in a Changing Electronic World", which will include an open forum discussion featuring respected scientists trained on the issues at hand in the changing world of enterprise-wide R&D Informatics.

Information about these and any other ALA activities can always be found at the ALA website. Invitations are being mailed, but you don't need an invitation to attend, nor do you need to be an ALA member. The Spotlight Series is free for anyone to attend, although there will be a limit on the amount of attendees which can be accommodated, so best to sign up early - and provide input about the program options. As a special "get to know the ALA" bonus, non-member attendees will be given full member access to the ALA website for three months.

Enjoy the events!

Domo Arigato, Mr. Roboto!

ELNs are Here!

ELNs are Here!

If it seems to you like we've been hearing about the "paperless laboratory" and Electronic Laboratory Notebooks for many years, then you're not alone. ELNs have been long promised but always "about to become practical". Well, that's changing and if your organization isn't developing an ELN strategy, then you're at risk of falling behind the curve. ELNs are here and being implemented by mainstream organizations, not just early "bleeding edge" adopters. To learn more about this, The Lab Man talked to Michael Elliott, CEO of Atrium Research and long-time expert in the field of laboratory informatics.

As to why ELNs are finally beginning to take off, Michael indicates that the key development occurred several years ago when ELN vendors began to develop domain specific products, such as for synthetic chemistry. By focusing functionality on specific domain niches, these products finally offered scientists a tool that they could identify with and could actually use to improve their workflow and productivity, rather than just serve as an electronic repository for data. As these early-targeted domain groups began using ELNs, it got the attention of their colleagues in other domains, and now the implementation is spreading.

For many years, a big concern about ELNs was whether the data format would stand up to legal patent challenges as well as paper notebooks. According to Michael, the question of the admissibility of electronic records in a court of law has now been clearly settled. United States federal rules of civil procedure now give electronic vs. paper records equal weight, provided that proper authentication and integrity checks exist. There has yet to be a court patent challenge involving actual ELN data, but there has been a patent case which successfully used an email as evidence. It should go without saying that organizations using ELNs still must maintain proper record management and retention practices.

The Lab Man would like to think that recent efforts toward data interchange standards (ANDI protocols, the AnIML schema) might have lead to ELN products that make it possible, dare we say easy, to share electronic notebook data within and across organizations. Alas, as so often seems to be the case in laboratory automation, we are not there yet. Michael feels that there hasn't been sufficient push from ELN buyers for standardization, so the vendor community hasn't focused on the use of standards like AnIML. At best, they offer some ELN interoperability among their various domain-specific products, but cross-vendor interoperability has not received much attention. The various ELN vendors are often better at addressing the needs of a given domain group (i.e. biology vs. chemistry), but if an organization chooses the "best" ELN for each domain group, they sacrifice much chance for ELN interoperability across the entire organization. Even if data interchange standards were fully implemented, the lack of common terminology across functional groups and organizations still looms as a large issue.

If (when) your organization begins to consider ELNs, Michael recommends several points. First, is to understand that ELNs do not represent a simple replacement of paper notebooks. ELNs represent part of a larger informatics puzzle. An organization implementing ELNs should have an overall informatics strategy or vision, and should understand their data flows. They need to identify their data-related operational issues and then develop a roadmap to address those issues. Secondly, an organization must have a strategy for change management when actually implementing an ELN (or any automation solutions for that matter). A tool like an ELN is only as good as the amount of data that goes into it, meaning that it must be used by the scientists to be successful.

So, are YOU ready for ELNs? They're coming your way soon, if not already there!

Domo Arigato, Mr. Roboto!

Are Technology Providers Morphing - Update!

Are Technology Providers Morphing - Update!Just the latest example - Amgen Inc. will add to its Bay Area biotech operations with a $420 million cash acquisition of privately held Ilypsa Inc. of Santa Clara. Ilypsa, which is developing non-absorbed drugs for renal disorders, is a spinoff of Santa Clara-based Symyx Technologies Inc. (NASDAQ: SMMX) that raised some $46 million from Delphi Ventures, Johnson & Johnson and other investors. When the transaction is completed -- expected in the third quarter -- Ilypsa will be a wholly owned subsidiary of Amgen.

Are Technology Providers Morphing?

Are Technology Providers Morphing? The other day The Lab Man ran across this headline in C&E News " Duarte & Palo Alto, CA - Calando Pharmaceuticals Inc

The other day The Lab Man ran across this headline in C&E News: "Duarte & Palo Alto, CA - Calando Pharmaceuticals Inc., a majority-owned subsidiary of Arrowhead Research Corporation, has selected Agilent Technologies to manufacture the active siRNA component in its lead RNAi product, CALAA01".  What's this, I thought?  Agilent isn't in the business of manufacturing pharmaceuticals or pharmaceutical components - they make instruments and lab devices.  Well, I was wrong.  Upon digging deeper, I discovered that Aglient purchased Synpro, a contract-manufacturing supplier of active pharmaceutical ingredients, in April of 2006.  The initial reason was to supply oligonucleotides for Agilent's array business, but as this headline indicates, Agilent has broader aims to become a part of the pharmaceutical supply chain. 

Shortly afterwards, I saw another headline: "HOPKINTON, Mass., April 9 /PRNewswire-FirstCall/ -- Caliper LifeSciences, Inc. (Nasdaq: CALP) today announced an agreement with Pfizer Inc.(NYSE: PFE) under the terms of which Caliper's Discovery Alliances Services division will conduct certain in vivo profiling experiments for Pfizer. These will enable Pfizer to explore new indications for some compounds in its research and development pipeline".  Again, my first thought was that Caliper is an instrument/device company, not one that is involved in the profiling of potential new drug compounds.  It turns out that in January of this year Caliper rolled out their new services organization created from the integration of NovaScreen Biosciences and Xenogen Biosciences, so yes - they are now prepared to take an active service role in a niche of the drug discovery process. 

The more The Lab Man looked, the more similar news he found: "Thermo Electron to Present at the 2006 UBS Global Life Sciences Conference".  Biotech or pharma companies usually do such presentations!  Well, through its spate of acquisitions, Thermo Fisher now owns Dharmacon, a provider of RNA oligonucleotides, small interfering RNA (siRNA) and related RNA-interference (RNAi) products and technologies.  They own Maybridge, which designs and produces innovative chemical Building Blocks and Screening Compounds, and provides Medicinal Chemistry for the drug discovery industry.  And they own HyClone, a manufacturer of cell culture media, sera and bioprocess container systems. 

Corporate goliath General Electric has formed GE Healthcare Life Sciences, headquartered in Uppsala, Sweden.  This division produces technology for drug discovery, biopharmaceutical manufacturing and cellular technologies. It also makes systems and equipment for the purification of biopharmaceuticals.  Some time ago, GE purchased Amersham Biosciences.  At the time, there was speculation that GE would not stay in the services-to-drug discovery business, but they have quietly continued to grow that niche, most recently purchasing Wave Biotech LLC including its subsidiary Wave Europe Pvt. Ltd., to expand it's offering of products and services for the manufacture of biopharmaceuticals such as antibodies and vaccines. 

And let us not ignore the Microsoft Digital Pharma Initiative!  During a recent strategic update call with Wall Street analysts and shareholders, Microsoft CEO Steve Ballmer hinted, yet again, about Microsoft's plans. When itemizing future growth opportunities for Microsoft, Ballmer said: "Last but certainly not least is the efforts we're making in healthcare. Some of you probably don't even have it on your radar screen, but I'm kind of jazzed up about what we're doing there". 

So, what is going on here?  It would seem that many of the long-time providers of laboratory automation and technology are in various ways entering more directly into the life sciences product and services stream.  Business must grow to thrive and survive, so is the life sciences niche that opportunity?  Is a likely outcome/goal for some such companies to eventually be acquired by their pharma/biotech collaborators, as was the case with Merck and Rosetta Inpharmatics, or Vertex and Aurora Biosciences?  Or will technology companies morph into services companies and then into drug discovery companies, as in the case of Amphora?    To seek enlightenment, The Lab Man talked with Kevin Hrusovsky, President and CEO of Caliper Life Sciences, about this trend.  Kevin confirmed that The Lab Man is not hallucinating, there is indeed a trend, but he feels that the motivation and goals of companies varies. 

In the case of his company, Kevin says they have no intention of becoming a budding pharma company, or even letting their services business become the majority of their business.  The services business enhances their technology business by serving a proving ground and demonstration platform for their technology, and provides a way for customers to get to know and become comfortable with that technology before buying.  This effort can also spawn new technology ideas and help refine existing technologies since the services lab is essentially using the technology as a customer would.  All of this helps give the company an all-important method of differentiating itself among the competition, and the services program generates revenue as well.  Not a bad deal. 

Kevin indicates that he does know of some technology companies that felt the way to maximize shareholder value was to actually migrate into being a pharmaceutical discovery company.  The disadvantage of that approach, he points out, is that their pharma customer companies may begin to see such a "transforming" company as potential competition and become wary of teaching such a company too much during a collaboration.  He feels that if a technology company takes such a path, they really have to be looking at that direction as an exit strategy, because the valuation of the company becomes dependent (and usually increases) on the promise of the organizations long-term drug discovery future, rather than on the short-term cash generating technology business.  There is no going back once those expectations are set. 

Even for companies whose business goal is to remain a technology company, Kevin feels that the level of partnering between such companies and their customers is higher than ever before, and will continue to grow.  It's a great way for technology providers to fully understand their customer's needs.  The Lab Man would also point out that such partnering arrangements often tend to mitigate the risk to both technology provider and technology buyer. 

On a completely different subject, Kevin has high hopes that Ohio State will overcome a tendency to settle for #2 in the 2007-2008 sports season.  The Lab Man, being a Big Ten alum, wishes Ohio State great success with the exception of contests with the Boilermakers of Purdue! 

 

Domo Arigato, Mr. Roboto! 

 

Is it time for Vista?

Headline for January LabSnap:

The periodic question that many users of Microsoft Windows face is upon us again - to upgrade to the new Operating System (OS) or not?  This time it's Windows Vista, the long-anticipated successor to Windows XP.  For office computers, the choice is generally made by corporate IT groups, and it's usually a conservative choice of hanging back for a while.  For home computers, we're more at the mercy of the market.  The supply of XP loaded computers in the retail chain is drying up, so if you plan to buy a new PC in the near future, your only choice will be Vista.  But what about computers attached to laboratory instruments and automation?  Those PC's often fall into a "gray zone" of semi-support from corporate IT groups and in almost all cases they are in place primarily to run proprietary software for the control of or acquisition of data from an electronic laboratory device.  So the upgrade of existing laboratory computers to a new OS or whether newly purchased systems come with or require the new OS is completely dependent on the compatibility of that proprietary software with the new Operating System, and that of course is in the hands of the provider of that particular technology. 

How does that process work?  To get some insights, The Lab Man talked to Dr. Bob Burger, Staff Software Development Engineer for Beckman Coulter, who is focused on their laboratory automation line of products, specifically their SAMI control software.  Bob has been with the company for 10 years, so he's had the opportunity to live through several of these transitions.  He indicates that how quickly they bring their software into compatibility with a new OS is driven somewhat by customer demand, the need to take advantage of any technical advances contained in the new OS and the potential lifetime of the new OS.  For instance, their SAMI product was originally written for Windows NT.  They subsequently skipped updating to Windows 2000, because WinXP was already on the horizon, there was no demand from their customer base and Win2k didn't offer any technical advantages for their product vs. WinNT.  They still have customers who are happily running NT4, and thus his software group still maintains the ability to run and test software on that version of Windows, even though Microsoft now no longer supports it. 

According to Bob, that first revision of SAMI from WinNT to WinXP consumed several years of staff time, but the effort prepared them well for future OS revisions in two specific ways.  First, they rewrote SAMI in strict adherence to Microsoft XP developer guidelines.  This is supposed to make adaptations to future Microsoft changes easier, at least to the extent that Microsoft follows their own rules.  Secondly, they developed an automated test suite for the SAMI product.  This allows them to rigorously test their product against any new or revised OS with a minimum of effort and generate a report of any potential incompatibility for further investigation.  The Lab Man should point out that such a time investment in preparing for future life cycles of a product is much more likely to occur within more mature technology-providing companies and for products that have a foreseeable longevity. 

Groups such as Bob's that are Microsoft Developer Network (MSDN) subscribers will typically get beta releases of a new OS several years before commercial release.  Those beta releases are quite changeable and are generally only useful in revealing broad directions or changes that might eventually appear.  The release to manufacturing (RTM), or final build of Vista was made available to MSDN subscribers late last fall, about 2 months before commercial release.  So you can see why it can be quite challenging to have a compatible upgrade version of a complex software package ready and available at the same time Microsoft commercially releases their new OS. 

Bob indicates that through occasional early testing in the Vista beta days, followed by more intense testing with the Vista RTM version, they have successfully adapted their SAMI product to Vista.  However, they have not yet begun their own formal release testing process, a more rigorous testing procedure that would be triggered by a business decision to release a new version of the product.  Many laboratory automation users may have the misimpression that companies of the size of Beckman Coulter have literally fleets of software developers to throw at such problems, but in reality these project teams are relatively small - usually 3 to 4 people.  When they do develop new software, such as a Vista upgrade, Bob says that one of their key practices as developers is to "eat their own dog food"!  In other words, they will use the software they develop and use Vista to assure it "tastes good" before releasing it. 

Listen for sounds of contented munching if you happen to pass through Indianapolis! 

As always, your comments are welcome and encouraged!  Listen to the Podcasts!! 

Domo Arigato, Mr. Roboto

 

 

Disrupted or Disruptors?

Disrupted or Disruptors? Headline for January LabSnap:

The Lab Man was reading in C&E news yet another story about the outsourcing of pharma drug discovery activities to India.  On the same page was a report that Schering-Plough has agreed to acquire Organon BioSciences.  In a recent issue of the same publication was an article entitled  "Drug Companies Restructure to Cut Costs", which discussed layoffs at Abbott, AstraZeneca, Bayer and Pfizer.  Clearly the industry is going through a time of disruption and change, and unfortunately that affects many people that we all know. 

Interestingly, when you think about it, those of us involved in laboratory automation are, and have been, agents of disruption and change.  Technology that we help to promote and introduce has altered the jobs and career paths of many people, and sometimes brought