Created: 1st March 2000, last updated: 30th May 2000, © 2000 ABRF
Debra A. McMillen,a Lisa Bibbs,b Nancy Denslow,c Kathryn M. Ivanetich,d Clayton Naeve,e Ronald L. Niece,f and Stephen Tindallg
aInstitute of Molecular Biology, University of Oregon, Eugene, OR; bThe Scripps Research Institute, La Jolla, CA; cProtein Chemistry and Molecular Biomarkers Lab, University of Florida, Gainesville, FL; dBiomolecular Resource Center, University of California, San Francisco, CA; eCenter for Biotechnology, St. Jude Children's Research Hospital, Memphis, TN; fUniversity of California, Irvine, CA (currently at Research Resources and Technologies, Tustin, CA); gArgo BioAnalytica, Inc., Morris Plains, NJ
An assessment of the capabilities of biotechnology core facilities requires access to current data on state-of-the-art technologies, personnel, space, services, financial issues, and the demand for such facilities. Data on these topics should be useful to researchers, facility personnel, administrators, and granting agencies. To obtain such data, the Association of Biomolecular Resource Facilities (ABRF) conducted a general survey on the operation and technical capabilities of core facilities. A total of 81 ABRF core laboratories voluntarily responded to the survey. Just over 60% of the respondents were from academic institutions, with the remaining located in research institutes, industry, and one U.S. government laboratory. Fifty laboratories provided financial data, with 47 of these operating on a nonprofit basis. Four laboratories were fully self-supporting from user fees. A typical facility had three full-time staff members and occupied approximately 1100 square feet (ft2). The most frequently offered services were N-terminal protein sequencing, protein fragmentation, peptide synthesis and purification, amino acid analysis, DNA synthesis, and DNA sequencing. One third of the facilities provided mass analysis by matrix-assisted laser desorption and ionization (MALDI) mass spectrometry, a recently introduced service that has been offered on an average for 3 years. Another relatively new service, bioinformatics support, is offered by about one third of the responding laboratories. (J Biomol Tech 2000;11:1-11)
Key Words: biotechnology, core facility, DNA, protein.
Address correspondence and reprint requests to: Debra A. McMillen, Institute of Molecular Biology, University of Oregon, Eugene, OR 97403 (email: mcmillen@molbio.uoregon.edu).
One aspect of the mission of the Association of Biomolecular Resource Facilities1 (ABRF) is to promote and support resource facilities and their interactions with research laboratories. A profile of biotechnology resource laboratories may be useful in the creation of new core facilities, as well as in the redefinition of the operation of established facilities. This report is the fourth in a series of surveys2-4 conducted by the Survey Committee of the ABRF to provide information on the changing face of biotechnology core facilities. Topics covered in this survey include details about personnel, space requirements, services offered, number of research laboratories served, sample throughput, charges, cost recovery, and funding issues. Current trends in core facilities have been identified by comparison with the results of the last general survey, which was conducted in 1992.4
FIGURE 1. Comparison of the percentage of reporting core facilities offering selected services in 1998, 1992, and 1987. Data are taken from results of this survey and earlier surveys.2,4
The six-page questionnaire for this survey was posted in January of 1998 on a website established by Lisa Bibbs and Jose Gutierrez of The Scripps Research Institute. Directors of ABRF core facilities were notified of the survey by United States mail and by email through the ABRF electronic discussion group (abrf@aecom.yu.edu). To provide anonymity for responses to the survey, respondents obtained a unique identifier code from Gutierrez. Laboratories wishing to respond electronically through the website submitted each of the six pages of the survey as they were completed. Respondents who preferred to submit a written response were provided with a paper copy of the survey. Eighty-one data sets were collected, with the last data set received in June of 1998.
Data entries that appeared to be inconsistent were clarified if possible by contacting the facility through Gutierrez. The sample size (N), mean, median, and standard deviation (SD) were calculated for each data set. The range includes all of the values reported by facilities with the exception of the outliers. Outliers were defined as data points that differed from the mean by more than four times the standard deviation and were removed from the data sets. In some cases, respondents did not answer all questions in the survey; this is reflected in the sample size. Data sets that had a sample size of less than or equal to 4 were not included in the tables or in the statistical analysis. Student's t test for unpaired data was used to determine the statistical significance of differences between means. A significant difference was taken to be P < 0.01, with P < 0.05 as a probably significant difference. A copy of the survey is available from the corresponding author. Preliminary results from this survey were presented as a poster at the ABRF '99 meeting entitled Bioinformatics and Biomolecular Technologies: Linking Genomes, Proteomes and Biochemistry, held March 19 through 22, 1999, in Durham, North Carolina.
A very different profile of services offered by a typical facility was seen in 1998, compared with the previous major surveys in 19872 and 19924 (Fig. 1). The most striking difference seen in Figure 1 is the decrease in the percentage of facilities offering each service, with the exceptions of capillary electrophoresis, DNA sequencing, and mass spectrometry. In 1998, the most commonly offered services (Table 1) were protein sequencing (62%), protein fragmentation (44%), peptide synthesis (42%), amino acid analysis (39%), synthetic peptide purification (38%), DNA sequencing (37%), and DNA synthesis (37%). In 1992, the distribution of facilities offering these services was as follows: protein sequencing (87%), protein fragmentation (31%), peptide synthesis (59%), amino acid analysis (76%), DNA sequencing (14%), and DNA synthesis (49%).
TABLE 1
Services Offered in 1998 and the Number of Years Offered
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| Years | ||||||||||
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| Service | N | Median | Mean | SD | Range | |||||
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| DNA services | ||||||||||
| DNA synthesis 1-4a | 29 | 11 | 10.5 | 2.8 | 4-14 | |||||
| DNA synthesis highb | 6 | 2 | 4.1 | 5.4 | 1-15 | |||||
| DNA oligo purification | 15 | 10 | 8.7 | 4.2 | 3-15 | |||||
| Template prep | 6 | 2 | 3.6 | 4.0 | 1-11 | |||||
| DNA sequencing | 29 | 6 | 5.7 | 2.9 | 1-10 | |||||
| Microsatellite analysis | 11 | 1 | 2.1 | 1.8 | 1-6 | |||||
| Protein services | ||||||||||
| N-terminal protein seq | 49 | 10 | 10.3 | 4.6 | 1-24 | |||||
| SDS-PAGE | 18 | 8.5 | 8.6 | 4.0 | 3-20 | |||||
| 2D gels | 10 | 1.5 | 2.9 | 3.1 | 1-10 | |||||
| Fragmentation | 35 | 7 | 7.3 | 4.9 | 1-20 | |||||
| Peptide synthesis 1-3c | 33 | 9 | 8.6 | 3.5 | 1-14 | |||||
| Peptide synthesis highd | 11 | 6 | 6.4 | 3.9 | 1-15 | |||||
| Peptide purification | 30 | 9 | 8.6 | 3.6 | 1-15 | |||||
| Amino acid analysis | 31 | 12 | 12.2 | 6.1 | 4-30 | |||||
| CEe | 12 | 5 | 4.6 | 2.2 | 1-8 | |||||
| HPLCf | 21 | 8 | 8.1 | 4.9 | 1-20 | |||||
| Mass spectrometryg | ||||||||||
| MALDI (mass) | 26 | 2.5 | 2.7 | 1.8 | 1-8 | |||||
| MALDI (sequence) | 5 | 2 | 1.8 | 0.8 | 1-3 | |||||
| Electrospray (mass) | 16 | 4 | 3.7 | 2.4 | 1-8 | |||||
| Electrospray triple quad | 11 | 4 | 4.0 | 2.4 | 1-8 | |||||
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aDNA synthesis 1-4: synthesis with a 1 to 4 column instrument.
bDNA synthesis high: synthesis with a >4 column instrument.
cPeptide synthesis 1-3: synthesis with an instrument with up to
three reaction vessels.
dPeptide synthesis high: synthesis with an instrument with more
than 3 reaction vessels.
eCapillary electrophoresis.
fHigh performance liquid chromatography.
gSubcategories of mass and sequence were defined for MALDI and
mass for electrospray with the second category not defined to
accommodate multiple uses.
The percentage of laboratories offering mass spectrometry has tripled since 1992, and the percentage offering DNA sequencing has more than doubled. Amino acid analysis, carbohydrate analysis, and high-performance liquid chromatography (HPLC) services have dropped by more than one half since 1992. The remaining services are currently offered by approximately the same percentage of laboratories as reported in the 1992 survey. New services that have been added since 1992 include high-throughput DNA synthesis, DNA template preparation, microsatellite analysis, C-terminal protein sequencing, two-dimensional (2D) gel electrophoresis, bioinformatics, and all categories of analysis by mass spectrometry.
The service that has been offered for the longest average period (12 years) was amino acid analysis. DNA synthesis with a 1- to 4-column instrument (Table 1, footnote a) and N-terminal protein sequencing were the next oldest services, with 10 years each. Services that have been offered for 5 to 9 years include DNA oligonucleotide purification, DNA sequencing, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), protein fragmentation, peptide synthesis, peptide purification, carbohydrate analysis, and HPLC.
Survey participants were asked to provide information regarding bioinformatics services offered by their laboratories. Bioinformatics, defined here in its broadest sense, can range from simple database searches to complex molecular modeling. Of the 81 responding facilities, 32% offered some form of bioinformatics services. Of these, 62% had dedicated bioinformatics support staff, and 88% had dedicated space, averaging 84 ft2. Only three of the 26 laboratories charged for this service, and only 10 facilities offered training in the use of bioinformatics resources.
Facilities were asked to report other services that they provide beyond those listed in the survey. HPLC protein purification was offered by two laboratories. Circular dichroism was also offered by two laboratories. Fermentation, fluorescence spectroscopy, optical biosensor studies, modeling, imaging, genechip microarray technology, and quantitation by real-time polymerase chain reaction (PCR) were each mentioned once as other services offered by the respondents demonstrating the breadth of technologies implemented in core facilities.
According to survey results, 10 (12%) of the responding facilities from industry, research institutes, and academic institutions performed some services under Good Lab Practices (GLP) guidelines. GLP standards for amino acid analysis were offered by four laboratories, and five did so for protein sequencing. Two offered GLP services for DNA synthesis, two for DNA sequencing, two for peptide synthesis and purification, and three for electrospray mass spectrometry. Carbohydrate analysis, capillary electrophoresis, 2D gel electrophoresis, and HPLC were all mentioned once as offered under GLP guidelines.
Among individual services, there was a wide range in sample throughput per month (Table 2). The data also show that there was a wide range in throughput reported by the responding laboratories for any one service. This can be seen in the large standard deviations and ranges that are reported. Automated DNA sequencing (1180 ± 1100 samples/month) had the highest throughput on average, followed by high-throughput DNA synthesis (700 ± 510) and microsatellite analysis (640 ± 1470). The lower throughput for synthetic DNA purification (74 ± 66) may reflect the fact that most synthetic oligonucleotides do not need purification.
TABLE 2
Number of Samples per Month
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| Service | N | Median | Mean | SD | Range | |||||
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| DNA services | ||||||||||
| DNA synthesis 1-4 | 28 | 200 | 244 | 244 | 20-1218 | |||||
| DNA synthesis high | 6 | 688 | 697 | 508 | 80-1327 | |||||
| DNA oligo purification | 14 | 45 | 74 | 66 | 3-180 | |||||
| Template prep | 5 | 100 | 215 | 329 | 5-800 | |||||
| DNA sequencing | 28 | 900 | 1176 | 1096 | 169-5000 | |||||
| Microsatellite analysis | 11 | 100 | 641 | 1466 | 10-5000 | |||||
| Protein services | ||||||||||
| N-terminal protein seq | 49 | 17 | 27 | 25 | 3-120 | |||||
| SDS-PAGE | 16 | 2 | 4 | 6 | 1-25 | |||||
| 2D gels | 8 | 6 | 8 | 8 | 1-20 | |||||
| Fragmentation | 34 | 4 | 13 | 19 | 0.1-91 | |||||
| Peptide synthesis 1-3 | 35 | 9 | 10 | 8 | 0.5-35 | |||||
| Peptide synthesis high | 11 | 15 | 19 | 13 | 5-40 | |||||
| Peptide purification | 31 | 5 | 8 | 9 | 0.3-35 | |||||
| Amino acid analysis | 28 | 24 | 63 | 80 | 0.3-300 | |||||
| Mass spectrometry | ||||||||||
| MALDI (mass) | 25 | 50 | 163 | 254 | 5-1000 | |||||
| MALDI (sequence) | 5 | 1 | 12 | 22 | 0.5-50 | |||||
| Electrospray (mass) | 16 | 45 | 322 | 983 | 10-4000 | |||||
| Electrospray triple quad | 12 | 18 | 44 | 58 | 0.5-200 | |||||
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The number of instruments per service ranged from one to eight, with most laboratories reporting one or two instruments per service. On average, the services (which typically had two instruments) included low-throughput DNA synthesis, DNA sequencing, protein sequencing, SDS-PAGE, 2D gels, protein fragmentation, and synthetic peptide purification. The remaining services had an average of one instrument.
With regard to the number of cycles per month (eg, the number of base additions in DNA synthesis), high-throughput DNA synthesis had the highest average at 19,000 cycles per month, followed by low-throughput DNA synthesis (5200 cycles). N-terminal protein sequencing and peptide synthesis ranged from 150 to 400 cycles.
The services with the fastest delivery (Table 3) or turnaround time (<3 days) were DNA-related services, including high- and low-throughput DNA synthesis, synthetic DNA purification, DNA sequencing, and template preparation. Somewhat longer turnaround times of 4 to 6 days were reported for microsatellite analysis, N-terminal protein sequencing, amino acid analysis, and SDS-PAGE. The longest turnaround times, ranging from 8 to 14 days, were for protein services, including protein fragmentation, 2D gels, and peptide synthesis (high and low throughput), and peptide purification.
TABLE 3
Turnaround Time
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| Days | ||||||||||
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| Service | N | Median | Mean | SD | Range | |||||
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| DNA services | ||||||||||
| DNA synthesis 1-4 | 28 | 2 | 2.1 | 0.8 | 1-4 | |||||
| DNA synthesis high | 6 | 1.5 | 1.6 | 0.4 | 1-2 | |||||
| DNA oligo purification | 14 | 2 | 2.5 | 1.9 | 0.5-7 | |||||
| Template prep | 6 | 2 | 2.8 | 1.7 | 1-5 | |||||
| DNA sequencing | 30 | 2 | 2.8 | 1.4 | 1-7 | |||||
| Microsatellite analysis | 11 | 2 | 3.8 | 3.9 | 1-14 | |||||
| Protein services | ||||||||||
| N-terminal protein seq | 49 | 4 | 5.1 | 4.3 | 1-21 | |||||
| SDS-PAGE | 16 | 3.5 | 4.3 | 3.5 | 1-15 | |||||
| 2D gels | 7 | 10 | 12.4 | 9.3 | 5-30 | |||||
| Fragmentation | 33 | 10 | 9.5 | 5.2 | 1-21 | |||||
| Peptide synthesis 1-3 | 35 | 14 | 14. | 8.3 | 3-35 | |||||
| Peptide synthesis high | 11 | 7 | 8.0 | 4.9 | 2-15 | |||||
| Peptide purification | 29 | 7 | 8.7 | 6.8 | 2-30 | |||||
| Amino acid analysis | 30 | 5 | 6.0 | 5.2 | 0.5-21 | |||||
| CE | 10 | 2 | 4 | 6 | 1-21 | |||||
| HPLC | 15 | 3 | 5 | 5 | 1-21 | |||||
| Mass spectrometry | ||||||||||
| MALDI (mass) | 25 | 2 | 2.5 | 2.2 | 1-10 | |||||
| MALDI (sequence) | 5 | 3 | 5.2 | 5.1 | 2-14 | |||||
| Electrospray (mass) | 16 | 3 | 4.9 | 5.6 | 1-21 | |||||
| Electrospray triple quad | 12 | 5 | 7.4 | 4.8 | 3-15 | |||||
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The amount of time spent by responding laboratories on applications that were not directly related to customer services, including experiments performed to standardize instruments and methods development, could be categorized into three distinct groups: low (<6%), intermediate (14% to 30%), and high (>30%). In general, the low group was made up of DNA services (including DNA synthesis, oligonucleotide purification, template preparation, DNA sequencing, and microsatellite analysis), peptide synthesis and purification, and capillary electrophoresis. The intermediate group included several protein-based services: N-terminal protein sequencing and HPLC (15%) and electrospray (mass) mass spectrometry (18%). Amino acid analysis, protein fragmentation, SDS-PAGE, and 2D gel electrophoresis all required 25% to 30% of instrument time. The group that generally required the most time for nonuser runs was in the area of mass spectrometry, MALDI (mass), MALDI (sequencing), and electrospray (triple-quad) mass spectrometry.
The number of principal investigators using an individual service ranged from 1 to 400 (Table 4). In this survey, a principal investigator was defined as the head of a laboratory, so that several clients from the same laboratory would not be individually counted. The greatest number of principal investigators on average were reported for high-throughput DNA synthesis (154), low-throughput DNA synthesis (93), DNA sequencing (101), and triple-quad electrospray mass spectrometry (99).
TABLE 4
Principal Investigators Using Each Service per Facility
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| Principal Investigators | ||||||||||
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| Service | N | Median | Mean | SD | Range | |||||
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| DNA services | ||||||||||
| DNA synthesis 1-4 | 27 | 60 | 93 | 101 | 12-400 | |||||
| DNA synthesis high | 6 | 95.5 | 155 | 126 | 50-367 | |||||
| DNA oligo purification | 13 | 25 | 65 | 107 | 1-400 | |||||
| Template prep | 5 | 5 | 72 | 108 | 1-250 | |||||
| DNA sequencing | 29 | 70 | 100 | 94 | 3-400 | |||||
| Microsatellite analysis | 11 | 4 | 5.1 | 4.4 | 1-16 | |||||
| Protein services | ||||||||||
| N-terminal protein seq | 46 | 20 | 28 | 21 | 3-108 | |||||
| SDS-PAGE | 16 | 7.5 | 11 | 9 | 3-35 | |||||
| 2D gels | 9 | 7 | 9 | 8 | 1-30 | |||||
| Fragmentation | 31 | 10 | 13 | 13 | 1-50 | |||||
| Peptide synthesis 1-3 | 34 | 20 | 21 | 13 | 1-57 | |||||
| Peptide synthesis high | 11 | 30 | 31 | 29 | 5-89 | |||||
| Peptide purification | 31 | 17 | 20 | 19 | 1-78 | |||||
| Amino acid analysis | 29 | 19 | 27 | 34 | 1-175 | |||||
| CE | 11 | 4 | 32 | 75 | 1-250 | |||||
| HPLC | 18 | 5.5 | 18 | 40 | 2-170 | |||||
| Mass spectrometry | ||||||||||
| MALDI (mass) | 24 | 15 | 34 | 55 | 1-250 | |||||
| MALDI (sequence) | 5 | 3 | 13 | 17 | 1-40 | |||||
| Electrospray (mass) | 14 | 17 | 31 | 33 | 5-122 | |||||
| Electrospray triple quad | 11 | 20 | 99 | 242 | 5-824 | |||||
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Comparing the number of principal investigators using each service in 1998 to 1992, the largest increases were seen in capillary electrophoresis (20-fold), DNA sequencing and template preparation (6-fold), HPLC (4-fold), and low-throughput DNA synthesis and peptide purification (2-fold). The average number of principal investigators did not decrease between 1992 and 1998 for any service.
The average core facility in 1998 had 3.1 full-time personnel. In 1992, 4.1 full-time personnel were reported,4 and in 1987, about three full-time personnel were reported.2 In general, in 1998, a facility had a director plus two full-time and one part-time staff members. In a typical facility, approximately 25% of the staff had a Ph.D. degree, 21% had a master's degree, 33% had a bachelor's degree, and 21% had another degree. In 1987, a typical facility reported that 25% of the staff had a Ph.D. degree, 21% had a master's degree, 50% had a bachelor's degree, and 5% or less had another degree.
In 1998, 54 of the 81 reporting facilities were made up of staff with one director, all of whom worked on providing services. In seven facilities, no director was reported. In four facilities, more than two directors were reported, each in charge of different services. Another eight facilities were made up of only one director, each with no other staff. Assessing how directors spend their time showed that directors in eight facilities did only administrative work and did not work directly on services. In 41 of the 81 reporting facilities, directors reported spending 27% of their time on N-terminal protein sequence analysis. The other most common services on which directors worked were protein sample preparation (26 facilities), mass spectrometry (25), DNA sequencing (23), and peptide synthesis (23). On average, directors spent 75% of their time in the laboratory or on laboratory-related issues and 25% of their time on administrative work.
Services with the highest number of full-time staff (Table 5) were DNA sequencing (1.25) and DNA synthesis (1.0). Services that required 0.6 to 0.9 staff included peptide synthesis, mass spectrometry, and protein sequencing. Protein sequence sample preparation, DNA template preparation, amino acid analysis, microsatellite analysis, capillary electrophoresis, and administration each employed 0.3 to 0.5 staff members. Services that had the most part-time assistants (50%) included peptide synthesis and DNA sequencing. Other services had part-time assistance in the 20% to 30% range.
TABLE 5
Full-Time Staff Requirements for Each Service
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| Service | N | Mean | SD | |||
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| DNA services | ||||||
| DNA synthesis | 29 | 1.01 | 1.02 | |||
| Template prep | 7 | 0.52 | 0.61 | |||
| DNA sequencing | 30 | 1.25 | 0.92 | |||
| Microsatellite analysis | 10 | 0.45 | 0.59 | |||
| Protein services | ||||||
| N-terminal protein seq | 36 | 0.59 | 0.52 | |||
| Protein sample prep | 29 | 0.53 | 0.64 | |||
| Peptide synthesis | 34 | 0.79 | 0.66 | |||
| Amino acid analysis | 27 | 0.49 | 0.59 | |||
| CE | 8 | 0.33 | 0.68 | |||
| Mass spectrometry | 31 | 0.81 | 0.74 | |||
| Administration | 32 | 0.50 | 0.66 | |||
| Other | 14 | 0.81 | 1.02 | |||
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The average total space occupied by a core facility is 1090 ft2 (Table 6), which is not significantly greater than the 959 ft2 reported in the 1992 survey. This space is used for instrumentation, sample preparation, office, and consultation. A number of services received increased space allocations compared with 1992.4 These included a 1.8-fold increase in space for DNA sequencing and a 1.6-fold increase in mass spectrometry space. Space allocated to peptide synthesis increased 55%, and space allocated to DNA synthesis increased 26%. Apparently, those laboratories that continue to provide DNA synthesis and peptide synthesis have become larger perhaps because smaller ones have stopped offering these services.
TABLE 6
Space Requirements for Services
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| Square Feet | ||||||||
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| Service | N | Mean | SD | Range | ||||
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| DNA services | ||||||||
| DNA synthesis | 32 | 188 | 242 | 6-1000 | ||||
| Template prep | 10 | 135 | 200 | 6-588 | ||||
| DNA sequencing | 32 | 288 | 260 | 32-117 | ||||
| Microsatellite analysis | 8 | 111 | 114 | 4-352 | ||||
| Protein services | ||||||||
| N-terminal protein seq | 54 | 173 | 202 | 20-1250 | ||||
| Protein sample prep | 44 | 106 | 94 | 2-500 | ||||
| Peptide synthesis | 37 | 248 | 218 | 7-1000 | ||||
| Amino acid analysis | 36 | 104 | 93 | 10-500 | ||||
| Mass spectrometry | 31 | 254 | 279 | 20-1250 | ||||
| Miscellaneous | ||||||||
| Office | 71 | 171 | 158 | 16-887 | ||||
| Consultation | 15 | 73 | 56 | 20-200 | ||||
| Support | 67 | 158 | 139 | 4-720 | ||||
| Other | 25 | 307 | 370 | 10-1580 | ||||
| Average total area per lab | 79 | 1091 | 885 | 100-4750 | ||||
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The remaining services remained unchanged or experienced declines in space allocation. Space allocated to carbohydrate analysis, capillary electrophoresis, and amino acid analysis all declined (60%, 32%, and 14%, respectively). The amount of office space remains, on average, 171 ft2. Consultation space declined from 93 ft2 in 1992 to 73 ft2 in 1998, and support space averaged 139 ft2. The "Other" category averaged 370 ft2 and included the wide range of nonstandard uses listed in the section on Technical Capabilities (eg, fermentation, solution interactions), as well as cold rooms, hoods, and storage.
This survey also included questions regarding space allocated to a number of new services including DNA template preparation (135 ft2), protein sequence sample preparation (106 ft2), microsatellite analysis (111 ft2), and bioinformatics (84 ft2).
Balancing operational expenses and funding sources is critical to the service level that a facility can provide its users. Fifty of the responding laboratories provided some financial data, and of these, 47 provided information on income and 48 on expenditures. Thirty-five of the responding laboratories were from academia, 13 from research institutes, 11 from companies, and 1 from government. The data from nonprofit laboratories (ie, universities, research institutions, and government) were pooled for statistical purposes. Because there were few responses from industry, these data were not sufficient for statistical analysis, and the data are not given in the tables.
The overall operating expenses from 41 nonprofit laboratories averaged $257,800 ± $182,500 (median, $177,700) and ranged from $55,000 to $641,000. The overall operating expenses, broken down into subcategories, are detailed in Table 7. A comparison with data from the 1992 survey4 revealed that only the total figure of $257,800 for overall operating expenses, not the totals for individual categories, was significantly different (P = 0.001).
TABLE 7
Overall Operating Expenses
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| Thousands of U.S. Dollars | ||||||||||
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| Expense | N | Median | Mean | SD | Range | |||||
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| Supplies/reagents | 40 | 50.0 | 99.1 | 93.5 | 9.2-350.0 | |||||
| Service/repairs | 39 | 16.4 | 22.9 | 19.1 | 2.0-88.0 | |||||
| Depreciation | 6 | 30 | 34.8 | 23.9 | 10.0-70.0 | |||||
| Salaries | 39 | 104.0 | 138.5 | 103.0 | 1.0-28.0 | |||||
| Professional development | 25 | 2.2 | 4.1 | 3.5 | 1.0-15.0 | |||||
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Income to cover operating expenses is obtained by core laboratories from several different sources, including user fees, federal grants, grants from nonfederal sources, and institutional support. Total income was $293,470 ± $228,510 (median, $225,000; minimum, $10,000; maximum, $998,000). This was not significantly different from the 1992 survey finding.
User fees accounted for an average of $151,000 of income. Nine of the laboratories reported that they recover 100% of their costs from user fee income. However, from our recalculations based on the information furnished in the survey, it appears that only four of the nine actually recover all of their costs from user fee income, which ranged from $170,000 to $398,000. Of the laboratories at full recovery, all but one, which was exclusively a DNA sequencing laboratory, offered protein sequencing, three offered some type of mass spectrometry, and one offered no DNA services. This contrasts with the findings in 1992, when the two laboratories that recovered all of their costs from user fees were predominantly DNA-oriented facilities. Among all of the respondents, user fee income ranged from $170,000 to $860,000, which in some cases was not all of the income but at least covered the amount reported for total expenses (excluding instrumentation). Expenses ranged from $150,000 to $865,000 (one outlier of $2,174,000 was excluded from the data set).
Seventeen facilities of the 47 respondents were partially supported from federal grants. Fifteen of these facilities received an average of $75,700 6 $46,800 (median, $77,000) for noncapital expenses, such as reagents and salaries. Ten of the facilities also obtained federal funding for capital equipment, averaging $181,500 ± $159,000 (median, $130,000), ranging between $30,000 and $500,000. This shows federal support for instrumentation in core facilities, probably through instrumentation acquisition granting programs. Only five facilities reported grant funds from nonfederal sources.
Thirty-two core laboratories of the 47 received institutional support. Of these, 31 received support for operating expenses averaging $116,300. Twelve laboratories also received institutional support for capital equipment averaging $112,200. Six laboratories reported income from the Howard Hughes Medical Institute (HHMI). Three received HHMI support for their general operating budgets (primarily salaries), and all six received funds for capital equipment (average, $117,500 ± $110,900; median, $157,600). Nine laboratories received funding from diverse other sources; six of these were for operating expenses averaging $141,600 ± $79,800 (median, $145,000) and three for capital equipment.
The amount of income generated by user fees for any service depends on sample through-put and charges for the services. Sixty-nine of the responding laboratories provided information on charges for one or more services offered. Academic (43) or research institute (14) facilities made up the bulk of the respondents, with the remainder being companies (3) and a government facility (1). Eight respondents did not specify their type of facility. Table 8 shows the range of in-house charges for services across all facilities. The highest flat-rate charges were for MS/MS protein sequencing ($223/sample), protein fragmentation and isolation ($198), 2D gels ($178), and peptide purification ($135). The least expensive services included DNA template preparation ($12) and microsatellite analysis ($6.60). DNA sequencing cost about $16 per sample.
TABLE 8
In-House Charges for Services
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| Setup Charges (Dollars) | Per-Cycle Charges (Dollars) | |||||||||||||||||||
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| Service | N | Median | Mean | SD | Range | N | Median | Mean | SD | Range | ||||||||||
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| DNA services | ||||||||||||||||||||
| DNA synthesis | ||||||||||||||||||||
| 40-50 nmol | 7 | 5.0 | 6.6 | 3.2 | 4-12 | 24 | 1.0 | 1.0 | 0.3 | 0.2-1.5 | ||||||||||
| 0.2 µmol | 9 | 7.0 | 7.8 | 3.5 | 4-14 | 25 | 1.5 | 1.6 | 0.5 | 0.8-2.7 | ||||||||||
| DNA oligo purification | ||||||||||||||||||||
| 40-50 nmol | 13 | 10 | 17 | 13 | 1-50 | |||||||||||||||
| 0.2 µmol | 19 | 15 | 21 | 18 | 2-60 | |||||||||||||||
| Template prep | 5 | 7 | 12 | 13 | 4-35 | |||||||||||||||
| DNA sequencing | 29 | 15 | 16 | 8 | 2-37 | |||||||||||||||
| Microsatellite analysis | 8 | 2.5 | 6.6 | 7.6 | 2-24 | |||||||||||||||
| Protein services | ||||||||||||||||||||
| N-terminal protein seq | ||||||||||||||||||||
| <500 fmol | 12 | 82 | 121 | 127 | 30-500 | 14 | 15 | 17 | 11 | 4-37 | ||||||||||
| >500 fmol | 36 | 86 | 104 | 85 | 10-500 | 42 | 12 | 16 | 12 | 3-62 | ||||||||||
| SDS-PAGE | 10 | 58 | 81 | 64 | 16-220 | |||||||||||||||
| 2D gels | 6 | 138 | 178 | 168 | 46-500 | |||||||||||||||
| Fragmentation | 26 | 150 | 198 | 177 | 10-750 | |||||||||||||||
| Peptide synthesis | ||||||||||||||||||||
| 5-25 µmol | 10 | 79 | 102 | 90 | 25-315 | 16 | 12 | 13 | 6 | 1-25 | ||||||||||
| 0.1 mmol | 13 | 75 | 104 | 125 | 25-500 | 20 | 20 | 21 | 10 | 9-41 | ||||||||||
| 0.25 mmol | 16 | 100 | 142 | 111 | 25-450 | 25 | 30 | 35 | 18 | 10-90 | ||||||||||
| Peptide purification | ||||||||||||||||||||
| 5-25 µmol | 12 | 125 | 133 | 109 | 23-300 | |||||||||||||||
| 0.1 mmol | 16 | 100 | 135 | 94 | 23-300 | |||||||||||||||
| 0.25 mmol | 19 | 150 | 138 | 93 | 23-300 | |||||||||||||||
| Amino acid analysis | 24 | 32 | 39 | 22 | 11-97 | |||||||||||||||
| HPLC | 18 | 50 | 79 | 74 | 8-250 | |||||||||||||||
| Mass spectrometry | ||||||||||||||||||||
| MALDI (mass) | 20 | 25 | 31 | 20 | 8-85 | |||||||||||||||
| Electrospray (mass) | 12 | 40 | 52 | 42 | 20-180 | |||||||||||||||
| MS/MS protein seq | 6 | 125 | 223 | 222 | 40-500 | |||||||||||||||
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Many facilities assessed set-up fees as well as per-cycle fees for peptide synthesis, N-terminal Edman protein sequence analysis, and DNA synthesis. The total charges (set-up and per cycle fees) varied considerably across facilities. For example, synthesis of a 25-mer peptide at the 5- to 25-µmol scale ranged from $50 to $765, with an average of $351. Likewise, synthesis of a 25-mer oligonucleotide at the 40- to 50-nmol scale varied from $8 to $38, with an average cost of $27. N-terminal protein sequence analysis for 25 amino acids above the 500-fmol scale ranged from $50 to $1650, with an average cost of $505. This wide variation undoubtedly reflects the percent of costs that each facility must recover.
The charges for synthesizing peptides and oligonucleotides have decreased considerably from 1992 prices, when the average charge to synthesize a 25-mer peptide was $978 and the average charge for a 25-mer oligonucleotide was $93. The charges, however, for sequencing proteins by Edman chemistry have not changed significantly; the 1992 average charge to sequence 25 amino acids was $427.
Several facilities reported charging higher rates for outside users. Nonprofit facilities charged on average 60% more for outside users, and for-profit facilities charged 91% more. This latter figure is a significant drop (P < 0.005) from the additional 159% reported by for-profit users in 1992. On the extreme, in 1998 some facilities reported charging as high as three times the in-house rate.
How well each service provided cost recovery, including staff salaries, instrument maintenance, and depreciation and reagent costs, for that service is reported in Table 9. A cluster of services (ie, DNA synthesis, DNA purification, DNA sequencing, HPLC, and synthetic peptide purification) all reported an average of 80% to 100% cost recovery. The lowest average cost recovery value was reported for electrospray (mass) mass spectrometry (35%). For each service at least one laboratory reported that they recovered 100% of the cost of performing that service.
TABLE 9
Cost Recovery for Services
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| Cost Recovery (%) | ||||||||||
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| Service | N | Median | Mean | SD | Range | |||||
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| DNA services | ||||||||||
| DNA synthesis 1-4 | 24 | 95 | 85 | 27 | 21-150 | |||||
| DNA synthesis high | 6 | 80 | 80 | 17 | 60-100 | |||||
| DNA oligo purification | 11 | 100 | 94 | 24 | 60-150 | |||||
| DNA sequencing | 25 | 100 | 88 | 25 | 20-150 | |||||
| Microsatellite analysis | 9 | 70 | 63 | 34 | 10-100 | |||||
| Protein services | ||||||||||
| N-terminal protein seq | 41 | 50 | 59 | 32 | 5-115 | |||||
| SDS-PAGE | 10 | 63 | 63 | 42 | 5-120 | |||||
| 2D gels | 8 | 50 | 52 | 33 | 5-100 | |||||
| Fragmentation | 26 | 50 | 57 | 32 | 5-120 | |||||
| Peptide synthesis 1-3 | 29 | 75 | 67 | 33 | 40-120 | |||||
| Peptide synthesis high | 9 | 70 | 71 | 27 | 30-100 | |||||
| Peptide purification | 24 | 90 | 79 | 31 | 10-140 | |||||
| Amino acid analysis | 25 | 65 | 67 | 32 | 8-120 | |||||
| CE | 7 | 50 | 55 | 35 | 20-100 | |||||
| HPLC | 16 | 100 | 85 | 50 | 1-230 | |||||
| Mass spectrometry | ||||||||||
| MALDI (mass) | 19 | 60 | 61 | 36 | 5-100 | |||||
| MALDI (sequence) | 4 | 62 | 59 | 38 | 10-100 | |||||
| Electrospray (mass) | 11 | 30 | 35 | 29 | 5-100 | |||||
| Electrospray triple quad | 8 | 50 | 53 | 36 | 8-100 | |||||
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Using sample through-put data and charges provided by each laboratory, we calculated the expected user fee income for each laboratory. From this calculation, we found that user income data provided by respondents averaged 72% ± 57% of the calculated value (median, 69%; range, 0.7% to 207%), suggesting that a number of samples are processed by a laboratory for control purposes, and these do not generate income.
Biotechnology core laboratories continue to service the research community with a variety of protein and DNA services required for advances in proteomics and genomics. Except for a few laboratories that are totally self-sufficient, core facilities for the most part continue to be subsidized as reflected in the range (35% to 94%) of average cost recovery for services. In return, researchers obtain highly skilled services, with relatively quick turnaround times. Far from being static, the modern facility continues to add new services. For example, in the past 5 years, 2D gel electrophoresis, microsatellite analysis, C-terminal protein sequencing, and all aspects of mass spectrometry have appeared in several facilities. Upcoming services include optical biosensors, gene chip microarray technology, and quantitation by real time PCR. A few laboratories are offering analytical services at the GLP level. This will be an important trend to follow into the future.
The modern biotechnology core facility continues to offer selected services from a set of standard services. These include N-terminal protein sequencing, fragmentation of proteins for internal sequencing, amino acid analysis, peptide synthesis, HPLC separation of proteins and fragments, DNA synthesis, and DNA sequencing. These standard services were also available at biotechnology core facilities in 1992, when the previous survey was conducted.
We wish to thank Jose Gutierrez of the Scripps Research Institute for his role in the data collection for this survey and all of the members of the ABRF who responded to the survey.
1. Niece RL, Williams K, Naeve C. Professional Societies, Association of Biomolecular Resource Facilities. In Flickinger MC, Drew SW (eds): Encyclopedia of Bioprocess Technology. New York: John Wiley & Sons, 1999:2089-2120.
2. Williams KR, Niece RL, Atherton D, Fowler AV, Kutny R, Smith AJ. The size, operation, and technical capabilities of protein and nucleic acid core facilities. FASEB J 1988;2:3124-3130.
3. Niece RL, Beach CM, Cook RF, Hathaway GM, Williams KR. State-of-the-art biomolecular core facilities: a comprehensive survey. FASEB J 1991;5:2756-2760. [Erratum appears in FASEB J 1992;6:792.]
4. Ivanetich KR, Niece RL, Rohde M, Fowler E, Hayes TK. Biotechnology Core Facilities: trends and update. FASEB J 1993;7:1109-1114.