SLAS

Error handling/Procedure evaluation and modificaton examples

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Error avoidance and handling in an automated laboratory system is largely a design issue, not a debugging issue.  Action should be taken during the design phase of a project to identify and if possible eliminate potential points of system errors.  Before any system design has been determined, the candidate procedure for automation must be screened for LUO executions that are potentially problematic for automated devices, with the option to: 

  • Leave these problem LUO's as manual operations within a largely automated procedure
  • Modify the problem LUO's to eliminate or minimize the potental for errors in the automated systems
  • Determine what error checking and recovery mechanisms can be built into the system to guard against errors that may be caused by the problem LUO's.


Following are real-life examples of this process:  

Solid dispensing[1]

  • A proposed automated procedure requires the dispensing of 10mg +/- 1mg of a solid from a bulk sample.  The following questions should be asked:
    • Is the weighing step important to be included within the fully automated process, or could it be performed manually?
    • Why 10mg +/- 1mg?  Is this an arbitrary number?  Can the process be scaled up?  Can less precision be tolerated? 
    • Is there automation technology that is capable of performing this task under the best of experimental circumstances?
    • Do the physical characteristics of the solid increase or decrease the odds of success? 

In this case, the weighing step was at the very beginning of a long process.  The physical characteristics of the solid were problematic for weighing - a sticky, hygroscopic compound.  Scaling up would not impact this.  Automated solid dispensing technology was unlikely to be reliable at that weight range given the physical characteristics.  It was decided to continue weighing the sample manually and begin the automated process from that step forward. 

Separation of solids and liquid in suspension[2]

  • A proposed automated procedure requires centrifuging a 20mL tube of cell suspension, decanting the supernatent, vortex resuspeding the solid cell mass pellet in wash solution, and stirring the resuspended solution with magnetic stir bar/stir plate.  The pellet often does not pack well and slides out of the tube along with the supernatent.  In such cases, lab technicians will return the supernatent and pellet to the tube and centrifuge for a longer period before again attempting to decant.  Sometimes the pellet packs too well and does not resuspend when vortexed.  In such cases, lab technicians will use a stirring rod to break up the pellet and then vortex.   
    • Is this process important to be included within the fully automated process, or could it be performed manually?
    • Is centrifuging the only option.  For instance, could the sample be filtered?
    • If centrifuging, is could aspiration be substituted for decantation?  Is the pellet height repeatable?  Would the remaining small amount of supernatent affect the subsequent reaction?
    • If all samples are centrifuged at a higher speed or spun longer, do any pellets slide out during decantation? 
    • What options exist for breaking up pellets that will not resuspend in a vortexer? 

In this case, these steps occurred in the middle of the process, and so needed to be included in the total automated procedure.  Filtration could not replace centrifugation.  The cell mass pellet size was quite variable, so aspiration was not suitable to replace decantation.  Centrifuge speed was already maxed out, but longer spinning did indeed stabilize all pellets across a multi-week test.  The resulting automated procedure was to centrifuge the cell suspension for an extended period, adding the magnetic stir bar prior to centrifugation, causing the stir bar to become imbedded in the centrifuged cell mass pellet.  The stir bar provided a heavy mass which would break loose and cause breakup and resuspension of the pellet when vortexed.   

References

  1. Hamilton, S.D. Avoiding and Handling Errors During Unattended Operation of Automated Laboratory Equipment, Laboratory Robotics and Automation, VCH Publishers Inc., 1989, 1, 53-61
  2. Hamilton,S.D. An Integrated Robotic Sample Preparation and HPLC Analysis of Biosynthetic Human Insulin, Advances in Laboratory Automation Robotics, J.R. Strimatis and G.L. Hawk editors, Zymark Corp., Hopkinton MA 1986 195