This protocol describes how to create and execute a worklist to analyze a batch of samples using ChEM-H's 6545 Q-TOF mass spectrometer. The protocol guides users through the steps of preparation, instrument power-on, calibration, column preparation, and starting an analysis run. This protocol assumes default choices for chromatography column and ion source.
Safety glasses and nitrile gloves are required for this protocol.
Your samples must be prepared for LC-MS analysis.
- All samples must be filtered using 0.45 μm or 0.22 μm filters. Avoid freezing your samples after filtering.
- Your samples must be in either HPLC vials or 96-well plates. The containers for your samples must be compatible with organic solvents such as methanol or acetonitrile. This most commonly means that glass vials or polypropylene plastics must be used. Avoid polystyrene and similar materials.
- The minimum volume of each sample depends on the container type.
This protocol assumes users will be using our standard reversed-phase chromatography setup. Our default choice is a 50 mm × 2.1 mm Zorbax RRHD Eclipse C18 column with 1.8 μm beads (Agilent #959757-902). The column should be fresh or recently cleaned. See protocols (forthcoming) on cleanup of reverse-phase chromatography columns for more information.
Ensure the instrument has the proper ion source for your application attached. This will usually be the Agilent dual AJS electrospray ion source.
- Reference bottle A
- Tuning Mix bottle B Both of these bottles housed in the LC-MS itself should be full. See this document for information on the composition of the tuning mix.
- HPLC gradient system diagnostics mix (Aldrich #48271). This should usually be present in the
Vial 1
position inside the autosampler.
- Line A1: HPLC-grade water containing 0.1% v/v formic acid, e.g. .
- Line B1: HPLC-grade acetonitrile containing 0.1% v/v formic acid.
- Needle wash / pump head wash: 15% v/v HPLC-grade isopropanol in HPLC grade water
Each bottle should contain more than 300 mLs of buffer.
Prepare a worklist for your samples using Microsoft Excel or Google Sheets or a similar program. The spreadsheet you use should contain the following columns:
Sample Name | Sample Position | Method | Data File | Inj Vol (μL) |
---|---|---|---|---|
my_fav_samp | P1-A1 | my_meth.m | my_fav.d | 1 |
002 | P1-A2 | my_meth.m | 002.d | 1 |
condition_B_again | P1-A3 | my_meth.m | B_again.d | 1 |
... | ... | ... | ... | ... |
We recommend that the first injection -- and approximately every 20th injection you make -- be of HPLC gradient system diagnostics mix (Aldrich #48271).
We also recommend that you randomize injection order for your samples.
- Ensure you have reserved time on the GNPN ChEM-H LC-MS Schedule, a Google Calendar used to reserve time on the instrument.
- Ensure the instrument is prepared for your run.
- Ensure that all required equipment, including (filtered) samples, the appropriate chromatography column, the proper ion source, calibrants, and chromatography buffers and needle washes, are present.
- Ensure that waste containers are not full.
- Ensure that nitrogen sources to the instrument are adequately pressurized.
- Ensure the instrument state is as you desire. This should usually be
Low (1700) 2 GHz, Ext Dyn Range
orEDR 1700
.
- Put your samples in the autosampler. If needed, move old samples from previous users to the "Old Samples -- Will Be Discarded Soon" shelf.
- Open MassHunter Workstation Data Acquisition software if it is not already open.
- Begin filling out the required log sheet. Enter your SUNET ID, sample types, column type and location. Check off the box for completing instrument inspection.
- Open your analysis method. It should use a chromatographic flow rate of 0.6 mL / min.
- Let the ion source, column oven, and other components warm up. Wait until the indicator for each component turns GREEN.
- Calibrate the instrument.
- Switch from
Acquisition
toTune
context.- You do not need to save changes to your Layout, and probably do not need to save changes to the instrument Method.
- Check off the appropriate calibrations. If you are running samples in both positive and negative polarities, you should calibrate the instrument in both polarities. If you are performing MS2 experiments, you should calibrate the quadrupole as well as the TOF.
- Click the
B
radio button to open bottle B and let calibrant flow into the MS. Observe the calibrant peaks form. - Click the
Start TOF Mass Calibration
. Ignore all references to the "dual AJS splitter valve."- The button text will be slightly different if you are calibrating the quadrupole instead of or in addition to the TOF.
- Record the maximum raw deviation that obtained from the calibration on the log sheet.
- Return to the
Acquisition
context. ClickYES
when asked if you want save the modifications to your tune file.
- Switch from
- Set up your Worklist.
- Set the default file paths for methods and data in
Worklist Run Parameters
. - Show/hide the columns in the Worklist view to match the columns in the sample Worklist shown above.
- Copy and paste from Excel to Acquisition.
- Add the
InstrumentStandby
script to the end of your worklist. Check off the space on the log sheet to indicate that you have done so.- This prevents endless pumping of chromatography buffer, dried pumpheads, overflowing waste containers, etc.
- Save your worklist.
- Set the default file paths for methods and data in
- Ensure the autosampler plate types are set correctly. Right click on the autosampler module, select "Assign Wellplates". Make sure the plate types defined in the software match the plate types in the autosampler.
- Check the details of your data acquisition methods one last time.
- Are you diverting the first few column volumes to waste? This is a good idea if you have "dirty" samples.
- Are you recording UV spectra? At the right wavelengths?
- Are your MS and MS/MS acquisition parameters set correctly?
- Click the "Start Worklist Run" button.
- Watch the first sample inject to be sure no errors occur.
- Observe the UV absorption data in the Acquisition window to make sure the peaks in the first injection (of the external standard) look correct.
- You are free to leave and let the instrument do its work. It's a good idea to check in on your run periodically using AnyDesk.
- If you want your samples back, retrieve them from the autosampler before your reserved time on the calendar ends.
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