April 12, 2013 by Kevin Keras

Who’s Minding The Store?

It has been said that the French love Jerry Lewis.  Books have even been written about it (well, at least one book).store   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 Twistetwister iir II or the PAA KiNEDx or even dedicated plate stackers like the Thermo FisherRapidStak.   Many plate reader companies (Molecular DevicesBioTekBMG 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 froIncubator_Family-09-2011_02_056bb39b14InHeco, which can be stacked on top of each other as well as recirculating fluid locaThermal-Plate-Stacker-Part-STKRtors 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 recepicoservent 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.

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April 9, 2013 by Kevin Keras

Is it safe?

It’s been over 35 years since the movie Marathon Man came out and I still have a fear of dentists.marathon-man   That imagery has nothing whatsoever to do with the topic of this blog, but the title reference was too good to pass up…

Everybody who works in a research lab no doubt has had to go through a mandatory lab safety course or certification.   Companies provide such training both to ensure the safety of their employees and processes as well as to avoid future litigation should an accident occur.    What is not always as clear is how to ensure the safety of visitors, or in the case of instrument support, Beyond providing lab coats and safety goggles, there are a couple of basic precautions that can be taken to ensure the well being of visitors and support techs;

1) Contact Person – all visitors should have the phone and email info for an employee who has been through a company approved safety training program.  Visitors should be required to seek out this person for any concerns they have prior to conducting their worChemical Spill Cleanupk, or in the event of an emergency.   Also, make sure you have the techs emergency contact (work and personal) info in the event that person requires medical attention.

2) Disclosure – Make sure you inform the tech of any biological or chemical hazards regarding the instruments.   Point out instrument decontamination certificates and give direction on how to dispose of wastes (chem wipes, q-tips, wear items, gloves, lab coats).  Also let them know your protocols for dealing with reagent spills or exposure.

3) Evacuation Instructions – Let the tech know how to exit the building inevacuation the event of an emergency.   In addition to typical lab accidents, in today’s world that could also include fire alarms, terrorist attacks, workplace violence).  Point out any per-determined ‘rally point’ once out of the building.   Also, let them know how to re-enter the building or sign out if they do not return so they can be accounted for.

4) Facilities Support – Never let a visiting tech hard wire equipment to your facilities electrical junction boxes.  If such a need arises, have your own knowledgeable facility personnel on hand to disconnect power and supervise all work.   Same goes for plumbing high pressure air lines or water lines.

5) Basic Safety Training – make sure the tech has received basic lab safety training from their employer.  Ask in advance for them to bring a certificate of such training, specific to the visiting tech.

With a little bit of extra consideration, it is  easy to ensure the safety of lab visitors.   And, it your service tech looks even remotely like Sir Laurence Oliver in the photo above, don’t be surprised if he or she incessantly asks,  “Is is safe yet?”

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April 5, 2013 by Kevin Keras

A Robot By Any Other Name…

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 thTecan EVOe 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 systecaliper-staccatoms 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 BioPAA 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 twister-7900cylinder 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.   Industrialbroken_robotrobots 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.

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April 3, 2013 by Kevin Keras

Have I Got A Tip For You…

the-graduate

“I want to say one word to you. Just one word.  Are you listening ? Plastics.” - The Graduate, 1967

Automated liquid handlers are very quickly (if not already there) becoming commodity products.   While every liquid handling manufacturer claims certain features or twists on how they do things, ultimately they all do pretty much the same thing…suck and spit (keep it clean people, we’re running a blog here…)  One sure sign of ‘commoditization’ is when third parties begin to offer accessories that compliment or compete with a particular product and in the case of liquid handlers,  that most commonly means disposable pipette tips.

Wondering if there any performance or reliability issues associated with the use of third party tips? tips To be sure, original equipment manufacturers (OEM’s) test and warranty their products using tips that they manufacture.   It is reasonable then for them to discourage the use of third-party tips insofar as performance guarantees are concerned.   Additionally, most of the OEM’s have made significant investments in the creation and maintenance of plastic injection molds that they or their supplier uses to stamp out their tips… so there is of course an understandable financial desire for them to want customers to purchase only OEM tips.

Insofar as periodic maintenance is concerned, end users should note that if they are performing routing CV checks (either gravimetrically or via a dye test), the tester needs to consider that differences in accuracy or precision may be affected by badly formed tips but that holds true regardless of who makes the tip.

However, it is not reasonable for an OEM to claim that the use of non-OEM tips “might” void the equipment’s warranty.  That’s a bit of a scare tactic that upon further reflection speaks more directly to lost consumable revenue than the fear of tip induced hardware failure.   I mean, if a tip gets stuck on a mandrel instead of getting shucked, I guess yeah, you could experience a crash that could damage the liquid handler.  Crashes do happen but such occurrences are rare once a tip is in production as most of the third-party providers I have dealt with have very stringent QC programs.    If you want to err on the side of caution, consider using OEM tips for new purchases and evaluate third-party tips once the warranty expires (usually 1yr).

Looking for alternative tip providers;

Corning/Axygen -   Agilent/V11, Beckman Coulter, BioTek, Caliper/PE, Dynamic Devices, Hamilton, Molecular Devices, Tecan, Qiagen

Labcon - Beckman Coulter

Phenix Research – Agilent/V11, Beckman Coulter,  Caliper/PE,  Eppendorf, Molecular Devices, Tecan, Qiagen

Thermo Fisher/Molecular BioProducts – Agilent/V11, Beckman Coulter, BioTek, Caliper/PE,  Molecular Devices, Tecan, Qiagen

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March 29, 2013 by Kevin Keras

DIY in the Lab

Things break in the lab. Here’s how to protect your equipment, and what to do when it stops working.

By Jeffrey M. Perkel | March 1, 2013
 
tl_files/labsquad/blog_images/diy/labtools-2.jpg

With NIH funding fewer than 20% of the research grant applications received in 2011 (the most recent data available) and little hope for improvement in the coming year, researchers must squeeze what they can from every dollar. For some cash-strapped labs, that means buying used instruments instead of new, keeping equipment running long past its warranty, and jerry-rigging existing lab gadgets that might otherwise be scrapped.

When such equipment inevitably fails, it puts yet another strain on already tight budgets. Researchers facing service calls costing hundreds of dollars an hour may feel obliged to delay repairs, only to find that a service tech may not be readily available. Even in the lab, time is money.

There is an alternative. Lab workers armed with a bit of mechanical know-how and some basic tools can sometimes tackle repairs and problems themselves. Not every repair can or should be handled in-house, but those that can will get the lab up and running quickly and cheaply. The Scientist spoke with equipment repair technicians and core facility directors about the kinds of repairs that researchers can and cannot do on their own, and some obvious, but oft-ignored, steps they can take to avoid problems in the first place. Here are their suggestions.

1. RTFM (READ THE F**KING MANUAL)

Like cars and computers, laboratory equipment almost always comes with a manual (either printed or as a PDF). And, as with cars and computers, researchers often toss those manuals in the trash or “file” them in a drawer. Here’s a better idea: as they say on the interwebz, RTFM. Manuals outline recommended maintenance and cleaning schedules, provide troubleshooting tips, and demystify error codes. (Lane Smith, President and Senior Engineer at Phoenix Technical Services, an equipment repair company that serves the University of Mississippi, suggests storing manuals together in a safe place, or as PDFs in a common folder on a lab computer, for easy retrieval.)

The maintenance suggestions these manuals lay out may surprise you. Rebecca Wood, co-owner and vice president of Southern Medical Services, a medical and lab equipment repair firm that serves south Texas, notes, for instance, that some vacuum pump manufacturers specify in their manuals that vacuum oil should be changed after every use. Yet many researchers reuse the oil until it gets dirty—a practice that could potentially cost the lab big bucks. “If you had a vacuum pump that quit and you sent it in for repair and it had black gunk in the oil, they would say you’d voided your warranty,” Wood says.

2. Clean up once in a while

An ounce of prevention is worth a pound of cure, they say, and that’s certainly true in the lab. Dust accumulates on computer parts, ice accretes inside freezers, and carbon dust builds up inside centrifuges and stir plates. Taking care of these issues before they become problems can save a lab some money in the long run. “If you use a [centrifuge] rotor, make sure it’s cleaned afterwards,” says Craig Folkman, a field service engineer atBioNiQuest Lab Services in Danville, Calif. “Make sure O-rings aren’t cracked, and change them as necessary. If there’s a spill, clean it up, don’t let it sit there.”

For mechanical devices that use brush-based (as opposed to induction) motors, such as vortexers and microcentrifuges, Smith recommends investing in a small vacuum cleaner to clean out the carbon dust. (Smith notes that replacing a worn set of motor brushes is a relatively simple task that researchers can do themselves. For one of his techs to make a lab call would cost $200 for an hour of labor plus the brushes ($20–$50 for a set), not to mention travel time.)

Invest in a can of compressed air to clean computer fans and cables, or tracks on liquid handlers. And clean the air filters on lab freezers regularly (they are usually easily accessible on the front of the instrument). “These are fairly expensive pieces of equipment, and some scientists will have their entire research life in these things,” Smith observes. Cleaning or replacing the filters will keep the compressor working properly and prevent it from overheating.

Another easy bit of maintenance: Defrost freezers regularly. “Try to do it once a year, because you will either do it on your own schedule or on the instrument’s—at 2 a.m. on a Sunday morning.”

3. Establish a maintenance schedule

“My feeling about lab repairs is really trying to avoid them,” says Tim Hunter, Director of the Advanced Genome Technologies Core at the University of Vermont. Hunter recommends lab managers ensure that each piece of equipment be kept on a routine maintenance schedule (often outlined in the operator’s manual).

For instance, in his facility, one worker’s job includes tracking the background signal in the lab’s real-time PCR machine, to make sure the instrument is operating correctly. Another bleaches fluid lines in the array reader between runs to minimize cross-contamination concerns.

Another commonly overlooked task, Hunter says, is defragmenting the computer hard drives attached to lab equipment. Hunter suggests doing that monthly. “[These are] things that people take for granted and just don’t check, but [that] can really impact things when you least suspect them.”

Wood recommends copying and laminating the schedule for each piece of equipment and affixing it on or near the machine, so that everyone in the lab knows what needs to be done, and when.

4. Build a basic lab-repair toolkit

Charles T. “C.T.” Moses, an independent consultant in Framingham, Massachusetts, has been offering seminars on laboratory equipment repair throughout the Northeast since 2004. The handout for his seminar includes a suggested laboratory tool set for taking on most basic repairs (see also: www.chastmoses.com/tools.html). To wit: Flashlight; multipurpose screwdriver (slotted and Phillips); small vise grips, needle-nose pliers, and side-cutter pliers; a small crescent wrench; small clamps; scissors; measuring devices (scale, tape measure, or ruler); small hammer; pocket knife; multimeter; polarity tester (to test electrical circuits); and a lockable tool box.

Other items you might want to have on hand are lubricants (e.g., oil or WD-40), compressed air, a set of American and metric Allen and socket wrenches, a drill, and electrical tape.

5. Try the obvious

When something goes wrong, the most obvious solution sometimes is the right one. So, if a piece of equipment suddenly stops working, make sure it actually is plugged in and that the outlet is working; even in the lab, plugs come loose, fuses blow, and circuit breakers trip unexpectedly.

Smith recommends doing a quick and commonsense “self-assessment.” For instance, if the −80 °C freezer is suddenly warming up, did anyone recently perform an inventory during which it was left open? Ditto for the cell culture CO2 incubator.

Next, see if restarting the instrument and/or attached computer solves the problem. Or, if it is a mechanical device, see if you can identify something obvious, such as dirt in a track or hinge, which might be causing the malfunction.

If the problem persists, write down any error codes or messages you see, as well as what you were doing when the problem occurred. For instance, if an autoclave stops working, where in the cycle did it halt? Also, see if you can figure out where in the instrument the problem is occurring. “The easiest thing to do when troubleshooting is to cut your problem in half,” says Folkman. For instance, suppose your HPLC isn’t working; see if you can determine whether the blockage appears to be between the buffer reservoirs and the pump, between the pump and the column, or in the fraction collector.

Even if you end up having to call in a repairperson, such information can save time (and thus money). “If you have an error message, instead of saying ‘I’m getting this diagnostic

,’ if you can say ‘I tried this or that,’ that makes it easier for us. . . . We can know exactly what the issue is.”

6. First, do no harm

If you do decide to open up an instrument to attempt a fix, Smith recommends following the physicians’ creed: First, do no harm. Put another way, make sure you can put back together that which you have taken apart.

Use a cellphone camera to take pictures of wires and instrument settings so you know where they go and how they were arranged. Moses suggests using a piece of white paper, marked to indicate the front and back of the instrument, and taping screws on the paper in approximately the positions from which those screws came, “so you know more or less how it goes back together.” (Oftentimes, instruments may use different screws in different positions, so this kind of information can be invaluable.)

To do no harm also means to protect yourself, says Moses. That means powering down and unplugging equipment before opening it, and putting your left hand behind your back before plugging it back in and turning it back on. That latter point, he says, is an “old electrician’s trick” that “helps prevent shocking your heart should your repair leave a loose wire inside the machine.”

Deciding what can and cannot be repaired in the lab must obviously be done on a case-by-case basis. But as a general rule of thumb, repairs that are covered in an instrument manual’s troubleshooting section can probably be attempted in the lab, such as changing the bulbs on a spectrophotometer or replacing the brushes on a microcentrifuge. Instruments like stir plates are easily fixed, says Moses—often a drop of oil at the point where the motor shaft emerges from the motor, called the bushing, is all it takes.

Instruments that are under warranty or service contract probably should not be repaired in-house, as doing so might void the warranty. Very heavy equipment, very expensive equipment, equipment with precise tolerances (such as a microscope), or equipment involving high voltages, lasers, and so on, probably should be left to experts as well. So should equipment with obvious charring or burning, Moses says, as these might require special expertise in measuring and monitoring electrical circuits.

7. Know when to call for help

When in doubt, it never hurts to call the manufacturer or a third-party repair company. Smith says his company will often offer advice gratis over the phone, and so will most instrument vendors. “I have rarely come across a manufacturer that will not answer simple questions on the phone,” he says.

In some cases, you can purchase a part, like a hinge or a circuit board, and have technical support walk you through the installation process. But make sure the repair doesn’t cost as much or more than buying new. Moses recommends checking the manufacture date on equipment to see how old it is (and thus, if it makes sense to repair it). Circuit boards and electrical components often contain a four-digit code in the form YYWW. For instance, 9613 means the component was built in the thirteenth week of 1996; 0744 means the forty-fourth week of 2007. Though such information will not give a precise manufacturing date, an instrument obviously must be at least as new as its newest component.

But before you do anything, see if you cannot at least identify what is wrong before calling in an expert. By figuring that out you can give the technician the most accurate information, thereby saving him time and you money. Just as practically, you can learn what to do differently moving forward.

“By opening [up a piece of equipment] you can be aware of what happened and what not to do in the future. We don’t want this to happen again,” Moses says. 

Originally Published on March 1, 2013 at:  The Scientist.com

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March 26, 2013 by Kevin Keras

Nervous…System Support

My last post about standardization and open source scheduling software for integrated systems got me thinking more about the post-sales support sidon knottsde of those systems.

As many of you know, systems can be very expensive so end-users are making critical decisions on behalf of their employers, both on how well their money is being spent and what are reasonable expectations as to when the system will begin to show a return on that investment.    There is always concern about that ramp up time and the problems you may encounter along the way, so the question of warranty becomes very important to the lab manager or principal user of the system.

Most system integrators go through a very similar process regardless of who the end user is.   It generally all starts with a customer needs assessment, whereby a sales mabiocelnager (usually accompanied by an Application Scientist) asks a number of questions prior  to generating a system concept proposal.   While it may seem tedious to the end-user, (I know what I want, why can’t these people just give me their quote?) this is a critical step in ensuring long term success.   I have been involved in a number of situations where a customer had budgeted hundreds of thousands of dollars but could not provide a single manual method they wanted to automate.    Not good.

Weeks (more like months) after  the system is designed/proposed and agreed upon/purchased by the customer, a date is usually scheduled for a FAT (factory acceptance test) whereby the customer visits the integrator and goes through a “buy-off” checklist prior to shipment.  This buy-off is best done with beckman systemthe actual customer methods (minus real chemistry) to ensure that the system performs as agreed upon prior to shipment.   Remember, shipment means breaking down the system and packaging so that it can be “re-integrated” yet again upon arrival at the customer site whereupon it goes through the SAT (site acceptance test) which is basically the  same buy-off as the SAT, albeit with actual chemistry.   Once completed, you get a handshake (maybe a hug if it goes really well) and “TA-DA !”you own the system.

Most integrated systems come with a one year warranty.  This can mean different things to different integrators but in my experience, entails parts and labor only (travel is nostaublit included).  It also does not include operator induced failures like crashing a robot into an instrument.  In general, most systems include a fair number of third party instruments that the integrator does not manufacture and they don’t make a lot of money providing them.   These instruments come with their own warranties (usually 1 yr) and the integrator almost always passes these on to the end-user, acting as the first point of contact if a failure occurs.   Since the instruments can often reside at the integration firm for several weeks prior to FAT,  it is important for end-users to understand their warranty…’what is covered?’, for how long?’ and ‘when does the clock start ticking (upon shipment, acceptance)?’.

As mentioned in prior posts, an extended warranty for an integrated system can often cost 10-15% of the purchase price of the system.   Some integrators offer an incentive (discount) if you purchase such an extension with they system, or prior to expiration of the standard one year warranty.   Should you choose that option?

In short, the answer is no and I will tell you why.   Let’s assume we are talking about a $350K ELISA system that includes a robot mover, bar code reader, liquid handler, plate washer, ambient storage hotels and plate reader.    Those majorbeckman systemcomponents probably account for less than 50% of the price of that system.   The remainder is comprised of  things that don’t wear or break (system tables, enclosures, scheduling software, PC and …labor).   That last one is a biggie.    Integration is hard work and proper design, build, programming and testing prior to  SAT can include hundreds of person-hours.  That is commonly referred to as NRE or non-recurring engineering.   A warranty for such a system could cost upwards of $50K, or more (not including travel) but you really should only care about the instruments…not the other stuff.

So, if you are faced with a decision regarding extending the warranty of your integratedautomateitsystem…push back.  It’s pretty easy to determine the list price for each instrument in a system and request a contract that is based on just those costs.   You could also go directly to each manufacturer and request contract pricing on their product only.   If that is too time consuming or a management hassle you don’t need, you may want to reach out to one of the major MVS (multi-vendor services) providers (ThermoPEJohnson ControlsAgilentGE) or smaller ISO (independent services organizations) like The LabSquad.

Don’t be nervous about system support…be informed.

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March 22, 2013 by Kevin Keras

SiLA Love Songs

Time to talogo_silake 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 establishepolarad 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 systemsMicrosoft.Net 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.

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March 21, 2013 by Kevin Keras

Is your instrument A-OK? If not, you may want to fix it PDQ (or you may be SOL) – LOL!

Is there an acronym for excessive use of acronyms?  It seems every industry has a long list of abbreviated jargon to capture the essence of what is important to their needs…and the life sciences industry is no exception.   Below are a just a few of the many acronyms that we encounter in our daily support of lab instruments and some brief definitions.

OEM – Original Equipment Manufacturer, generally the name of the company who sold the instrument.  However…there have been numerous mergers, acquisitions and bankruptcies over the past decade or more so your BioRad thermal cycler might be sitting on the bench with an older model with an MJ Research logo, or your Zymark Twister robot could now say Caliper Life Sciences (which is now Perkin Elmer)…you get the idea.

MVS – Multi-Vendor Services, a generic term that describes a single services provider who works across multiple vendor brands and product lines.   Giants include Unity Lab Services (Thermo), PE OneSourceAgilent, Johnson Controls and GE Healthcare.

ISO – Independent Service Organization, anyone other than the OEM.  Typically a local provider who works directly with customers or acts as a sub-contractor to MVS’s.

PM – Preventive Maintenance, sometimes called Periodic Maintenance.  A pro-active service performed prior to instrument failure designed to catch wear items before they escalate into more costly failures resulting in downtime.

MTBF – Mean Time Between Failure, a spec provided by some OEM’s that statistically predicts instrument reliability.   Failures are generally defined as abnormal occurrences that cannot be easily remedied by an operator and render the instrument or system inoperable.

MTTR- Mean Time To Repair, the average time required to repair a failed instrument or system.   Total number of failures / total time instrument/system is unavailable for intended operation.

IQ – Installation Qualification, documents that the correct instrument was received and installed properly. IQ can be performed by the user or the vendor (typically both during the site acceptance of a device or system).

OQ – Operational Qualification, tests that the instrument meets specifications in the user environment. OQ can be performed by the user or the vendor.   Some instrument include simple diagnostic routines that can be run by users, however a number of such tools are password protected or visible only to service personnel.

PQ – Performance Qualification, tests that the system performs the selected application correctly. PQ must be performed by the user, or in the case of some GxP or CLIA labs, a third party that provides hard data.

CV – Coefficient Of Variation (not your curriculum vitae, or resume),  a normalized measure of dispersion of a probability distribution.  Insofar as labs are concerned, this is generally a reference to unexpected errors across a microplate.   The resulting errors or outliers may often be traced back to liquid handling or pipetting performance.

GLP 0r GMP – Good Laboratory/Manufacturing Practices, a set of standard operating procedures (SOP’s) to ensure the uniformity, consistency, reliability, reproducibility, quality, and integrity of chemical (including pharmaceuticals) non-clinical safety tests.   Insofar as automation of assays is concerned, these SOP’s may contain periodic OQ & PQtesting of individual instruments, using NIST traceable tools and including analytical date (where applicable) .  Techs working in such labs may be required to show tool certificates prior to beginning work and produce validation results.

CLIA – Clinical Laboratory Improvement Amendments, any facility which performslaboratory testing on specimens derived from humans for the purpose of providing information for the diagnosis, prevention, or treatment of disease or impairment, and  for the assessment of health.   As with GxP above, CLIA labs follow stringent SOP’s regarding instrument support or verification, often requiring certified documentation (audit trails).

Did I forget any?  Don’t be shy, let me know.   TTFN!

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March 18, 2013 by Kevin Keras

Is it a System or is it a Liquid Handler?

Remember Razzles? – ‘is it a candy or is it gum?,” so the TV commercial went.   (I actually razzlessubmitted a contest entry calling it  ‘Ghandy…a peaceful coexistence of seemly incompatible delights.’  Not bad for 9yrs old and still waiting on a reply.

Servicing liquid handlers can be a lot like Razzles in that you start out thinking you are working on one thing only to show up and find out that you have something else going on.

System Types:

There are essentially three types of plate based automated systems commonly found in life science research labs.

Robot Centric – A robot arm (manipulator) delivers all consumables to/fropaam a variety of plate based instruments and storage devices.   While many such systems include a liquid handler, they along with other instruments are controlled via a separate scheduling software that oversees the assay steps and ensures proper timing.   Common examples are Hi-Res Biosolution ACell , PAA automate.it,  Agilent BioCel and Caliper (PE) Staccato.

Distributed Robots – Similar to above, except that there are multiple robot arms connected via a conveyor belt or other plate transporter.  Each arm is dedicated to a small number of instruments which each carry out the assay in a sequential (first station to last) fashion.  Again, one or more liquid handlers may be present in the system however they contain programs that are initiated 

dim4

by a higher level scheduling software.  Such systems were very popular in the pharma industry (Thermo Dim 4, Zymark Allegro) rush to process more compounds per day (HTS and uHTS) looking for new chemical entities, but nowadays you be hard pressed to find many survivors still in operation.

Liquid Handler Centric- In this instance, the liquid handler is the heart of the system, which is to say, the liquid handler software runs the assay (no higher level scheduling software).   A large number of these types of ‘systems’ consist of just the liquid handler, by itself, simply carrying out pipetting operations.   However, as many mainstream liquid handlers now include robotic gripper capabilities, these devices start to be 

evo-system

stretched into more capable systems that automate more of the assay freeing up lab personnel for more high value operations.   The plate gripper can load/unload consumables for multi-plate runs or can deliver consumables to shaking, heating, cooling or waste locations on the liquid handler deck or may move them off-deck to plate readers, washers, centrifuge, incubators, thermal cyclers, reagent dispensers or storage devices.   Examples can be see from well known vendors such as Beckman CoulterTecanHamilton RoboticsAgilent and Perkin Elmer.

Conclusion – when exploring your options for servicing a liquid handler, be sure to consider any peripheral equipment attached to that device.   If the end-user expects their entire system to PM’d during a routine visit, the service tech may be either the bearer of bad news or a well prepared and valued service provider.

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March 6, 2013 by Kevin Keras

Liquid Handling Questionaire (‘questionaire’ is French for…questionaire)

If you or your lab currently use liquid handlers, or are planning to purchase liquid handlers please take a few minutes and fill out this labX survey.

(click on the image below and you will be redirected to LabX)

tl_files/labsquad/blog_images/liquid_handling_questionaire/labx-survey.jpg

Looking to buy a liquid handler?   Try www.UsedLiquidHandlers.com

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