Small Molecule Mass Spectrometry
The Center for System Biology Small Molecule Mass Spectrometry laboratory strives to increase the quality and availability of mass spectrometric instrumentation in the areas of accurate mass determination, confirmation and structure elucidation of organic compounds and biological samples with a wide range of mass spectrometric techniques.
Services
Two types of services are available: Open Access and Fee For Service. Open Access offers trained users a walk-up service where users can choose from various pre-programmed experimental methods and obtain results 24 hours, 7 days a week. Fee For Service allows users to submit samples with a submission form containing sample information to our facility and results are emailed to users once they are obtained. Below, please find the type of ionization methods and instruments we have in our facility for these services.
Open Access- Low resolution direct flow injection ESI MS and ESI LC/MS
- High resolution direct flow injection ESI MS
- Low resolution direct flow injection APCI MS and APCI LC/MS (available soon)
- Low resolution direct flow injection APCI/ESI MS and APCI/ESI LC/MS (available soon)
- Low resolution GC/MS
- Low resolution GC/MS/MS
- Low resolution MALDI TOF
- Low resolution direct flow injection ESI MS and ESI LC/MS
- High resoltuion direct flow injection ESI MS
- Low resolution direct flow injection APCI MS and APCI LC/MS
- Low resolution GC/MS
- Low resolution CI/EI/FAB MS
- High resolution CI/EI/FAB MS
- Low resolution MALDI TOF
*(please note the turnaround time are as follows: low resolution (~2-5 business days), high resolution (~5-10 business days). In most cases, the turnaround time is much shorter. Rush service is also available. Please call our facility for more details.
Data Analysis
Data Analysis is an essential part of mass spectrometry. Our facility provides data analysis and interpretation consultation service.
Each of the open access instrument is set up to aquire and process data automatically. In most cases, a data report is printed when acquisition has completed. Agilent LC instruments (time of flight and quadrupole) will send a data report via email and the data report can be opened using DataBrowser which can be loaded on your personal computer (Windows platform only). DataBrowser can be obtained from our facility and it will be available soon on the FAS software page.
Fee For Service results are generally delivered in pdf format wherever possible. Please feel free to contact us, before and after sample submission, and we will ensure your sample is carried out correctly. We encurage you to discuss your experimental results with us.
Forms
Two types of fee for service forms are available:
- If you have a Harvard 33 digit billing code, please download this form: Internal User
- If you do not have a Harvard 33 digit billing code, please download this form: External User
Please consult our staff if you would like to submit for GC/MS or MALDI analysis.
Rates
Open Access
| Harvard | Non-Harvard | |
| Low Resolution OA FIA | $25 | n/a |
| High Resolution OA FIA | $25 | n/a |
| Low Resolution OA ESI LC/MS | $25 | n/a |
| Low Resolution OA GC/MS | $25 | n/a |
| Low Resolution OA GC/MS/MS | $15 | n/a |
| Low Resolution OA MALDI | $45/hr | n/a |
Fee For Service
Harvard | Non-Harvard | |
| Low Resolution CI, EI or FAB | $35 | $70 |
| High Resolution CI, EI or FAB | $80 | $115 |
| Low Resolution APCI, ESI | $35 | $70 |
| High Resolution ESI | $75 | $115 |
| Low Resolution APCI or ESI LC/MS | $60 | $115 |
| Low Resolution GC/MS | $50 | $90 |
| Low Resolution MALDI | $95 | $115 |
Fees are per experiment unless otherwise noted.
Sample Preparation
Sample preapration is crucial in obtaining good results in mass spectrometry. There are several general factors namely, purity, concentration, salt content, solvent used and the nature of compound. Below, please find the guidelines to different services.
Please feel free to consult with us and we would gladly recommend the best sample preparation depending on your needs. Our contact information can be found on the Contact page.
Fee For Service
sample preparation
General Information
Six instruments are able to accept submission:
- Agilent 6120 Quadruple LC/MS with ApCI/ESI source and fraction collector
- Agilent 6210 Time-of-Flight LC/MS
- Agilent 6890 GC/MS
- JEOL SX102 magnetic sector with EI/CI/FAB methods
- Micromass LCT
- Applied Biosystems Voyager RP MALDI
Each sample MUST be submitted with a submission sheet with all fields filled out. Unless otherwise requested, all samples will be carried out by ESI before other ionization techniques will be performed. Users wishing to submit for MALDI analysis should consult the laboratory personnel before submitting samples. If you have a sensitive compound (air/moisture etc), please consult the laboratory staff to schedule an appointment
Submission Sheets
To assist our personnel optimizing experimental conditions, proposed compound structure should be provided. An internal and an external form are available. For those have a Harvard 33 digit billing code, please use the internal form. All others should use the external form. Forms can be found here: Forms
Submission Process- There is one "In" tray, located on top of the mailboxes against the wall as you enter the facility.
- Sample vials may be taped to the sheets (if stable in room temp.) or placed in the tray on the top shelf in the fridge next to the mailboxes.
- All samples MUST be labeled.
- Samples should be submitted and fully-dissolved (in suitable solvents) in chromatography auto-injector vials (available in the stockroom) at an appropriate concentration (~0.1 mg/mL).
- Partial solubility is not acceptable.
- Solid sample placed in vials may be submitted ONLY if the sample is not stable in liquid solvents and please identify a solvent that will dissolve your sample completely on the submission sheet.
Open Access
SAMPLE PREPARATION
General Information
These instruments are setup for open access:
- Agilent 1100 HPLC with fraction collector (here or new page?)
- Agilent 6120 Quadruple LC/MS with ApCI/ESI and fraction collection (coming soon)
- Agilent 6210 Time-of-Flight LC/MS
- Agilent 6890 GC/MS
- Applied Biosystems Vision Preparative Scale HPLC (here or new page?)
- Applied Biosystems Voyager DE-Pro MALDI-TOF
- Waters Quattro micro GC/MS/MS
Open Access (OA) provides a "Do It Yourself" mechanism for users to acquire mass spectra. Sample information is entered into a "Login Interface" by the user. Samples are prepared in auto injector vials and placed in the instrument's auto injector rack as instructed by the login system. Data are printed out after each sample has been analyzed. You can also log in a batch of samples. Samples need to be compatible with the instrumental solvent system and ionization technique to achieve the best results.
Submission Sheet
No submission sheet required. All user information is pre-entered and login is created.
Submission Process
Samples are prepared in solution in an auto-sampler vial. Vials must be compatible with Agilent HPLC or GC auto-samplers. Samples are dissolved in an appropriate solvent (see FAQ for compatibility issues). Obtaining a reasonable sample concentration is crucial. No more than a few ppm (parts per millions) should enter the instrument. This is because too much sample will cause a number of problems.
| Method | Mode | Concentration (mg/mL) | Concentration (ppm) |
| FIA | Positive | 0.001 | 1 |
| FIA | Negative | 0.01 | 10 |
| LC/MS | Positive | 0.01 | 10 |
| LC/MS | Negative | 0.05 | 50 |
| GC/MS | Positive | 0.05 | 50 |
Instruments
OPEN ACCESS INSTRUMENTS
Agilent 6120 Quadrupole LC/MS with Multimode source A single quadrupole instrument capable of unit mass resolution to 1500 amu. The instrument is equipped with a Multimode source capable of simultaneous APCI and ESI ionization in both positive and negative ion modes. Samples that ionize in solution are generally analyzed in ESI-only mode; those that do not are generally analyzed in APCI-only mode. Samples with poorly defined or unknown characteristics can be analyzed in Multimode combining ESI and APCI in a single run. The instrument is configured for either flow injection or HPLC introduction of samples from an automatic sampler. Samples with unique sensitivities (organometallics or air-sensitive samples, for example) can be introduced from a syringe prepared under conditions controlled by the user. The mass spectrometer is equipped with a fraction collection system allowing peak collection based on a specific mass, total ion current, UV absorbance, or a combination the three. Preparative chromatography can be accommodated at flow rates up to 5 mL/min.
Agilent 6210 Time-of-Flight LC/MS A time-of-flight instrument that is capable of unit mass resolution to 13,000 amu. This instrument is equipped with a high pressure LC binary bump and a dual nebulizer ESI source. The spectral acquisition rate can be as high as 40 spectra per second. As reported by Agilent, the mass accuracy is less than 2 ppm with an internal mass reference solution. This instrument is capable of producing both low and high resolution (to 4 decimal places) mass determinations as well as LC/MS separations with dioarray UV traces. Softwares MassHunter and EasyAccess are setup for users to walk up and login samples with few basic information entries.
Hewlett Packard (Agilent) HP6890GC/5973MSD GC/MS equipped with HP-1 30m x 0.25µm capillary column operating in the splitless mode that works for small, volatile and semi-volatile molecules. The ionization technique is electron impact (EI) and carrier gas is Helium. The acquisition software is ChemStation and an open access software is setup to allow users to choose a set of methods ranging from low to high molecular masses (50 to 800) and at different ramping rates. NIST library is also available for references.
Applied BioSystems DE Pro MALDI A linear MALDI TOF instrument with delay extraction capable of unit mass resolution to at least 1200 AMU, and lower resolution beyond that. In principle there is no upper mass limit. MALDI is generally used to characterize nonvolatile compounds (peptides and proteins, for example) and produces mainly singly charged ions in both positive and negative modes. MALDI TOF is a “gentle” ionization technique, and can be used to produce intact molecular ions when other means of analysis result in fragmentation. Samples are prepared and spotted onto a sample plate off-line, then introduced into the instrument. Data collection for each sample is rapid, usually a matter of only a few minutes.
Waters Quattro micro GC/MS/MS A triple quadrupole mass spectrometer with an Agilent 6890 GC and CTC CombiPAL autosampler has a mass range from 4 to 1500 amu. Headspace sampling allows direct volatile compounds injections. The ionization techniques are electron impact (EI) with carrier gas Helium and Chemical Impact (CI) with methane. It can be used for many methods such as multiple reaction monitoring (MRM), pproduct ion, precursor ion and neutral loss/gain. Masslynx is the acquistition software and OAlogin is the open access software.
FEE FOR SERVICE INSTRUMENTS
Applied Biosystems Voyager RP MALDI A linear MALDI TOF instrument capable of unit mass resolution to at least 1200 AMU, and lower resolution beyond that. In principle there is no upper mass limit. MALDI is generally used to characterize nonvolatile compounds (peptides and proteins, for example) and produces mainly singly charged ions in both positive and negative modes. MALDI TOF is a “gentle” ionization technique, and can be used to produce intact molecular ions when other means of analysis result in fragmentation. Samples are prepared and spotted onto a sample plate off-line, then introduced into the instrument. Data collection for each sample is rapid, usually a matter of only a few minutes.
Micromass LCT An electrospray ionization (ESI) mass spectrometer equipped with a HP1100 LC system and a syringe pump. This instrument can be used to measure low and high resolution masses in both positive and negative modes. It is suitable for small to large organic molecules ranging from 100 m/z to 3000 m/z including peptides, proteins and DNA samples. LC/MS can also be carried out using this instrument. The acquisition software is MassLynx.
Waters Q-Tof micro LC/MS/MS The Waters Q-Tof micro LC/MS/MS system consists of a time-of-flight tandem mass spectrometer equipped with both a normal and a nano ESI sources, Waters 2695 HPLC, Eksigent nanoLC and Waters Masslynx software. The instrument features two systems, normal LC/MS/MS and nano LC/MS/MS. For normal LC/MS/MS system, it has full-scan LC/MS/MS performance, the automated exact mass measurement in both MS and MS/MS modes; For the nanoLC-ESI-MS/MS system, the flow rate is from 50 to 1000 nL per minute. The great selectivity gains are observed. The sample consumption is reduced up to a few fmol for 4-mer oligonucleotide in the negative mode. The instrument is configured for either flow injection or HPLC introduction of samples from an automatic sampler. The powerful data-collection and processing tools enhance the quality and timeliness of analytical results. The Q-Tof micro is used extensively in several application areas such as, metabolite profiling, proteomics, DNA, DNA adducts and food safely as well as general analytical studies.
ADDITIONAL LC SYSTEMS
Agilent 1100 HPLC An analytical scale HPLC with a fraction collector which can be used to separate and analyze components within a chemical mixture. The injection volume of the autosampler is 1-100 uL. The pump flow rate is 0.1-2 mL/min. Chemstation software is used for control and data analysis.
Applied Biosystems Vision preparative HPLC A LC system is used for separating and analyzing large scale of chemical mixture. The AFC injection system can inject as much as 1-5 mL samples and the typical flow rate during the run is 10-20 mL/min.
Training
Open Access trainings on the following instruments are held every week. Please contact our facility to schedule a session.
Open Access Training Handout:
Agilent 1100 HPLC with fraction collector (available soon)
Agilent 6120 Quadruple LC/MS (available soon)
Applied Biosystems Vision Preparative Scale HPLC (available soon)