In this article we will look at how safe and correct storage of samples is crucial from the nascent stages of drug discovery to post-market surveillance and how Sampled’s biorepository services can play a pivotal role in advancing medical breakthroughs.

1. Role of biobanking in early Research and Development:

In the initial stages of drug discovery, researchers must rely on access to high-quality biological specimens to unravel the underlying mechanisms of diseases and identify potential therapeutic targets. Sampled’s biobanking infrastructure serves as a vital resource, enabling researchers to securely store and access a diverse array of samples, including:

• DNA/RNA
• Whole blood
• Serum
• Saliva
• Urine
• Stool
• Hair
• Cell pellets
• Protein Samples

By providing centralized storage facilities equipped with state-of-the-art preservation technologies, Sampled empowers researchers to accelerate the pace of discovery and validation of novel drug candidates as well as biomarker discovery. Furthermore, our secure facilities are monitored 24 hours a day, all year round with multiple backup power generators to ensure their security and integrity.

2. Preclinical Testing:

As drug candidates progress through preclinical testing, the demand for well-characterized biological samples becomes increasingly critical. Sampled holds both CAP and CLIA licenses so that our biorepository sample storage services facilitate the procurement and distribution of meticulously annotated specimens, thereby streamlining preclinical studies and enhancing the reproducibility of research outcomes. Additionally, by offering customizable sample management and biobanking solutions, Sampled enables researchers to optimize experimental protocols and improve the predictive value of preclinical models, ultimately reducing the risk of late-stage drug failures.

3. Clinical Trials:

Throughout the clinical trial phase, the availability of high-quality biospecimens is indispensable for assessing drug safety, efficacy, and pharmacokinetics. Sampled’s expertise in sample collection, processing, and biosample storage ensures compliance with stringent regulatory requirements while maintaining sample integrity and traceability. By leveraging Sampled’s comprehensive biobanking infrastructure, pharmaceutical companies can mitigate the logistical challenges associated with multi-site clinical trials, streamline sample logistics, and enhance data quality, thereby expediting the development timeline and reducing costs.

The ability to package, transport and store samples in a systematic and highly structured manner by following best practices gives researchers the confidence that their sample’s integrity is intact which means the data generated from them is accurate and reproducible. Furthermore, our ability to scale to meet your sample storage needs through every stage of your clinical trial means that you can focus on what matters most instead of setting up a new, or expanding an existing, biorepository. 

4. Post-Market Surveillance:

Even after a drug/therapeutic has been approved for market release, the need for continuous monitoring of safety and efficacy remains paramount. Sampled’s biobanking services extend beyond the realm of drug development and supports post-market surveillance initiatives aimed at detecting adverse drug reactions, monitoring long-term outcomes, and evaluating real-world effectiveness. By establishing longitudinal sample collections linked to comprehensive clinical data, Sampled empowers researchers to conduct retrospective analyses and identify emerging safety signals, thereby safeguarding public health and informing regulatory decision-making.

Similarly, another consideration to be made for pharmaceuticals is how their archived or legacy sample collections (perhaps through acquisitions or donations) are processed and stored. It is crucial that your documenting and SOPs for storing multiple sample collections is standardized across the entire collection so that sample integrity is prioritized but also so that they are categorized correctly. Failure to properly organize and maintain high uniform storage conditions can result in some sample collections being lost, mislabeled or destroyed by mistake.

In conclusion, Sampled’s biobanking services represent a cornerstone of the drug discovery pipeline, offering versatile solutions that span multiple stages of pharmaceutical research and development. By providing researchers with access to a wide range of storage solutions from ambient storage to -196°C Liquid Nitrogen tanks, coupled with robust infrastructure and tailored support services, Sampled accelerates the pace of innovation and fosters collaboration across the biomedical community. As the search for transformative therapies continues, Sampled remains committed to advancing precision medicine and driving the next wave of scientific breakthroughs.

If you would like to learn more about our Biobanking services, speak to one of our experts today

This blog aims to answer these two questions to introduce our Functional Quality Control (FQC) testing performed in our Global Integrated Analytical Biorepository (GIAB) to assess sample quality and validate subject identity.

What is FQC Testing?

In order to mitigate unforeseen errors during sample collection, transport and processing we perform FQC testing. An FQC test involves running a custom Genotyping SNP assay on every sample that is processed in our laboratory or enters our GIAB, in which DNA extraction is performed – this provides a range of benefits including:

• Our FQC assay serves as a quality check that provides confidence in the performance of the sample in downstream applications. This ensures that clients are not running assays with a high likelihood of failure – saving time and money.
• DNA fingerprinting enhances sample tracking as they undergo multiple processing steps – an added layer of security for potentially irreplaceable samples.
• Provides a concordance test to verify sample authenticity and manually collected patient phenotype.
• Verification that sample is from the same patient with longitudinal studies.
• Provides backstop for review if clients still want to run the sample – enabling a greater understanding through more data points.
• Helps to flag any external issues with collection, transportation, or handling – supporting standardization across large scale trials with multiple collection sites.

Essentially, FQC is the process by which we ensure that samples and data generated from their analysis are of a high enough standard to assure reliable and repeatable results with added benefits of security and sample damaging event flagging.

Why perform FQC Testing?

There are several reasons that make us advocate FQC testing to our clients, these include valid assays, financial viability, rich datasets, and sample identification:

Valid Assays

The primary purpose of running an assay is to gain insights from the results. The quality of the insight gained therefore is directly related to the assay being valid and providing reliable, accurate and reproducible results. Running our FQC test ensures that the samples being run in concordant tests are to the correct standard required for the assay to be valid.

Financial Viability

Many assays can be expensive to run, and long-term storage cost for future testing can also require a continued investment. Running an FQC test to inform how successful the assays are likely to be or whether the sample is worth storing can protect our clients’ investments and make the most of their budgets or research grants.

Rich Datasets

Despite FQC results, many clients opt to run samples that may have failed the FQC test anyway to ensure they are maximizing their opportunity during clinical trials. Samples that have failed during the assays can then be checked against the FQC data to determine if those particular results can be discounted from research. This provides rich datasets for researchers to draw upon during analysis.

Sample Identification

Running FQC gives us a DNA fingerprint (similar to forensic testing) of each sample, enabling an added layer of security in sample tracking. Unless clients opt for an alternative custom solution, we operate a standard of uniquely barcoded sample storage tubes and racks that are recorded against the sample in our LIMS platform – having a DNA fingerprint provides a redundant back up of the sample record that we can run a profile match against in our database.

Figure 1: Contaminated sample vs. uncontaminated sample.

Scatter Plot Key

The images above are typical scatter plot, each dot represents the genotype for one sample on that SNP.

Samples will typically cluster into 4 regions, indicative of the genotype at that locus (HOM= homozygous, HET = heterozygous): No Call (black), HOM A (green), HOM B (red), or HET (blue), enabling gender concordance to be established.

The image on the left is an example of a profile that was observed with a possible contamination, the grey dot between the green and blue clusters, clustering for the remaining SNPs for that sample would need to be checked to verify the status of that sample.

A failed run will not show these 4 clear clustering patterns.

Summary

FQC testing is performed to ensure reliable and repeatable valid assays through pre-qualification of samples ahead of more extensive and expensive testing. It also serves a number of other functions such as financial viability, rich datasets and sample identification.

The benefits of FQC testing assure that clients are getting not just high-quality research insights and security, but they are also able to maximize their budgets and grants through confidence in valid assays and future utilization of the samples after storage.

Learn more about how we can support your research whilst ensuring the potential of your precious samples is maximized, contact one of our experts today.

How does CRISPR gene editing work?

When CRISPR Cas9 protein is added to a cell, along with a strand of guide RNA, the Cas9 protein first binds to the guide RNA. This complex is then able to move along the DNA sequence until it locates a specific sequence of DNA (approximately 20 base pairs long) that matches the guide RNA. Once the complex locates the specific sequence or gene it was programmed to, it cuts the DNA before mutations are introduced to make precise changes to the DNA sequence. This can include removing the sequence or turning the genes on/off by changing the one letter of the DNA code to another.  

The promise of CRISPR technology is very exciting as the technology opens doors for groundbreaking changes to everyday life, including the prevention and treatment of many diseases, increasing crop yield and even editing out harmful genes within the DNA of fetuses.

So, what are the benefits of outsourcing CRISPR gene editing?

While some research institutions have developed in-house expertise in CRISPR gene editing, there are several compelling reasons why outsourcing these services can be beneficial. In this blog, we will explore some of the five reasons why outsourcing CRISPR gene editing services can be advantageous.

Access to specialized expertise

CRISPR gene editing is a complex and rapidly evolving technology that requires specialized expertise to execute with precision and accuracy. With CRISPR being a new technology, there is a lack of user friendly guides or resources to help researchers who wish to carry out CRISPR by themselves. This has led to scientists who are unfamiliar with protocols attempting their experiments several times before achieving some success, with many citing that the optimization step is particularly difficult to execute properly. The success achieved by the few who have managed to delete/insert genes is limited however, as editing efficiency is far lower than they would hope.

By repeating the same experiment several times, only to obtain low editing efficiency, researchers who have tried to execute CRISPR research are wasting not only time and resources but money too. Outsourcing gene editing services to a specialized service provider such as Sampled allows researchers to gain access to a team of experienced and knowledgeable experts with deep expertise in this field. We  are equipped with the latest gene editing tools and technologies, allowing us to deliver efficient and effective solutions for a wide range of gene editing applications.

Cost-effective solution

Outsourcing CRISPR gene editing services can be a cost-effective solution for research institutions and biotech companies. The cost of setting up an in-house gene editing laboratory can be high, as it requires significant investments in equipment, personnel, and training which can take a long time. By outsourcing gene editing services, institutions and companies can save on these costs and leverage the expertise of specialized service providers who have already made these investments.

Flexibility and scalability

Outsourcing CRISPR gene editing services to Sampled offers flexibility and scalability. We can quickly adapt to your project needs and timelines changing, providing researchers with the ability to scale up or down their gene editing projects as required. This flexibility can be particularly valuable in situations where resources are limited or where project timelines are subject to change.

Quality assurance

Outsourcing gene editing services can also provide researchers with quality assurance and peace of mind. Our tried and tested established protocols and quality control processes are in place to ensure that all gene editing projects are executed to the highest standards of accuracy, efficiency, and safety. By outsourcing gene editing services, researchers can be confident that their gene editing projects will be executed to the highest standards, providing reliable and reproducible results.

Regulatory compliance

CRISPR gene editing is subject to stringent regulatory compliance requirements, particularly when it comes to clinical trial research. By outsourcing gene editing services to a service provider that specializes in regulatory compliance, researchers can ensure that their projects meet all regulatory requirements and standards which in turn ensures your project won’t suffer delays. This can be particularly important for researchers seeking to develop new gene therapies or other clinical applications of CRISPR gene editing.

The benefits of outsourcing CRISPR gene editing work to Sampled

We accept induced pluripotent stem cells (iPSCs) directly from clients or those selected from repositories housed at Sampled such as National Institute of Mental Health (NIMH; https://www.nimhgenetics.org/) and the National Institute of Neurological Disorders and Stroke (NINDS; https://stemcells.nindsgenetics.org/). Our trained experts can discuss your needs and help with experimental design so that you can be assured that the cells to be edited meet your expectations. Furthermore, our cells undergo rigorous quality control testing to ensure that you will receive a 100% homogeneous population, this is crucial for investigations such as drug screening studies to minimize noise and prevent genetic drift within cell populations.

To summarize, outsourcing CRISPR gene editing services can provide many benefits to research institutions and biotech companies. By gaining access to specialized expertise, cost-effective solutions, flexibility, quality assurance, and regulatory compliance, researchers can execute their gene editing projects with confidence and achieve their desired outcomes, without having to become CRISPR experts overnight.

To get in touch with our experts and learn more about our Sampled Labs Services click here.

Why is Temperature Controlled Sample Storage Important for Research?

Temperature controlled and cryopreserved sample storage is vital for preserving the quality of samples, especially in fields such as biotechnology and life sciences. These samples often contain sensitive and perishable materials that can be easily damaged by changes in temperature. As a result, maintaining stable temperatures is crucial to prevent degradation and ensure that samples are suitable for analysis and future use.

In addition, many samples used in research must be stored at specific temperatures to remain biologically active. For example, samples that contain live cells or microorganisms must be stored at temperatures that mimic their natural environment to ensure their viability. In such cases, temperature fluctuations can quickly render the samples useless, making temperature control essential.

Options for Temperature Controlled Sample Storage

There are several options available for temperature-controlled sample storage, each with its advantages and disadvantages. These options can include; Cryogenic Storage, Ultra-Low Temperature Storage and Cold Room Storage.

Cryogenic storage:

Cryogenic storage involves freezing samples at extremely low temperatures (-196°C) using liquid nitrogen or other cooling agents. Cryogenic storage is ideal for long-term preservation and is commonly used for storing biological samples, such as blood, tissues, and cells.

Cryogenic storage can come with several challenges including; maintenance of equipment, automation reliability and capital expenditure could all be restrictive factors to consider.

Ultra-Low Temperature (ULT) Storage:

ULT storage involves storing samples at specific temperatures, such as -80°C. This type of storage is ideal for samples that require precise temperature control, such as vaccines, biopharmaceuticals, and biological samples.

Depending on the facilities available limiting factors can be resource and facilities related, the footprint taken up by manual or automated sample storage freezers can be restrictive in certain locations such as Boston, USA or Cambridge, UK. Automated systems can also present issues such as facilities requirements and a lack of system robustness.

Cold Room Storage:

Cold room storage typically involves storing samples at controlled temperatures between 2°C and 8°C. This type of storage is commonly used for samples that must be maintained at low temperatures for short periods, such as medical samples and pharma product.

Depending on volume stored, managing facilities for cold room storage can be less complex than lower temperatures, but when storing higher volumes specialized warehouses and buildings may be required – this could come with large capital expenditures and resource requirements.

Sample Storage Tubes

According to ISBER Best Practices, sample storage tubes should feature a barcode to enable tracking at the tube level.  This is often done using a 2D coded sample storage tube which is a type of laboratory sample container with a unique 2-dimensional barcode imprinted on it, this can be read by a barcode scanner to identify the contents of the tube. The barcode serves as a unique identifier that can be cross referenced within a Laboratory Information Management System (LIMS) such as SampledSphere information such as the sample name, date of storage, and other relevant details.

Using 2D coded sample storage tubes helps in efficient and accurate sample tracking, storage, and retrieval. They provide a reliable and convenient means of identification and reduce the risk of mix-ups or mislabeling of samples. Additionally, the use of barcodes helps automate the sample management process, reducing the manual effort and errors associated with manual tracking. This ensures that samples are properly stored and preserved for future use, and that research results are accurate and reliable.

That said, not all sample types can or should be stored in a sample tube – as an independent organization Sampled can work with many different labware suppliers and will always recommend the most appropriate primary storage vessel for your needs.

When looking at sample storage, there could be major benefits to working with a partner such as Sampled. As one of the worlds largest biorepositories and nearly 25 years’ experience in sample storage, if you have a sample, we can store it.

Conclusion

Temperature-controlled sample storage is an essential aspect of modern research and biotechnology. Whether you’re storing biological samples, chemicals, or other research materials, it’s crucial to maintain stable temperatures to ensure the integrity and accuracy of your samples. With the different options available, from cryogenic storage to refrigerated storage, and huge variety of primary storage vessels, researchers can choose the best solution for their specific needs and ensure that their samples are stored in a manner that is safe, secure, and suitable for future use.

Please reach out to our team today to learn how we can support your research.

PBMC Isolation begins with a sample of peripheral blood, the sample is then placed into a centrifuge, which spins the sample at high speed and separates the cells into two distinct populations. The heavier cells, such as red blood cells and platelets, are pushed to the bottom of the tube, while the lighter cells, such as mononuclear cells, are pushed to the top. The two populations of cells can then be collected separately, assessment can typically include monitoring yield and purity.

What are Common Applications?

Once the cells have been separated, PBMCs can be used for a variety of applications:

• Immuno-oncology
• Stem Cell Therapy / Regenerative Therapy
• Transplantation and Cell Therapy
• CAR-T Cell Therapy
• Autoimmune Disease & Diagnosis Research
• Biomarkers / Patient Stratification
• Toxicology
• Rare Disease Research

This process is complex and requires a blood draw, specialized equipment and expertise – all of which have specific requirements:

1. Blood Draw: The process of isolating PBMCs requires a blood draw. This blood draw must be performed in a sterile environment, and the blood must be processed quickly to avoid cell death.
2. Specialized Equipment: The isolation process itself is complex and requires specialized equipment, such as a Hamilton easyBlood.
3. Expertise: PBMC Isolation requires expertise in cell biology, these labs can be hard to find and difficult to establish, especially ones that have the necessary expertise. This could limits the availability of these services.

What is the Resource Investment?

PBMC Isolation, however, is an expensive process that requires a large amount of investment in resources including:

1. Materials and Reagents: a primary reason for the high cost of PBMC isolation is the materials and reagents used in the process. The isolation procedure involves multiple steps, including blood collection, separation of cells, and purification of the desired cell population. The reagents used in these steps are specialized and can be expensive. Additionally, the cost and availability of these reagents can fluctuate depending on supply and demand, leading to further fluctuations in the cost of PBMC isolation.
2. Expertise and Training: Another reason for the high cost of PBMC isolation is the expertise and training required for the technicians performing the procedure. PBMC isolation is a complex process that requires specialized skills and knowledge, and technicians need to be well-trained to ensure the quality and purity of the cells obtained. This requires investment in training and development, which can be costly for research organizations and laboratories.
3. Equipment and Infrastructure: The equipment and infrastructure needed to carry out PBMC isolation also contribute to the high cost of the procedure. The isolation process requires specialized laboratory equipment, including cell separators, centrifuges, and cell culture equipment. This equipment can be high capital expenditures, and ongoing maintenance and facilities costs can also be significant. Moreover, the need for specialized facilities, such as cell culture laboratories, can also drive up the overall cost of PBMC isolation.

If you require PBMC Isolation but are facing some or all of the above barriers, it may make sense to outsource to a partner lab that has established labs with economies of scale that you could benefit from. Read this blog to learn more about why outsourcing PBMC Isolation could work for you: Automated PBMC Isolation – 3 Compelling Reasons to Outsource.

In conclusion, PBMC isolation can be an expensive procedure due to the cost of materials and reagents, the expertise and training required, and the equipment and infrastructure needed. Despite the high cost, PBMC isolation remains a crucial component of medical research with a wide range of applications including Immuno-oncology, cellular therapies, toxicology and more.

To learn about our PBMC Isolation services, contact our team of experts today.

What are common application areas?

1. Gene Expression Analysis
2. Disease Diagnosis
3. Drug Discovery
4. RNA-based therapeutics
5. Forensics

Gene Expression Analysis

RNA extraction is used to study gene expression in cells, tissues, or whole organisms. By measuring the amount and type of RNA present in a sample, researchers can determine which genes are active or inactive and how they respond to different conditions or stimuli. This information can provide valuable insights into cellular processes, disease states, toxicity studies and drug responses.

Disease Diagnosis

RNA extraction is used in medical diagnostics to detect the presence of RNA viruses, such as SARS-CoV-2, Ebola virus and Hepatitis C. The RNA extracted from patient samples, via nasal swabs or blood samples, is analyzed to detect the presence of viral RNA. RNA extraction is also used to detect RNA molecules that are indicative of specific diseases, such as cancer. This is because RNA is thought to alter which proteins are produced, in cancer patients, these changes may lower levels of proteins that kill cancer cells or increase proteins that prompt a cancer cell to keep dividing. By identifying specific RNA markers, physicians can diagnose diseases earlier, monitor disease progression, and develop targeted therapies.

Drug Discovery

DNA extraction is a critical tool in drug discovery and development. By studying the RNA expression profiles of cells or tissues treated with various drugs, researchers can identify potential drug targets and evaluate the efficacy of different compounds. RNA extraction can also be used to identify biomarkers that can be used to predict drug responses or monitor disease progression in clinical trials.

RNA-based therapeutics

In recent years our understanding of RNA functions and their roles in diseases has led to the application of various RNAs to selectively function on “undruggable” proteins, transcripts and genes. By isolating and utilizing specific RNAs (such as mRNA) researchers are now able to broaden the therapeutic targets in disease states such as Duchenne muscular dystrophy, spinal muscular atrophy and COVID-19. Several RNA-based medications have been approved for clinical use, while others are still under investigation or preclinical trials.

Forensics

RNA extraction can be used in forensics to identify individuals based on their RNA profiles. RNA is an abundant molecule that can be extracted from various tissues, including hair, skin, and blood. By comparing RNA profiles between crime scene samples and suspect samples, forensic scientists can identify suspects or exonerate innocent individuals.

How is RNA Extraction Performed?

RNA extraction is a crucial process in molecular biology, genetics, and medicine, which involves isolating and purifying RNA from biological samples such as cells or tissues. Obtaining high-quality RNA is often the first and most critical stage in performing several common molecular techniques including reverse transcription real-time PCR (RT-qPCR), digital droplet PCR and cDNA library construction. The process of RNA extraction broadly involves the following steps:

1. Sample Preparation: The initial preparation steps differ depending on the source that the RNA is to be extracted from. For example, if RNA is to be extracted from bone samples, then the lytic agent or denaturant may not make contact with the cellular contents at the moment the cells are disrupted. Therefore, these samples may require freezing before starting the extraction process.
2. RNA preparation: Several RNA preparation methods can be used which can be summarized into 4 general techniques
   1. Organic extraction methods: Often considered the “gold standard” for RNA preparation
   1. Filter-based, Spin basket formats: Which utilize membranes that cell lysate pass through, allowing for the isolation of nucleic acids containing RNA.
   1. Using Magnetic Particles: Magnetic particles bind to RNA due to surface modifications on the particles which are then collected using an external magnetic field and easily removed and washed
   1. Direct lysis methods: Using lysis buffers, cell or tissue samples are disrupted and release cellular contents before being purified.
3. Quantification of Isolated RNA: RNA that has been isolated from cells undergoes further purification and quantified using UV spectroscopy, fluorescent dyes  or instruments that employ a combination of microfluidics, capillary electrophoresis and fluorescent dyes to evaluate RNA concentration levels.
4. RNA Purification and storage: Finally, the isolated RNA is purified to remove any impurities such as proteins or residual DNA that could interfere with downstream applications. After purification the RNA is suspended as a purified RNA pellet and stored for future use or used immediately.

RNA extraction must be performed carefully to minimize RNA degradation, which can occur due to endogenous RNases, mechanical or chemical damage, or improper storage. RNA extraction protocols may vary depending on the sample type and the downstream applications, and there are several commercially available RNA extraction technologies that can simplify the process and improve RNA yield and purity. One of these used by Sampled is the PAXgene® Blood RNA Tube which is designed for stabilization of intracellular RNA, supporting robust processes further downstream with a higher level of reproducibility.

Why Outsource RNA Extraction?

1. Expertise – Processes performed by experts with extensive experience in RNA extraction protocols. Sampled Labs feature state-of-the-art facilities, technology, and capabilities, which can lead to higher-quality RNA yields and fewer technical errors.
2. Turnaround Times – Outsourcing could save time and reduce costs compared to performing the process in-house. E.g., Sampled could be able to offer a faster turnaround time and have a higher capacity to handle larger sample volumes, resulting in faster and more cost-effective RNA extraction.
3. Scalability – Sampled can flexibility and scalability, allowing researchers to focus on the analysis while leaving the RNA extraction to us. Sampled are also able to offer customized solutions to meet specific research needs or aims.

RNA extraction is a crucial process in molecular biology, genetics, and medicine. It plays a vital role in gene expression analysis, disease diagnosis, drug discovery and forensics. Constant developments from technology providers and researchers, RNA extraction will remain an essential tool for researchers and clinicians in the years to come.