April 12, 2013
It has been said that the French love Jerry Lewis. Books have even been written about it (well, at least one book). I would not presume to question French culture…however even Jerry’s old partner Dean Martin sang “Everbody loves somebody sometime…”
Still, when French scientists need to automate ‘cell culture‘ and other time or temperature sensitive assays, they (and researchers from many nations) require automated storage devices (…all that for a ‘store’ reference?)
One of the more common instruments that enable extended walkaway time (the ability to automate multiple plate runs of any given assay) is the automated incubator. Actually, the term incubator is a bit on a misnomer as these “plate hotels” can have a variety of temperature and/or humidity ranges that enable their use in a wide variety of assays. To further complicate that definition, said plate hotels can also be used to store plate lids, tip boxes and tube racks.
Ambient – Perhaps the most common of all plate storage devices, ambient hotels can be as simple the removable storage racks found on plate mover robots such as theCaliper/PE Twister II or the PAA KiNEDx or even dedicated plate stackers like the Thermo FisherRapidStak. Many plate reader companies (Molecular Devices, BioTek, BMG Labtech…etc) also offer dedicated ambient stacker options. Additionally, Liconic, , Agilent,Hi-Res Bio and Thermo Fisher(Kendro/Hereaus) also offer stacker hotels with built-in elevators/plate presenters that are also used in their temp/humidity controlled devices. Hi-Res Bio also offers the PicoServe for robot arm access. For the most part, users only need to consider if their assays require random access of individual plates or stacked storage (one plate on top on another). Stacking plate racks follow what is known as a LIFO or Last In, First Out paradigm. This is great for empty plates that will be fed into a system for simple tasks such as plate replication or reformatting. Some folks even use this as a means of eliminating lids, as the plate above acts as the lid for the plate below – top plate is a blank). Random access racks (individual plate holders) are great for assays where you need to treat each plate uniquely such as hit picking or ELISA. Plate racks come in portrait or landscape orientation and some devices allow for bar code verification or delidding options.
Heated/Cooling – Options start to become more limited when you need environmental control. Small batch options include self-contained single plate devices from InHeco, which can be stacked on top of each other as well as recirculating fluid locators fromMéCour. MéCour also offers a recirculating fluid jacket for Twister II racks. For more than a handful of plates, there are three well established providers;
- Liconic – For well over a decade, this little juggernaut from Lichtenstein has created a formidable offering of products, all designed for liquid handler or robot manipulator access. They also offer ambient hotels that utilize many of the core components used in their environmental models. The range of products covers just about any application you can come up with! Just a word of caution, depending upon the age of the instrument, you may find that there are design variations that can make post sales support challenging.
- Thermo Fisher -Thermo acquired Kendro in 2005 and carried on the Cytomat/Heraeus (and Sorvall) product lines. Originally, the Heraeus products were co-developed with Liconic and shared many common components and needs, but more recent products are of a completely new design.
- Hi-Res Biosolutions – a relative newcomer to storage, but a very impressive line of products ranging from the 8 position Plate Chill cooled racks to high-capacity plate or tube storage.
End users, OEM’s and system integrators have a wide variety of choices when it comes to extending assay walk-away time. The French may indeed love Jerry Lewis but researchers love having time to perform higher value tasks due to the reliability of plate storage devices.
April 5, 2013
A number of lab systems incorporate robot arms to manipulate consumables (plates, lids, tip boxes, troughs). Robots, insofar as lab automation is concerned, can be broken down into three categories:
Liquid Handling Robots- Ten years ago or more, if someone in the lab was talking about a robot, chances are they meant a liquid handler. Not surprising, since most liquid handler are essentially XYZ robots. However, unlike their more generic cousins which are used in industrial manufacturing applications, these robots have evolved into application-specific workstations. That is to say, they come pre-tooled with everything that is needed to perform plate preparation applications. Even their software is specific to these applications.
Industrial Robots- When moving consumables off the liquid handler deck, to peripheral instruments (readers, washers, storage…etc) a number of lab systems are built around industrial robots from established companies such as Staubli Robotics,Mitsubishi Electric and Epson Robots. These robust and increasingly affordable robots were once the exclusive purview of industrial assembly lines or semiconductor manufacturing. Smaller sizes and lower costs have resulted in widespread adoption by integrators such as Hi-Res Bio, PAA andCaliper Life Sciences (PE). Out of the box, these generic devices are not much more than building blocks – requiring tooling (gripper hands/fingers, storage devices, sensors and a good deal of programming and teaching to make them manipulate lab consumables. However, once tooled up and programmed they are reliable workhorses that require little, if any maintenance.
Plate Mover Robots – Zymark (now Caliper/PE) was one of the first companies to come out with robots dedicated to plate movement. The Twister plate loader was essentially a miniature version of an industrial cylindrical robot – meaning it’s work envelope was cylinder shaped instead of rectangular, like XYZ robots. What made this robot unique is that it came with microplate gripper and fingers, as well as removable plate storage racks. My good friends Rick Bunch and Brian Paras did a masterful job of marketing this product (over 3000 were sold) which became the de-facto standard for loading instruments for nearly a decade. Soon, improved varients emerged such as the Hudson PlateCrane EX, Zymark (PE) Twister II, Thermo CataLyst Express and more recently Peak Robotics(now PAA) KiNEDx/ProNEDx/BiNEDx and Precise Automation PreciseFlex all capable of tending to several instruments (Twister was ideally dedicated to one instrument). Additionally, unlike industrial robots which generally come with sophisticated controllers with multi-tasking operating systems and proprietary programming languages containing huge command sets with an endless syntax permutations, plate mover robots come with build in controllers (no separate box or umbilical cords) and a concise command set that is optimized around moving microplates. Finally, the platemover robots have found dual use as instrument loaders as well as becoming the hub of many integrated systems just like their industrial counterparts noted above.
Last words: Both liquid handling and plate moving robots are well within the means of many labs both in terms of price and functionality as well as ease-of-use. Industrialrobots are best left to those with deeper engineering resources or professional integration firms. Since this is a blog about support…the same holds true in that many labs or third parties are capable of supporting liquid handler and plate movers however, not many (including integrators) are truly capable of services industrial robots. That is a task best left to the robot manufacturer.
March 22, 2013
Time to take a break from talking about instrument support and wax philosophically about a bigger support challenge – integrated systems. A colleague asked me my opinion of the SiLA, a consortium that is creating standards for lab automation instrument interfaces.
As I understand it, the folks behind SiLA have a business model that will define these interface standards and then presumably charge instrument manufactures for the privilege of claiming “SiLA Compliant,” or some such declaration. I have to admit that my knowledge of this model is sketchy at best, and the SiLA website does not really lend much insight.
This seems a bit like putting the cart before the horse to me. That is to say, the instrument interfaces are fairly useless without a higher level scheduling software that manages assay workflow, instrument status and data.
In the 1980′s and 90′s, there were many such products from well established system integrators such as RoboCon (acquired by CRS Robotics), CRS Robotics (acquired by Thermo Electron, who merged with Fisher Scientific), Scitec (acquired by Zymark), Zymark (acquired by Caliper, who merged with Perkin Elmer) and Velocity11 (acquired by Agielnt) — do you sense a theme here? All this M&A activity happened during the HTS and uHTS craze. Once that goldrush ran it’s course, it became clear that system integration is difficult in a public company. It’s hard to take a 16-20 week design/build/install model and cram in into a quarterly revenue model. Systems needed to become smaller, more standardized and less expensive.
Nevertheless, each integration company created their own assay management and scheduling software and wrote their own libraries of instrument interfaces. Hundreds of systems were installed and not a single one required the involvement of SiLA or any other instrument standard. One common thread that enabled each of these software’s to succeed was the widespread adoption of Microsoft’s COM, OLE and eventually ActiveX and .NET frameworks. As long as instrument manufactures included automation “hooks” based on the MS framework, integrators had little trouble creating robust instrument interfaces. It’s really not that complicated, as you really just need to be able to initialize, start, stop and report error status for most instruments. Data (from readers primarily) was generally a secondary consideration and not part of the scheduling paradigm.
So flash forward a few years and there are remarkably fewer pure integration companies left. Caliper/PE and V11/Agilent are still out there, but not perhaps as visible as they once were. Thermo Fisher now has a more limited presence as well. To be sure, companies like Beckman, Tecan and Hamilton still build systems but they are primarily liquid handling companies first, integrators second. Really only HiRes Biosolutions,Process Analysis & Automation Ltd. or PAA and Hudson Robotics still fit the pure integrator definition.
It would seem to me that without an Open Source scheduler software standard, there isn’t much need for an Open Source instrument interface standard. Each of the companies mentioned above already have significant investments in creating their device libraries. What is the incentive for them to abandon those interfaces (many of which they charge for) in favor of the SiLA standard? I’m not saying they wouldn’t but I’d like to hear a good business argument for it, other than fear of someone else doing it. In fact, I would imagine that an Open Source scheduler could exist nicely even without SiLA, much as the proprietary schedulers have existed. As users create interfaces to various instruments, they would put them into the public domain for anyone to use…no SiLA required.
A few years back, a number of folks in the Cambridge, MA community came together and started to discuss an Open Source scheduler. About two years ago, Caliper donated it’s CLARA/iLink source code to the University of Wales, in Aberystwyth which can still be found on Source Forge under the name LABUX. Last fall, two MIT students created a similar effort called Clarity. I have not followed either of these endeavors closely, but it seems to me that they could either solidify SiLA or bury it.
My opinion? When I ran the system business at Caliper, prior to the PE merger, I was not a big fan of Open Source scheduling. I knew the investment we had made in our own software and although I knew it had it’s limitations, it was enabling technology that created significant revenue. Still, I saw the LABUX initiative as a way of testing the waters. If an open source scheduling standard did emerge, better that it be something we were familiar with. Additionally, if we could build systems and not have to maintain the software staff to maintain the scheduling software, we could in theory be more profitable (that public corporation thing again). Now, two years removed from that role, there does not appear to be solid consensus on Open Source scheduling or interfaces. I have no stake in the game anymore, so perhaps I can now be a bit more candid and say. I am a big fan of the pure integration model, so I am rooting for HiRes, PAA and Hudson! I still don’t get the whole SiLA thing. Seems a bit… SiLLY to me.
February 27, 2013
The first lab robot was introduced byZymark Corporation in 1982. The Zymate robot was used to move labware between various instruments in a ‘pie’ shaped work area, simulating the same procedures followed by theoreticallyhigher priced lab researchers and their assistants. Fast forward 30yrs and the term lab robot can be further applied to several unique devices;
- Liquid Handlers – XYZ robots that pipette reagents, some can move plates using gripper hands. These devices can pipette in a variety of ways from one single channel, 4-12 channels for row or column work or 96 or 384 channels for whole plate transfers. Some liquid handlers are used as stand alone devices (islands of automation) and can also be found as the central components on larger automated systems which provide extended walkaway time for users.
- Plate Movers – Essentially bench top robots that are specifically designed to transport microplates. Unlike more flexible industrial robots, these units are pre-tooled for handling microplates and come with plate gripper hands and plate storage racks. Plate Movers generally have a simple software interface for teaching plate locations so users don’t have to deal with the vast command sets that come with more flexible robots.
- Industrial Robots – While designed for a host of applications from electrical/mechanical manufacturing to painting, welding and sorting, a number of industrial strength robots can be found at the heart of fully integrated systems. Generally chosen for their extended reach, these highly sophisticated devices use a small subset of their potential for moving plate between storage devices and instruments at slower speeds than might be found in other applications.
All of these devices are approaching commodity status is the life science markets (drug discovery, genomics, proteomics…etc) which means that their prices are dropping and their ease-of-use is increasing, resulting in faster adoption and deployment. And while it may be obvious to most, several of the main reasons for automating lab applications remain constants over time;
- Increased Throughput – process more samples without human intervention. This makes lab workers more productive by freeing up time to work on other critical tasks.
- Repeatability – many lab techs can pipette just as good as any liquid handler, however pipetting is time consuming and its repetitive nature can make it an error-prone operation. Liquid handling robots largely eliminate human variability and human error, resulting in more reliable data (that’s the whole point of an assay, n’est pas?)
- Human Safety – Operator exposure to dangerous pathogens, reagents or radioactive chemistry can be minimized with automation. (think the garlic smell of DMSO to skin exposure…maybe not life threatening, but certainly a potential social stigma…)
- Assay Integrity – While human safety is a major concern for many labs, protecting assay integrity is equally important. Environmental enclosures around automation helps minimize assay contamination due to human interaction
For more information’
- Agilent Technologies
- Beckman Coulter
- Dynamic Devices
- Hamilton Robotics
- Perkin Elmer (Caliper)
- Hudson Robotics
- Peak Robotics / PAA
- Perkin Elmer (Caliper)
- Precise Automation
- Thermo Fisher Scientitic