Why purchase a robot?

Why purchase a robot?

A look at why laboratories decide to automate liquid handling

Having written an article entitled ‘Is downtime crippling your lab?’ (Laboratory News, December 2004) we thought we’d take one step back and discuss the robots themselves and why laboratories decide to automate.

The microplate is now a standard consumable in nearly all laboratories. Available in many formats, but most popularly in 96- or 384-well, it is a common sight on the lab bench (Figure 1). Robot manufacturers have exploited this standard format by developing a method of automating the dispensing and aspirating of liquid into the individual wells of a microplate.

Figure 1.

The man-hours taken to manually aspirate and dispense into 96- or 384-wells, time and time again, is extensive as well as being monotonous for the laboratory technician, even with the advent of multi-channel pipettes.

Whilst a robot can take many hours to initially programme, it is quicker, has less potential for error and is impervious to hazardous materials (e.g. radioactive isotopes). Additionally, as there is now more focus on health and safety at work, it can reduce the risk to laboratory workers of repetitive strain injury (RSI) and work related upper limb disorders (WRULD).

Factors to consider
There are simple liquid handling devices that operate on syringe pumps (WellPro, Titertek, Thermo Electron), which can dispense liquids into a microplate, following comparatively simple programmes. Other, larger, robots are able to control motion in an x, y and/or z direction with as many as 1 through 384 channels.

Although the x, y and/or z robots are described here as larger robots, there are differing sizes within this group, which are able of coping with different workloads. The choice is extremely large, from small footprint to robots that will take up the length and breadth of a large bench. It stands to reason that the robot chosen will be suitable for the throughput of the laboratory in question and the budget available.

There are many factors to consider when purchasing a robotic liquid handler, some of which are:
· Choice of sampling probes - fixed tips or disposable tips
· Configuration of tips (i.e. standard and disposable tips of varying sizes, coatings and lengths of tips able to be attached to the robotic head at the same time)
· Volume range
· Expandable deck (should your throughput or protocols change)
· Individual channel control (variable spacing between channels and whether the channels are able to dispense and aspirate at the same time)
· Speed of arm movement
· Motion precision
· Liquid level sensing
· Flexibility of deck layout (the location of reservoirs, microplates, etc.)
· Precision and accuracy
· Carry-over of sample (especially when using fixed tips)
· 21CFR Part II software compliance
· Ability to accommodate test tubes, vials or other containers
· Size and weight of robot

Fixed or disposable tips?
Fixed tips are available on many robotic systems (Tecan, Packard / PerkinElmer, Gilson). The obvious issue with this type of tip is carry over of sample. To prevent carry over, the fixed tips are washed either with a system liquid, which is pushed through the probes into a rinse reservoir, or at a ‘rinse site’ where rinse liquid is aspirated and dispensed through the tips. For more viscous or sticky liquids, additional rinse solvents can be used. Fixed tips can be used time and time again, so might seem like the most cost-effective option. However, to replace a whole array of fixed tips is substantial.

For disposable tips, whilst carry over is not a concern, there is the question of quality, range availability and price. Disposable tips are replaced after each assay, or pipetting function (hence ‘disposable’). So all concerns regarding carry over are eliminated, but there is the cost of replacing them on a regular basis. However, disposable tips are far less expensive to replace than fixed tips, should the tip cause some sort of robot malfunction (or ‘crash’ to use a more technical term!). Alpha Laboratories disposable tips for robots (robotic tips) undergo extensive quality control testing (Laboratory News December 2004) before they reach an end user (Figure 3 below).

There are two different types of robotic tip:
· Non-conductive (clear or ‘standard’)
· Conductive (black)
Both of these tips can be produced with or without filters and/or sterile, depending on the requirement of the protocol being run (Figure 5).

Conductive tips have graphite added to their production, enabling the robot to sense liquid. They minimise the amount of liquid required in a vessel and enable both ionic and non-ionic liquids such as DMSO or methanol to be detected. As the tip is now able to conduct electricity (thanks to the graphite), the robot is able to sense when the tip touches liquid within the microplate, or other receptacle. This means that over-immersion of sampling tips is minimised and improvement in pipetting performance is achieved.


Figure 5.

However, robots with the ability to liquid sense do not have to use conductive tips. If non-conductive tips are used, the robot will become a standard robot, but the benefits of using conductive tips will be taken away.

Adding the human factor
If you are au fait with manual pipetting you may have a few questions regarding the ability of a robot to perform a function that requires skill.

Dead volume is the last remaining volume of liquid, which cannot be aspirated by the robot, as the tips cannot reach the liquid. Yes, this is handled better manually, as a laboratory technician is able to tilt the reservoir to aspirate the very last of the liquid.

‘Touch-off’ is a well-known technique used to knock off any last liquid droplets hanging to the end of the pipette tips. Robots can be programmed to perform this function routinely after dispensing liquid into a microplate or receptacle. Whilst it is another command that will need to be programmed into the robot, it will save on reagents and increase the accuracy of the assay.

Manual pipetting techniques allow the skilled laboratory technician to decide on the pipetting speed required (e.g. high for small volumes, low for more viscous solutions). But the robot manufacturers have thought of it all! Some of the more advanced robots on the market can be programmed to aspirate and dispense at different speeds, at every step along the way.

What’s in a tip?
Other questions that you might ask are such things as ‘what’s the difference between a robotic tip and a manual pipette tip?’ Good question. Manual pipette tips are manufactured to a high standard, but robotic tips have to have a slightly higher quality control procedure.

If a tip is warped (bent), on a manual pipette, the user can correct for the tip being warped and ensure the pipette is aspirating or dispensing into the correct well of the microplate. However, if a robotic tip is warped, the robot will carry on completely unaware, and could aspirate or dispense into the incorrect well.

Short is where there is not enough plastic (polypropylene) to completely form the tip. The tolerance for short in a robotic tip is much lower than that for a manual tip.

Another quality control point is flash. This is where a ‘tag’ of polypropylene has been left on the tip from the injection moulding process. Again, the tolerance for a robotic tip is much lower than that for a manual tip.

Why are the tolerances much ‘tighter’ on robotic tips than for manual tips? Because a user can correct for slight imperfections in a manual tip. If the tip has not loaded on a manual pipette (due to a short or flash), the user will push it onto the tip cone harder (or throw the tip away). If the tip is slightly shorter (due to a short), the user will lower it further into the microplate. A robot cannot make choices on an individual tip-by-tip basis. It will follow the programme it has been set, regardless of whether the tip has been picked up, or if it has not yet met the liquid (not so in conductive tips as they can ‘feel’ the liquid).

And finally…
From choosing the right robot for your laboratory to choosing the correct consumable for your robot, there are many decisions to be made. The safest way to spend your fiercely guarded budget is to ask for referrals. See the robot in operation, talk to other users and sample the consumables before you buy.

Hopefully your days with your robot will decrease your frustration in your workload and allow you headache-free days to duel with other more pressing tasks.

By Key Pemberton, Alpha Laboratories