An Overview of Pre-Analytical Factors Impacting Metabolomics Analyses of Blood Samples
Abstract
1. Introduction
2. Choice of Matrix
2.1. Serum vs. Plasma
2.2. Whole Blood and Dried Blood Spot Sampling
2.3. Recommendations
3. Pre-Processing Factors Impacting Metabolome Composition
3.1. Collection Tube Type
3.1.1. Sample Collection Tubes: Serum
3.1.2. Recommendations
3.1.3. Collection Tube Type: Plasma
3.1.4. Recommendations
3.2. Pre-Centrifugation Sample Handling
3.2.1. Persistent Cellular Metabolism
3.2.2. Time Delay
3.2.3. Pre-Centrifugation Temperature
3.2.4. Avoiding Hemolysis in Blood Sample Preparation
3.2.5. Recommendations
4. Centrifugation Conditions
Recommendations
5. Post-Centrifugation Processing Factors Impacting Metabolome Composition
5.1. Sample Stability over Time
5.2. Temperature
5.3. Recommendations
5.4. Freeze–Thaw Cycles
5.5. Recommendations
6. Sample Quality Control Markers
7. Recommendations for Bio-Banked Sample Labelling
8. Summary
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A
Author | Year | Methods | Main Findings |
---|---|---|---|
Liu et al. [22] | 2018 |
|
|
Yu et al. [23] | 2011 |
|
|
Denery et al. [24] | 2011 |
|
|
Kaluarachchi et al. [26] | 2018 |
|
|
Wedge et al. [30] | 2011 |
|
|
Kennedy et al. [34] | 2021 |
|
|
Liu et al. [27] | 2010 |
|
|
Barri et al. [25] | 2013 |
|
|
Vignoli et al. [28] | 2022 |
|
|
Bovo et al. [31] | 2023 |
|
|
Suarez-Diez et al. [29] | 2017 |
|
|
Blood Matrix | Tube Additive | Clotting Time | Impact on Metabolomics Testing |
---|---|---|---|
Serum | Thrombin | 5 min | |
Serum | Silicate | 30 min |
|
Serum | Non-additive | 60 min |
Anticoagulant | Anticoagulation Mechanism | Considerations for Metabolomics Work |
---|---|---|
Citrate | Calcium chelator | |
Ethylenediaminetetraacetic acid (EDTA) | Calcium chelator | |
Heparin | Thrombin inhibition |
|
Author | Year | Time Conditions | Temperature Conditions | Matrix | Significant Findings | Recommendations for Storage |
---|---|---|---|---|---|---|
Jobard et al. [69] | 2016 | 1 or 6 h time delay | RT or 4 °C (fridge) | Plasma and serum |
| <6 h at RT; 6 h at 4 °C acceptable |
Liu et al. [27] | 2010 | 1–4 h | 37° | Plasma and serum |
| <1 h at 37°; most changes occur during first 2 h of delay |
Nishummi et al. [73] | 2018 | RT: 0, 15, or 30 min Cold storage: 1, 4, or 8 h | RT or cold storage (Cube Cooler, Forte Grow Medical, Tochigi, Japan) | Plasma and serum |
| <30 min at RT; 1 h cold storage acceptable |
Nkuna et al. [76] | 2023 | 8, 12, 48, and 72 h | RT | Plasma and serum |
| <8 h at RT |
Ghini et al. [70] | 2022 | 30 min–72 h Protocols from multiple biobanks considered | RT or cold storage | Plasma and serum |
| <30 min time delay at RT; <72 h at 4 °C |
Wang et al. [82] | 2018 | 0, 15, 30, and 48 h | Cold storage (refrigerator) | Plasma |
| <15 h cold storage |
Breier et al. [74] | 2014 | 3 h, 6 h, and 24 h | RT and cold storage (cool pack) | Plasma and serum |
| <3 h cold storage |
Fliniaux et al. [71] | 2011 | 4 h or 24 h | RT or 4 °C | Serum |
| <4 h at RT; 24 h at 4 °C is acceptable |
Yin et al. [17] | 2013 | 2, 4, 8, and 24 h | RT and cold storage (ice water) | Plasma |
| <2 h at RT; up to 4 h cold storage is acceptable |
Trezzi et al. [79] | 2016 | 10, 30, 60 min, 3 h, or 23 h | RT or 4 °C | Plasma |
| <3 h cold storage |
Xiong et al. [93] | 2024 | 24 h | RT or 4°C | Plasma |
| Up to 24 h at 4 °C |
Killilea et al. [75] | 2024 | 1 h, 4 h, or 24 h | 4 °C, 20 °C, or 37 °C for 1 h | Plasma and serum |
| <4 h at RT or cold storage |
Liu et al. [22] | 2018 | 2 h or 4 h | RT or 4 °C (ice water) | Plasma |
| <4 h cold storage |
Seymour et al. [77] | 2011 | 0, 5, 10, 20, and 30 min | RT, cold storage 1 (ice pack), or cold storage 2 (wet ice) | Plasma |
| <5 min at RT; cold storage on wet ice preferred |
Jones et al. [78] | 2007 | 0, 3, 6, 9, 12, and 15 min | RT or cold storage (on ice) | Plasma |
| 15 min at RT or cold storage |
Clark et al. [83] | 2004 | 1, 2, 3, 4, and 7 days | RT or 4 °C | Plasma |
| RT and/or cold storage for several days is permissible |
Kamlage et al. [80] | 2014 | 2 h or 6 h | RT or cold storage (wet ice) | Plasma |
| <2 h cold storage |
Sens et al. [81] | 2023 | 20, 60, 120, and 240 min | RT or cold storage (ice water) | Plasma |
| 1 h cold storage |
Debik et al. [72] | 2022 | 30 min or 1, 2, 4, or 8 h | RT | Plasma and serum |
| <1 h RT storage |
Analytical Phase | Recommendation |
---|---|
Choice of matrix |
|
Serum collection tube |
|
Plasma collection tube |
|
Pre-centrifugation time and temperature |
|
Centrifugation |
|
Post-centrifugation time and temperature |
|
Freeze–thaw cycles |
|
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Thachil, A.; Wang, L.; Mandal, R.; Wishart, D.; Blydt-Hansen, T. An Overview of Pre-Analytical Factors Impacting Metabolomics Analyses of Blood Samples. Metabolites 2024, 14, 474. https://doi.org/10.3390/metabo14090474
Thachil A, Wang L, Mandal R, Wishart D, Blydt-Hansen T. An Overview of Pre-Analytical Factors Impacting Metabolomics Analyses of Blood Samples. Metabolites. 2024; 14(9):474. https://doi.org/10.3390/metabo14090474
Chicago/Turabian StyleThachil, Amy, Li Wang, Rupasri Mandal, David Wishart, and Tom Blydt-Hansen. 2024. "An Overview of Pre-Analytical Factors Impacting Metabolomics Analyses of Blood Samples" Metabolites 14, no. 9: 474. https://doi.org/10.3390/metabo14090474
APA StyleThachil, A., Wang, L., Mandal, R., Wishart, D., & Blydt-Hansen, T. (2024). An Overview of Pre-Analytical Factors Impacting Metabolomics Analyses of Blood Samples. Metabolites, 14(9), 474. https://doi.org/10.3390/metabo14090474