Professor Berthold Huppertz from Biobank Graz, highlights the importance of maintaining high sample quality in biobanking
The emerging new ISO standards for the pre-analytical handling of samples in biobanking give hope that sample quality can be much better maintained and documented. This, of course, should lead to improvement of patient care. However, where do you find the link between improving the pre-analytical pathway of sample handling in biobanks and improved patient care?
Overview on the pre-analytical pathway
For any analysis of a human sample, independent of whether this analysis is performed in a research setting or in a clinical routine setting, the sample needs to be taken from the body, transported, processed, may be stored and used for analysis.
Let’s take a blood sample as an example. Blood drawing normally takes place in a clinical setting using standard equipment resulting in the receipt of some millilitres of blood in a primary blood tube. In a clinical setting, this primary blood tube is then standing in the clinical ward for a while, transported to a (central) laboratory where processing and analysis take place.
In a research and biobanking setting, this primary blood will again be taken in a clinical setting, standing in the ward and then is transported to a lab or biobank. Here, the blood is processed, then divided into smaller aliquots, stored (short-term, mid-term or long-term) and subsequently distributed to be used for a research analysis.
This seems to be an easy path and the question is why there is the need to develop ISO standards for this. To give an answer here, we need to go into detail into this pathway.
The pre-analytical pathway in detail
1. Blood drawing procedure
The person performing the venepuncture needs to have a specialisation and respective training not to harm the donor. Hence, it needs to be documented who has performed the venepuncture and what instruments have been used.
2. Labelling of primary blood tube
Not only the person performing the venepuncture, also the donor needs to be identified. Of course, there is no need to have names and direct person-related data. Codes and identification numbers are sufficient. Therefore, the primary blood tube containing the blood of the donor must be specifically and uniquely labelled to provide a clear link between donor, primary blood tube and blood sample.
3. Time of blood drawing
As soon as the blood sample has left the body of the donor, the sample is present in a different environment: There is no longer flow of blood, the temperature has changed, light is present and the surrounding changed from living cells communicating with the blood cells to a plastic tube. Hence, it is important to document the time of blood drawing to know when the change of environment started.
4. Duration and conditions of sample transport
After blood drawing, the sample is normally placed in a rack together with other samples and waits to be transported to the laboratory. At that time, the sample is still alive and will adapt to the changes of its environment (temperature, light etc.). To give an example: The cells sense lower temperature and stop of blood flow and will react with increasing their level of stress proteins as in the body both conditions are extremely harmful. The longer the samples are staying in the rack the more changes within the sample will occur. This is true for the time the sample is staying in the clinical ward as well as for the time the sample is transported to the laboratory. Hence, documentation of times and temperatures are essential.
Documentation of the arrival time at the biobank is needed to calculate the duration of sample transport. The sample will be processed according to the protocols of the biobank and divided into smaller aliquots. These aliquots will be taken from a single sample and thus allow multiple different analyses of the same sample without freeze-thawing the sample multiple time. The aliquots are then frozen and stored at minus 80°C or lower until use. Documentation of each step during processing and storage is mandatory for a biobank.
Finally, the primary blood sample will be distributed and send to a laboratory, where the analysis will take place. Within the laboratory, the sample will be further processed depending on the needs of the analysis, the analysis will be performed and the respective results will be used to increase knowledge.
The pre-analytical pathway today
Today, there is quite some variability between biobanks and hospitals in the documentation details of the pathway described above. In some hospitals, all or nearly all the steps are documented as described, while in other hospitals only some or few of the steps are documented. Hence, depending on the hospital setting, sometimes only little data on the pre-analytical pathway can be retrieved for subsequent analysis.
This discrepancy has a major negative impact on research results – and hence on patient care. If biobanked samples are used for analysis, they should be comparable in terms of handling, timing, temperatures, processing etc. If some samples are used with 30 minutes while others are used only the day after blood drawing standing in a room or in the sun in summer or in the cold in winter, this will of course dramatically influence the content of the samples. Hence, there is massive variability in the analytical test results that is simply due to differences in the pre-analytical handling of the samples rather than due to differences between healthy and diseased donors.
The pre-analytical pathway tomorrow
The emerging ISO standards for biobanking will set the stage for improved documentation of the pre-analytical pathway. Hence, any variation not linked to the health status of the donor can be linked to variations in the pre-analytical handling of the samples.
This, of course, is not enough! What is needed is a much better understanding of the major impact, handling of samples has on the quality of results obtained with these samples. Hence, it is not only documentation that makes the difference, but rather a proper handling of the sample at each step of the pathway to optimally maintain its quality.
Only then, results from the clinical setting in combination with the results from the research setting can – without doubt – be directly linked to the health status of the donor.
This will have a direct and major positive impact on:
- Patient care in the clinical setting: no longer false positive or false negative results!
- Research on e.g. identification of new biomarkers for prediction: no longer massive variations in a cohort due to differences in sample handling!
- Development of new treatments and medication: no longer very time consuming pre-clinical testing due to missing comparability of samples!
Please note: this is a commercial profile
Professor Berthold Huppertz, PhD
Director and CEO
Head, Organisational Unit of Research Infrastructure
Medical University of Graz
Neue Stiftingtalstraße 2B/II
8010 Graz, Austria
Tel: +43 316 385-72716 (secretary)
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