Jason Fawcett, Monique Mason, and Laura Pajak, Ph.D.
Beckman Coulter, Inc.
| Problem |
Possible Cause |
Solution |
| Low or no yield: |
- Poor cell lysis: Over grown bacterial culture resulting
in incomplete resuspension of bacterial cell pellet or clogging
of Lysate Clearing plate.
|
- Limit cell density (as measured at A600) of 1.0 to 4.0
OD600 per well.
|
- Overgrowth of bacterial culture by nontransformed cells
or bacterial culture is too old.
|
- Inoculate antibiotic-containing media with single
bacterial colony from a fresh plate. Make sure antibiotic
is present in the media.
|
- No ethanol or not enough ethanol added to wash
solution.
|
- Prepare the wash solution according to the instructions
provided along with the kit.
|
- Inaccurate quantitation of plasmid DNA yield.
|
- Run the sample on an agarose gel along with
known quantity of DNA ladder, stain the gel with ethidium
bromide and quantitate by comparing the intensities.
|
- Incomplete cell lysis due to poor resuspension
of bacterial pellet.
|
- Thoroughly resuspend cell pellet. Recommended
centrifuge speed is 1,500 x g. Excessive
centrifugation will result in poor resuspension.
|
- Poor resuspension of bacterial pellets.
|
- Use the full resuspension cycle included in
the Wizard. Adjust the volume of the resuspension solution
to the default value (250µl) or greater for large bacterial
pellets.
|
- Over growth of bacterial cultures, particularly
with strains containing Endonuclease I (EndA+) such as MC1061,
JM101, BL21.
|
- Grow cultures for a shorter time period, especially
when using TB broth (16 hrs). LB media 16-24 hrs. Saturation
conditions may cause cell lysis during culture resulting
in loss and degradation of plasmid DNA.
|
|
|
- Adjust vacuum pressure to 15” Hg with the vacuum
valve closed; reopen the valve before processing bacterial
plates.
|
- Vacuum valve not working or configured properly.
|
- Check that the vacuum valve has been set to
the correct com port and you can hear a ‘clicking’ noise
as the valve opens and closes.
|
|
| Filter plates not releasing from manifold
gaskets |
|
|
- Replace gaskets on manifold collar and spacer.
|
- Vacuum pressure too high.
|
- Adjust vacuum pressure to 15” Hg; alternatively,
increase the time in the “pause” steps after the vacuum
steps in the method to provide more time to allow for the
system to equilibrate to atmospheric pressure.
|
- The Labware Jog move is missing in the method
steps.
|
- Make sure that any method modifications did
not remove the jog step. Re-run the Wizard to restore the
original method.
|
|
| Genomic DNA contamination |
- Too many mix cycles at resuspension step.
|
- Reduce number of mix cycles at resuspension step.
|
|
| Poor or no restriction digestion |
|
|
- Prevent ethanol contamination by allowing full 10 min
of drying and blotting of the filter plate.
|
- Too much DNA used in restriction digestion mix.
|
- Quantitate DNA accurately by agarose gel/ethidium
bromide electrophoresis.
|
- Concentration of restriction enzyme and length
of digestion is not optimal.
|
- Check the manufacture’s suggestions for restriction
enzymes including recommended restriction buffer, concentrations,
and suggested temperature. This is particularly important
when using multiple enzymes in a single digest reaction.
|
|
| A ratio of A260/A280
that is less than 1.7 |
|
|
- Overgrown cultures may result in carryover of protein
by overloading the SV 96 system. Repurify plasmid DNA.
|
- Spectrophotometric reading performed using water (<pH
6).
|
- Perform spec reading in neutral water or TE
(pH 7.0- 8.0). Some purified waters are acidic and cause
an increase in the A 280 reading, making it appear like
protein contamination.
|
- Samples are contaminated.
|
- Make sure that the water source has enough volume
to accommodate the entire run. Otherwise the tips will not
be washed properly which may result in sample contamination.
It may be easier to have a continuous supply by connecting
a line directly to a water source to ensure an adequate
supply.
|
|
| Poor or no results with automated fluorescent
DNA sequencing |
|
|
- Make sure there is no ethanol contamination by allowing
the full 10 min drying and affixing fresh blot paper for
the blotting step.
|
- Too much or too little DNA used in sequencing reaction.
|
- Quantitate DNA accurately by agarose gel/ethidium
bromide electrophoresis in addition to spectrophotometric
analysis.
|
- TE buffer used for plasmid DNA elution.
|
- Elute plasmid DNA only in nuclease free water
provided in the kit.
|
|
| Reagents are not delivered appropriately |
- Incorrect positioning of reagents when running method.
|
- Consult the instrument setup screen to ensure reagents
are placed in the appropriate location.
|
- Circulating reservoir pump not turned on.
|
- The circulating reservoir pump is independently
controlled and does not automatically turn on. Before starting
a run make sure that the pump is on and that the liquid
in the reservoirs has had enough time to reach their operating
volume.
|
|
| Crashes occur when moving labware with
Gripper |
- Gripper fingers are worn, torn, or bent.
|
- Replace worn or torn finger pads, and bent fingers as
needed.
|
- The gripper or worksurface is inaccurately framed.
|
- Reframe the deck as necessary. Check framing
by moving a piece of labware on the deck before running
the method.
|
- Labware placed in the wrong position.
|
- Check instrument set up and make sure all labware
is in correct location.
|
- Improper labware definition.
|
- Review definition in the Labware Editor and
update if required. The labware can be reimported using
the Import file.
|
|
| Cannot move collar from the SPE ALP
to the Holder |
- Gripper inaccurately framed.
|
- Reframe gripper and/or adjust the squeeze/unsqueeze values
for the collar and collar spacer in the labware editor.
|
|
| Vacuum bottle collapsing |
- Source vacuum is too high.
|
- Check that the dead end vacuum pressure is 15”Hg.
|
- Inappropriate bottle material.
|
- Check base of bottle for “PP” (Polypropylene)
designation. Replace with bottle made of correct material.
|
|
| Method Errors |
- Stacker Carousels cannot be detected.
|
- Make sure that the stacker carousels are connected to
the correct com port and are configured properly in the
hardware setup utility.
|
- Stacker Carousels have not been configured properly for
the correct hotel types.
|
- Select the appropriate hotel stack in the hardware
setup. For this method all the stacker carousel hotels are
stack 10’s.
|
- There is no device associated with the SC1 and
SC2 deck positions.
|
- In the deck editor make sure that the SC1 and
SC2 positions have a stacker device associated with that
position. For position SC1 the device should be Stacker1
and for position SC2 the device should be Stacker2.
|
- The software cannot detect the FX.
|
- Make sure the Biomek FX is connected to the
correct com port on the computer and then select that com
port in the hardware setup.
|
- No device controller installed.
|
- The wash pumps will not work if the device controller
is not installed properly. Check that there is a device
controller installed in the hardware setup utility and the
corresponding wash pumps are also installed.
|
- No device associated with wash stations.
|
- In the deck editor make sure that each wash
position has a wash pump associated with the position.
|
- Wash pump on wrong line on the device controller.
|
- Connect the wash pumps to the appropriate line
on the device controller and maker sure the wash pumps are
correctly configured in the hardware setup utility.
|
- Beckman pump installed in simulation when the
Wizard was installed.
|
- Reinstall the Wizard and select install pump
with real hardware.
|
- The additional roving height is too high.
|
- Adjust the additional roving height in the pod
editor to 0.55cm. This will allow enough space for the Biomek
to move things around the deck without giving a Z-max error.
|
- The min safe height for the stacker carousels is too high.
|
- In the deck editor adjust the min safe height for the
stacker carousels until the error is removed. Typically,
decreasing the min safe height will clear the error.
|
- Attempting to frame the holder position on the 2x1 ALP.
|
- The 2x1 ALP only needs the SPE position framed. The holder
position does not need framing.
|
- Beckman pumps not installed on correct com ports.
|
- Under the device setup menu make sure that each Beckman
pump is connected to the correct com port.
|
- Stacker carousels cannot initialize because they have
labware blocking the sensors.
|
- Remove the top pieces of labware from Hotels A and C.
Turn the stacker carousel on and off. Once they have re-initialized
replace the removed labware.
|
|
* All trademarks are the property of their respective owners. Where applicable,
the PCR process is covered by patents owned by Roche Molecular Systems,
Inc., and F. Hoffman-LaRoche, Ltd.