While experiment design and analytical methods play a crucial role in successful studies, the importance of biological sample integrity should not be overlooked, as it is critical to generating accurate and reliable results. Poor biospecimen quality can undermine well-planned research protocols, resulting in irreproducible and invalid outcomes, wasted time and resources, and even failed studies. That’s why biospecimen integrity is the cornerstone of reproducible, high-impact biomedical research, underpinning every stage of a study, from collection and storage through to processing and data integration.
Unfortunately, each of these steps is vulnerable to errors. To avoid generating erroneous results and jeopardizing patient safety, research teams can draw on the expertise of organizations like Crown Bioscience which provide the rigorously controlled, high-quality biospecimens required to meet the demands of modern, precision research, including biomarker discovery, oncology, and translational medicine.
This article highlights the five quality factors that research teams should be aware of, and that inform the comprehensive biospecimen protocols at Crown Bioscience.
1. Pre-analytical variables: the foundation of sample integrity
Rigorous sample controls start well before any laboratory analysis begins. Time to processing, temperature fluctuations, fixation methods, and handling procedures are among the most critical, and often overlooked, preanalytical variables. One study revealed that up to 70% of laboratory errors were caused by preanalytical errors that occurred during processes like manual handling outside the laboratory.
Delicate samples are vulnerable to contamination from dust and other materials, as well as cross-contamination from other samples. Additionally, temperature changes, delays, UV light, inconsistent protocols, or chemical or biological changes (e.g. pH, oxidation, microbial growth) can cause samples to degrade. Contaminated or degraded samples can mask real results while generating false ones, undermining entire studies. For example, with RNA- or protein-based assays, degradation begins rapidly if conditions aren’t optimized. RNA is particularly sensitive to warm and cold ischemic durations, cellular stress responses, tissue processing protocols, and storage conditions, which can compromise expression studies and biomarker validation.
Correctly following strict Standard Operating Procedures (SOPs) for sample collection and handling reduces variability and the potential for contamination or degradation. One study showed that correcting poor laboratory processes reduced contamination by infusion fluids from 20.6% to 1.9%.
This is why Crown Bioscience implements stringent pre-analytical controls to ensure the molecular and morphological profiles of every sample are preserved, so research teams can be confident in their study results.
2. Storage conditions and long-term viability
Storage conditions, such as light and humidity, as well as the duration of storage, can also negatively impact sample quality, particularly the stability of nucleic acids and proteins. While ultra-low temperatures and liquid nitrogen-based storage help preserve the biomolecular integrity of samples, consistency is also key. Fluctuations can occur during equipment failures or even routine sample access, causing samples to thaw and refreeze. Over time, these freeze-thaw cycles can cause samples to degrade or lead to inconsistencies between batches. One recent study, for example, demonstrated that freeze-thaw cycles resulted in significant protein degradation in plasma samples used for mass spectrometry-based biomarker discovery.
Recent high-profile cold storage failures are believed to have destroyed decades of research. This reiterates the importance of storing biospecimens in quality-controlled repositories where conditions are continuously monitored and backed up with emergency response protocols. All of Crown Bioscience’s storage infrastructures are fully validated to ensure the long-term viability of biospecimens and are backed up with comprehensive monitoring and fail-safe systems to protect the long-term quality of every sample.
3. Biospecimen characterization and annotation
Collecting detailed information about biological samples is key to understanding their makeup, quality, and characteristics before studies begin. By understanding the condition of a sample, including factors such as RNA integrity or DNA purity, research teams can confirm whether samples are suitable for precision medicine. While understanding the implications of different preservation methods enables them to select the most suitable sample for their requirements. For example, choosing between formalin-fixed, paraffin-embedded (FFPE) or fresh-frozen specimens depends on their downstream applications and the molecular targets being studied.
For oncology research teams, comprehensive preclinical annotation is critical. Only when this is in place can these teams successfully correlate their findings with clinical phenotypes and patient outcomes. Complete characterization and annotation give teams greater insight into how different regions within heterogeneous tumors respond to treatments, how subtle biomarkers may influence the efficacy of treatments, and what mechanisms of action or resistance may be at play. What’s more, recording full patient histories and outcomes improves patient stratification and ensures meaningful subgroup analyses can be completed.
This detailed annotation enhances biological specimens, making them powerful research tools. While this has always been true, the rise of AI and machine learning is making this ever more imperative. AI models rely on rich, multi-faceted data to create accurate predictions. As models become more sophisticated, extensive metadata will become exponentially more valuable because these models can extract subtle patterns and relationships that were previously undetectable.
4. Fit-for-purpose sample selection
Protecting the quality of biospecimens is essential, but even the highest-quality samples aren’t suitable for every assay. Application-specific quality control (QC) is also critical for successful studies. This is because a specimen that performs well in one application may not be suitable for another, even if strict quality protocols have been followed. For example, next-generation sequencing (NGS) requires intact nucleic acids, while immunohistochemistry (IHC) demands preserved morphology.
Failing to match biospecimen characteristics and downstream applications will increase study failure rates. This can occur when teams focus solely on sample quality without considering application requirements. To avoid this, research teams can work with organizations like Crown Bioscience that work closely with individuals to match sample attributes to their intended uses, increasing reproducibility and the chances of study success.
5. Ethical sourcing and regulatory compliance
Ethical sourcing, informed consent, and alignment with regulatory frameworks such as GDPR, HIPAA, and other local requirements must also be embedded into the foundations of any biospecimen research. This ensures that the appropriate oversight and accountability are in place, while protecting the integrity of the research and the individuals involved. Importantly, they also safeguard the rights of any participants taking part in the study. Regulatory frameworks that call for transparency in sourcing and documentation are designed to remove possible biases from studies and ensure study results are reproducible. Adhering to these ethical and regulatory directives builds trust with research participants, review boards, and the wider scientific community.
Lack of proper compliance can invalidate results, which can delay regulatory submissions or even lead to the termination of a study altogether. Additionally, teams that fail to comply with regulations may negate years of research and damage their professional reputations. It’s important to remember that the cost of a failed phase III trial includes all the costs associated with prior stages and finding a viable alternative.
What’s more, protocol compliance is being increasingly stressed by regulatory agencies, meaning this is set to become an increasingly important consideration when applying for drug approvals or designing clinical trials. With this in mind, Crown Bioscience ensures that all their biospecimens are ethically sourced and IRB-approved, with traceable documentation available for every sample.
Conclusion
Biospecimen integrity is essential for generating accurate and reliable results that are reproducible and translatable. This begins long before the start of preclinical studies and is a key consideration at every study phase. Research teams must successfully navigate multiple and varied procedures and regulatory frameworks to ensure study success.
Organizations like Crown Bioscience play a key role when it comes to the creation, handling, storage, and characterization of high-quality samples that research teams can trust, helping to enhance research outcomes, protect teams’ reputations, safeguard the rights of study participants, and build trust across the wider scientific community.
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