The eVolving Needs of Quality Assurance

By SGE Analytical Science | Case Study

SGE’s revolutionary electronic syringe provides critical performance when and where it is needed in demanding QA field applications.

Introducing a new method or product into the world of compliance- and quality-conscious life science laboratories is a challenge.  While ultimately appreciative of most technologies that will increase their quality and productivity, these laboratories insist first of all on robustness, proven performance, and ease of integration into their work flow.

Hence, the firm that has proudly developed a new product or method for these laboratories discovers that their work is only half done.  There is an equally critical need for a creative and graceful  solution in the presentation, installation and validation of its new innovation – if it is to gain acceptance by this demanding audience.

This is exactly the scenario in which Wendy Vaccaro, Artel’s Technical Services Manager, found herself in.  The Artel development team had released to the market the revolutionary MVS® Multichannel Verification System.  This new product was designed to set new standards in generating fast, accurate, repeatable and easily utilized data for managing the performance of any make or model of automated liquid handler – the robotic instruments relied upon to increase productivity and reliability in the drug development, DNA testing, and clinical diagnostics arenas.

Supplanting the traditional methods of assessing automated liquid handler performance using gravimetry, flourometry, or single dye absorbance, the MVS is based on an innovation known as “ratiometric photometry”.  However, coming up with a modus operandi for validating the new system at the customer site was not as simple a development as the Artel team initially assumed.

Transferring Standards

Performance validation of new instrumentation at the customer site is commonly known as  IQ/OQ “installation qualification / operational qualification”.  This procedure generates data that can be traced back to reference standards external to any used by the instrument, and  allows operators to be confident in the data the instrument generates.   A key part of the IQ/OQ procedure for the MVS involves transferring minute amounts of liquid with great precision and accuracy.  Due to the global spread of Artel’s customer  base, the company needed a “transfer standard” that could be transported anywhere around the world.

Furthermore, such a transfer standard must accurately and precisely deliver the same volume of liquid independently of local environmental conditions such as heat, humidity and pressure, and also must  be as insensitive as possible to the peculiarities in operator technique that can dramatically affect the volumes delivered.  (It is well known that volumes delivered by traditional pipettes and syringes are affected by operator technique.)

The device also needed to perform at least as well as the other components of the system being validated.  In the case of the MVS, all the components of the system, including the transfer standard, must combine to have an accuracy of 98% or more, and a coefficient of variation of less than 0.4%

Initially, Artel’s service team discovered that positive displacement glass and steel syringes were less  affected by the temperature and pressure fluctuations that can lead to inaccuracy when using standard disposable pipettes.  But as anyone who has ever used a traditional syringe knows, reading the volume markings accurately can be a challenge.  This problem is exacerbated if you are in the middle of an installation and trying to answer questions about the instrument at the same time.

This led to the team fitting repeating adaptors to the syringes – which provide a mechanical stop and define the stroke length such that the user error is minimized.  However, the need to invert a vial and pierce a septum with the syringe (to avoid air ingress) led to needle blockages and the creation of a process that was laborious and, due to its unpredictable nature, oftentimes needed repeating.

Artel’s installation and service scientists became increasingly frustrated with this tedious process, as they found they were not able to spend as much time helping the customers become familiar with the MVS as they would have liked.  It also prevented them from assisting their clients with the liquid handling quality assurance challenges they faced.

The adaptors that were fitted to the syringes also caused challenges back at Artel headquarters in Portland, Maine – as the adaptor fitting screws had a propensity to work loose over time leading to a need for frequent recalibration and performance verification of the syringe itself, in order to ensure 100% performance at the customer site.  Since there was a need to qualify the instrument at a number of different volumes, as many as 12 different syringes had to be taken to an installation – each of which had to be kept well within its calibration specifications.

“Ensuring the glass syringes were always within calibration became a real nightmare for the Quality Control team at Artel,” said Vaccaro. “If syringes are handled with kid gloves in the laboratory then there aren’t too many problems, but no matter how carefully they are packed, the vibrations and knocks they are exposed to during transportation can send them out of calibration – and if that happens it is impossible for us to know whether the syringe fell out of calibration on its way to, or on its way back from an installation.  And, if there was even the slightest doubt of a syringe’s performance, we would then repeat the installation validation.”

evolsplasheVolving the process

During the LabAutomation conference in Palm Springs, CA, Vaccaro discovered an innovation that would dramatically improve the entire IQ/OQ workflow.  While assisting with the Artel Pipetting Challenge, an in-booth competition held at the conference that awards precision in an operator’s pipetting technique, Vaccaro encountered Glenn Clivaz, Director of SGE Analytical Science’s Liquid Handling Business Unit.  Clivaz was impressed by Artel’s use of their PCS® Pipette Calibration System to test the contestants’ technique, and wanted to use it in promoting the launch of the world’s first digitally-controlled analytical syringe – SGE’s award winning eVol®.

The eVol is a marriage of two precision devices:  A digitally controlled and programmable electronic drive and an XCHANGE® enabled analytical syringe.

“Seeing the eVol in action for the first time was a mind-blowing experience.  Not only was it easy to use, but the accuracy the users were getting with it were phenomenal,” said Vaccaro.  “All of the SGE personnel at the show were easily able to get gold medals in our Pipetting Challenge competition using the eVol – something I have never seen before.”

The eVol was designed to reduce the variability of volumes dispensed when different operators attempt the same volume transfer.  What’s more, unlike many pipettes, it is also suitable for transferring non-aqueous, viscous and hazardous liquids.  The eVol can be fitted with a number of different XCHANGE-enabled syringes allowing it to dispense volumes from 1mL down to 200nL.

George Rodrigues PhD, Artel’s Senior Scientific Manager, says the performance of the eVol is excellent, with the relative inaccuracy of the device at the full-scale values of 1 mL, 500 µL, 50 µL and 5 µL consistently measuring within 0.1%.  However, Rodrigues was most impressed with the accuracy and precision with which the 5 µL eVol could dispense 0.2 µL (200nL):  The eVol attained a relative inaccuracy of  0.41% and a coefficient of variation (%CV) of just 0.71%.

Because the eVol removes much of the human variability associated with using a positive displacement glass syringe fitted with repeating adaptors, the accuracy and precision of volumes dispensed has been much more easily ensured.

Due to the robust design  of the digital drive in the eVol, the device does not have the same propensity to wander out of calibration as a glass syringe, and this has halved the number of calibration cycles needed compared with glass syringes.  In addition, because the eVol’s performance can be validated at different volumes installation teams only need to take 3 XCHANGE- enabled syringes and an eVol body with them to an MVS installation, rather than 12 different syringes.

A Standard for Now and into the Future…

The increased user-friendliness of the eVol has led to dramatic time savings during installations, says Keith Albert PhD, Product Manager  for the Liquid Handler Performance Verification service at Artel, who is also frequently called upon to perform product installations and IQ/OQ testing.

“The eVol has definitely streamlined the instrument qualification process and lets us spend more time focusing on the customer – not the MVS instrument,” said Albert.  “Depending on the install or the type of service we are providing, we can save as much as an hour by using the eVol, and that allows us to provide our customers with better value for money – whether that is in the form of more hands-on training or more assistance with issues in the laboratory.”

According to Technical Services Manager Vaccaro, this has strengthened the relationship between customers and her field service team, as they are able to spend more time getting to know the customers and understanding the challenges they face with their automated liquid handlers and quality systems.

The nurturing of these increasingly meaningful relationships has maintained the high spirits within her team, and has led to the introduction of a number of product and service introductions to optimize the customer experience.  It has also contributed to the most important metric – positive customer feedback – becoming an almost daily occurrence.