Tissue Procurement Problems


Formalin-fixed paraffin embedded (FFPE) tissue blocks are a valuable resource for many significant research programs as researchers tend to select this type of biospecimen as frozen or fresh tissue blocks may be harder to acquire. There is also the challenge that the number of fresh frozen tissue samples may not be able to fulfill the requirements of the research protocol. The FFPE preservation technique demands a fast and rapid fixation after the process of resection of the target biospecimen in a neutral buffered formalin. Once fixed, the specimen is then embedded in paraffin wax. FFPE is now the commonest tissue preparation method used to archive research biospecimens. Currently, almost all surgeries in this day generate FFPE tissue samples. FFPE tissue blocks are crucial as they offer the potential for the discovery of significant information especially in biomedical research programs and drug discovery. Other research applications that utilize FFPE biospecimens include:

  • genetic studies
  • biomedical identification or authentication
  • visualization of tissue structure

This, therefore, makes FFPE tissue blocks ideal for:

  • the study of autoimmune diseases – rheumatoid arthritis, systemic lupus erythematosus
  • the study of long-term cancers – colon cancer, lung cancer, breast cancer



However, there are several challenges that researchers face when it comes to obtaining FFPE tissue samples. Some of the challenges include:


1)     Oversight of the Pathologist

In some cases, the FFPE samples are not obtained or processed appropriately as the certified pathologist is not on site to supervise and ensure that the proper procedures are followed during the procurement of the specimen. Biorepositories should ensure that they hire enough licensed pathologists to ensure that there is no manpower shortage as it could impact the quality of their tissue specimens.


2)     Difficulty Acquiring Samples

There are certain situations where a research team or company requires access to FFPE tissue samples that are hard to come by. For example, FFPE samples from patients with metastatic melanoma might present a challenge to biorepositories. Research teams should partner with a biorepository that has a vast network for tissue procurement as it can help tremendously in the collection of special samples needed in specific research protocols.


3)     Rapid Turnaround

Studies or research that needs a quick procurement of FFPE tissue blocks may pose a challenge to many biorepositories. These research teams that are looking for a rapid turnaround of samples should ask biorepositories about their accelerated procurement method which may then be able to provide the required biospecimens within the time frame.


4)     Transparency

Research teams looking to procure tissue samples need to keep in mind about transparency as studies rely on well-annotated tissue blocks that go through the proper fixation and preservation technique. Before obtaining samples from the biorepository, be sure to ask regarding their specifics and standard of procedure for the fixation and quality assurance protocols. This can impact the result and credibility of the entire study.


5)     Review of FFPE Biospecimens

Some biorepositories obtain their tissue samples from local sources such as the local hospitals. However, not all providers take the time to ensure that the specimens are of the highest quality. Biorepositories are responsible to ensure that a gross and microscopic examination of the FFPE biospecimens to ensure that the samples obtained are of the highest quality.


6)     Sourcing

With the growing number of organizations and biorepositories, research teams that are looking to source biospecimens should consider companies that follow the best practices and have high standards when it comes to their collection and fixation protocols. Unreliable sources may not be able to provide high-quality FFPE tissue samples. Before procuring the required biospecimens, enquire where the organization obtains their samples and the reliability of it.


7)     Patient Information

The patient information from the samples can be valuable and crucial in a research. The more information you can obtain regarding the patient from their data, it can help with some of the results from the research especially in terms of demographics and risk factors of a disease. Patient information also helps you to find the correct patient cohort as some study designs exclude those below or above a certain age. It is therefore important to procure the biospecimens from a biorepository that can provide the necessary data such as the details or a refractory disease, metastatic diseases, or newly diagnosed disease. A new case of cancer or a relapse can also affect the results of a study greatly.



In conclusion, there are many factors to consider when it comes to selecting a new biorepository or organization to partner with to obtain tissue samples. It is important as these specimens ultimately determine the results and credibility of the study. Choosing a credible company that provides the highest quality FFPE tissue samples is one of the most crucial steps in the early stages of a study. Low-quality biospecimens result in wasted hours of study, effort, and decreases the overall morale of the research team.



Doiron L. Typical problems with FFPE tissue samples – and how to solve them. 2014. Folio Conversant. Accessed 7/11/2018. 


Tissue Microarray


The recent advances that have occurred in the human molecular genetics field have found that there are gene-based disease mechanisms in various areas of medicine. Studies regarding diagnostic and prognostic markers in many clinical specimens is vital in the translation of new findings from basic science to applications in clinical practice. With the increased use and advancements of new molecular biology methods, the research of progression and pathogenesis of diseases such as cancer are now revolutionized. Understanding the basic molecular mechanisms in the progression of normal tissues to cancerous or malignant tumors is crucial in the knowledge of the disease as it can lead to improved treatment, diagnosis, and cures. Some clinical studies have discovered various novel markers at the gene level where validation of these markers is necessary. However, it can be a time consuming, costly, and labor-intensive process especially if tested on several specimens.


Tissue Microarray

Tissue microarray is a method used in the field of pathology to overcome issues where the validation of markers is:

  • Time-consuming
  • Costly
  • Labor-intensive

It can be used to organize small amounts of tissue samples on a solid support. It is a method designed to allow the:

  • Simultaneous assessment of gene expression on hundreds on tissue samples
  • Parallel molecular profiling of tissue samples at DNA, RNA, and protein level
  • Analysis of samples using fluorescence in situ hybridization (FISH), immunohistochemistry, and RNA in situ hybridization at lower costs and less time


Tissue Microarray Construction

Tissue microarrays can be constructed using composite paraffin blocks through the extraction of cylindrical core biopsies from donor blocks which are them embedded into a microarray or recipient block at specific array coordinates. Donor blocks are first retrieved and sectioned to produce the standard slides. These slides are then stained with hematoxylin and eosin. Once ready, the slides are examined by a certified pathologist who then marks the area of interest (usually an area with pathology such as cancer). Next, the samples can be arrayed. A tissue core can be acquired from the donor block using a tissue microarray instrument. This tissue core is then inserted into an empty recipient or paraffin block at a specific coordinate which is recorded on a spreadsheet. The sampling process is then repeated as many times as necessary from various donor blocks until many cores are placed in one recipient block. This results in the final tissue microarray block. A microtome is utilized to cut 5-micrometer sections from the blocks to produce slides necessary for immunohistochemical and molecular analyses.


Applications and Advantages

Tissue microarrays have many advantages over other techniques. Some of it include:

  1. Amplification of a scarce resource – After a standard histological section that is approximately 3 to 5 millimeters thick is used in primary diagnosis, the sections can further be cut 50 to 100 times yielding a total of 100 assays. In tissue microarrays, instead of 50 to 100 samples, it can produce material enough for 500,000 assays.
  2. Simultaneous analysis – Tissue microarrays allows the simultaneous analysis of many specimens as it provides high throughput data acquisition.
  3. Uniformity – In tissue microarrays, every tissue sample is treated uniformly. It can also be used in a variety of techniques such as fluorescent or chromogenic visualization, histochemical stains, tissue microdissection techniques, and more. Tissue microarray enables the analysis of the entire cohort on one slide standardizing the variables such as incubation times, antigen retrieval, washing procedure, reagent concentration, and temperature.
  4. Time and cost efficient – The tissue microarray method require small amounts of reagents for analysis. It is a method that is both time and cost efficient.
  5. Conservation of tissue samples – Tissue microarray is a technique that does not destroy the original block of the tissue sample.


Tissue Microarrays from Fresh Frozen Tissue

In tissue microarray, the method uses tissue samples from paraffin-embedded tissue donor blocks that are then placed into a recipient block. One of the challenges with paraffin-embedded tissue is the antigenic changes seen in proteins and degradation of mRNA due to the fixation and embedding process. Some researchers have modified the tissue microarray technique by using fresh frozen tissue that is embedded in optimal cutting temperature (OCT) compound. It is then arrayed into a recipient OCT block. Tissue samples are not fixed before the embedding process and the arrayed sections are assessed without fixation. The advantage of tissue microarrays from fresh frozen tissue is that:

  • It works well for DNA, RNA, and protein analyses.
  • Paraffin-embedded tissue arrays can be challenging for RNA in situ hybridization and immunohistochemistry analyses but tissue microarrays from fresh frozen tissue allow the optimal assessment by each technique.
  • It has uniform fixation throughout the whole array panel.
  • It is a technique that may have significant advantages in the assessment of certain genes and proteins as it improves both quantitative and qualitative results.



1)      Jawhar NMT. Tissue microarray: a rapidly evolving diagnostic and research tool. Ann Saudi Med. 2009; 29(2): 123-127.

2)      Fezjo MS, Slamon DJ. Tissue microarrays from frozen tissues – OCT technique. Methods Mol Biol. 2010; 664: 73-80.


FFPE Samples

What is Formalin Fixed Paraffin Embedded Tissue?

Formalin fixed paraffin embedded or FFPE tissues are valuable for both therapeutic applications and research. FFPE is a specific technique used to prepare and preserve tissue specimens utilized in research, examination, diagnostics, and drug development. Tissues are first collected from both diseased and non-diseased donors. The tissue specimen is first preserved through a process called formalin fixing. This step helps to preserve the vital structures and protein within the tissue. It is then embedded into a paraffin wax block and sliced into the required slices, mounted on a microscopic slide, and examined.


The FFPE Process

The process starts by a specimen being selected and then excised from a donor or patient. Samples can also be obtained from other animals such as snakes, mice, or many others. After excision, the tissue is immersed for approximately eighteen to twenty-four hours in a 10% neutral buffered formalin. The tissue is then dehydrated using increasing concentrates of ethanol. Next, the tissue is embedded into paraffin to become FFPE blocks. The methods utilized are dependent on the requirements of the researcher or physician who is requesting the FFPE samples. Specifications about how the issue is cut, size, and purpose of the tissue are all important. Once the procedure is complete a certified pathologist will  evaluate the quality of the specimen.


Storage of FFPE Tissue

FFPE samples can be stored in hospitals, biobanks, and research centers. Storage facilities often keep records of how the tissue was collected, the preservation procedures, and demographic information (such as, but not limited too: the origin, duration, age, ethnicity, gender, and stage of disease) of the donor. The demographic information is an important factor in research and in clinical trials. FFPE samples that are properly preserved are very valuable and can be stored at room temperature for a long period of time.



FFPE samples are important as they are often used in:

a)       Immunohistochemistry

The sectioned FFPE specimens are mounted on a slide, bathed in a solution containing antibodies, and then stained so that they can be more clearly seen. This method is important for physicians and researchers looking for pathology in the tissue such as Alzheimer’s or cancer.

b)      Oncology

FFPE samples are vital in the field of oncology as tumor tissues have characteristic morphologies allowing researchers to look for certain proteins. These proteins are then used to help in the assessment of treatment and diagnosis.

c)       Hematology

In the study of blood and its disorders, FFPE samples are important in determining the anomalies and discovery of cures. The specimens can be used in studies related to tissue regeneration, genetics, and toxicology.

d)      Immunology

FFPE samples from a donor with autoimmune disease helps in determining the cause and development of therapy for the condition.


Complications or Limitations

One of the possible limitations of the fixation process using formalin is the potential denaturation of the proteins that are present in the tissue making them undetectable to antibodies. To compensate for this issue, antigen retrieval techniques were developed. The antigen retrieval technique specifically recovers DNA, RNA, and proteins from FFPE samples. For this method to work, the quality of FFPE samples are critical. There is also the issue that there is no standard procedure to be used in the preanalytical processing such as fixation and DNA isolation. This means that minor differences such as the different use of instruments, sample handling, and methodology can result in variation that affects the quality of DNA and study results. Some of the factors that have been found to affect study results from FFPE samples are:

  1. Inaccurate logging of fixation protocol
  2. Variation in fixation time
  3. Temperature during fixation
  4. Storage conditions of FFPE samples


Quality Control

To ensure the highest quality of FFPE samples, those who collect and store these samples should:

  1. Follow ethical and legal standards.
  2. Keep a clear and accurate record of donors.
  3. Provide information regarding the sampling and collection process
  4. Be supervised by a licensed pathologist during the collection of samples
  5. Have a complete chain of custody
  6. Work only with a carefully selected network of distributors that consistently provide high quality and accurate samples

Fresh Frozen Tissue

Fresh frozen tissues are specimens that are preserved using liquid nitrogen through a method known as “flash freezing”. These specimens are then stored in a freezer that is set at a temperature of less than -80 degrees Celsius. Fresh frozen tissue has different applications than  FFPE samples as they can be used in native morphology studies or molecular analysis as well.


FFPE Samples Vs. Fresh Frozen Tissue

FFPE and fresh frozen tissue have their pros and cons. They are two different types of samples that have different uses dependent on the requirements of the research or clinical study. 

  1. FFPE blocks are very hard and can be easily stored at room temperature for decades without the need of special equipment making the type of tissue sample very cost efficient.
  2. There is a large archive of FFPE samples available for researchers due to the easiness associated with it storage.
  3. FFPE specimens have been used for decades making it incredibly familiar to pathologists.
  4. Fresh frozen tissue is much more suitable for the analysis of native proteins, polymerase chain reaction, and next generation DNA sequencing.
  5. Fresh frozen tissue ensures the preservation of DNA, RNA, and native proteins.
  6. Fresh frozen tissues require specialized equipment for storage. This means mechanical failure, power outages, and carelessness can affect the quality of the samples.



1)      FFPE tissue samples / quality control. Horizon. Accessed 6/19/2018. https://www.horizondiscovery.com/reference-standards/our-formats/ffpe/ffpe-tissue-samples-quality-control4

2)      Ward T. The importance of proper formalin fixation of FFPE samples. Personalis. Accessed 6/19/2018. https://www.personalis.com/importance-proper-formalin-fixation-ffpe-specimens/

3)      Doiron L. 5 quality control rules for cancer tissue banks. Folio Conversant. Accessed 6/19/2018. http://www.conversantbio.com/blog/bid/339034/5-Quality-Control-Rules-for-Cancer-Tissue-Banks

4)      FFPE vs frozen tissue samples. BioChain. Accessed 6/19/2018. https://www.biochain.com/general/ffpe-vs-frozen-tissue-samples/

5)      What is FFPE tissue and what are its uses. BioChain. Accessed 6/19/2018. https://www.biochain.com/general/what-is-ffpe-tissue/


Cancer Therapy

Thanks to extended research from human tissue samples we have been able to make major breakthroughs in cancer research. In the twenty-first century, evidence, both epidemiologically and clinically, have supported that the changes in whole-body metabolism can affect oncogenesis, the progression of tumors, and the response of tumor to therapy. It has been observed that metabolic conditions such as hyperglycemia, obesity, hyperlipidemia, and insulin resistance are associated higher with risk of cancer development, accelerated progression of tumors, and poor clinical outcome. Due to these findings, many clinical studies indicate that statins and metformin may help in decreasing cancer-related mortality and morbidity. Phenformin is another drug used to treat diabetics that can help with anticancer effects. However, phenformin was discontinued in the late 1970s due to a high incidence of lactic acidosis. Metformin is the most commonly used antihyperglycemic agent globally. It has an optimal pharmacokinetic profile with:

·         50 – 60% of absolute oral bioavailability

·         Slow absorption

·         Negligible binding to plasma protein

·         Broad tissue distribution

·         No hepatic metabolism

·         Limited drug interactions

·         Rapid urinary interaction

It also has an exceptional safety profile as there is a low number of individuals who have side effects. Statins also have a great safety profile and is currently used by a large population.

Cancer and Cellular Metabolism

The accumulation of evidence has suggested that malignant transformation is linked to changes that affect several factors of metabolism. Metabolic rearrangements associated with cancer have been linked with the inactivation of tumor suppressor genes and activation of proto-oncogenes. However, the accumulation of metabolites such as fumarate, succinate, and 2-hydroxyglutarate (2-HG) drives oncogenesis through the signal transduction cascades. Conclusively, these observations support the notion that signal transduction and intermediate metabolism are associated.


a)       Oncogenes and Metabolism

The signaling pathways from oncogenic drivers are linked to metabolic alterations due to cancer. For example, the expression of the PKM2 (an M2 isoform of pyruvate kinase) encourages the alteration of glycolytic intermediates in the direction of anabolic metabolism while regulating both transcriptional and post-transcriptional program that leads to the addiction of glutamine.


b)      Oncosuppressors and Metabolism

There are some oncosuppressor proteins that can regulate cellular metabolism. The inactivation of tumor suppressor p53 happens in more than 50% of all neoplasms causes a variety of metabolic consequences that could potentially stimulate the Warburg effect. P53 can possibly suppress the transcription of GLUT4 and GLUT1 and stimulate the expression of apoptosis regulator (TIGAR), TP53 induced glycolysis, SCO2, glutaminase 2 (GLS2) and many other pro-autophagic factors. It also interacts physically with glucose-6-phosphate-dehydrogenase (G6PD) with RB1-inducible coiled-coil 1 (RB1CC1).

c)       Oncometabolites and Oncoenzymes

It was found that metabolites can contribute to oncogenesis when mutations such as fumarate hydratase (FH) and succinate dehydrogenase (SDH) was linked to sporadic and familial types of cancer including pheochromocytoma, leiomyoma, renal cell carcinoma, and paraganglioma. once the enzymatic activity of SDH and FH is disrupted, succinate and fumarate accumulate resulting in oncogenesis.

Targeting Cancer Metabolism

The metabolic targets for cancer therapy rewiring of cancer cells is seen as a promising source for new drug targets. Some different approaches have resulted in the identification of agents that can help with targeting glucose metabolism for cancer therapy. However, the low number of metabolic inhibitors reflect the recent rediscovery of the field. There are also some concerns about the uniformity between malignant cells and non-transformed cells that are undergoing proliferation.


a)       Targeting Bioenergetic Metabolism

Some cancer-associated alterations such as the Krebs cycle, glycolysis, glutaminolysis, mitochondrial respiration, and fatty acid oxidation have been studied as potential sites for drug therapy.


b)      Targeting Anabolic Metabolism

The anabolic metabolism in cancer cells increases the output from nucleotide, protein, and protein biosynthesis pathways to help with the generation of new biomass in rapidly proliferating cells (includes both normal and malignant). A high metabolic flux through the pentose phosphate pathway is vital to cancer cells as it generates ribose-5-phosphate and nicotinamide adenine dinucleotide phosphate (NADPH).


c)       Targeting Other Metabolic Pathways

Other pathways involved in the adaptation to metabolic stress may provide drug targets for cancer therapy. This applies to autophagy, hypoxia-inducible factors 1, and nicotinamide adenine dinucleotide metabolism. A competitor of nicotinamide phosphoribosyltransferase (NAMPT) known as FK866 has been observed to have antineoplastic effects in murine tumor models.



The extensive metabolic rewiring in malignant cells provides a large number of possible drug targets. Many agents that target metabolic enzymes are used for decades while others are being developed. Therefore, the use of metabolic modulators that could be complicated by the similarities of highly proliferating normal cells and metabolism of malignant cells, there might be a chance to harness the antineoplastic activity of these drugs clinically. While many efforts were focused on merging metabolic modulators and targeted anticancer drugs, there may be a common view that metabolism and signal transduction are mostly independent if not separate entities. More research is needed to study the extent of how the metabolic functions of oncosuppressive and oncogenic systems contribute to the biological activity.


Galluzzi L, Kepp O, Vander Heiden MG, Kroemer G. Metabolic targets for cancer therapy. Nature Reviews Drug Discovery. 2013; 12: 829-846.

The importance of Biorepositories

Biobanks & Biorepositories

A biorepository is a storage facility for biological materials that includes animal and human tissue samples. A biobank is similar but it is not the same thing as a biorepository. A bio bank is a collection of similar types of samples, that are grouped together based on population, disease type etc. A biobank collects, stores, and processes bio specimens for use in both research and clinical studies. There are countless parties involved in the successful operation of a biorepository like, Geneticist Inc.. a strong support system is required for one to function, these can include, but are not limited to, patients, regulators, investors, governments, healthcare workers etc.

A biobank functions as a biorepository that gathers, processes, stores, and provides specimens and data that is used in research and clinical studies. The biobanking field has changed greatly over the last three decades starting with a small university-based repository developed for the needs of particular projects. It then gradually evolved to include institutional repositories, government repositories, commercial repositories, population biobanks, and virtual biobanks. The data gathered provides information that demonstrates participant or patient phenotype which extends in both genetics and proteomics. Population-wide biobanks have been developed in many countries globally to collect, analyze, and store information that represents samples of their population source. As for virtual biobanks, they function using a special software or web portals that help to connect biobanks and investigators globally.

Biobanking: Responsibilities and Benefits

Biobanking is a process where tissues (both plants and animal) and bodily fluids are collected as samples for the purpose of research to improve the understanding of disease and health. Information that may affect the sample such as height, weight, lifestyle, and family history will also be recorded to provide some background information for the samples. The collected samples can be kept indefinitely or over a period of several years depending on the type of research. Researchers will then track the health of study participants by observing and recording their past, present, and future medical records if they have consent. There are specific biobank projects that specialize in specific conditions. While this may be the case, both healthy volunteers and individuals with the condition will be required for the participation of the study. Samples that are collected for a specific research can also be kept for future use in other research. In genetic conditions, family members of participants can also be recruited to compare their medical history to others who also suffer from the same condition.

Informed Consent

Before participants agree to participate in biobanking, they are usually informed in writing about what to expect and should understand that they can always refuse to be involved further if they feel uncomfortable at some point during the research. The data, information, and samples gathered can be shared with other scientists and researchers such as those in universities, private institutes, or government institutes in other parts of the world. However, it is made clear that samples collected cannot be sold for profit. The sharing of information allows research to be conducted on a larger scale leading to a better understanding of health, advancements, and faster development of new treatments.

Legal and ethical issues

Despite government and institutional involvement in biobanks there has been a lot of legal and ethical gray area attributed to bio banking. External regulatory pressure has led the industry to take much greater care in the execution of their collection and storage. One of the biggest issues that faces the industry, despite laws varying from country to country, is that donors are not getting financially rewarded even though their body parts are being sold for thousands of dollars.        

History of Bio banks

Biobanks have been around in one form or another for over a century. Back then they were shells of what they have become today. Similar to today’s biobanks they too were hosted at universities where scientists tend to conjugate. They were small and developed with specific research and studies in mind. Interestingly enough, mentions of histology have been found in literature as early as 1817. As time has passed and as the importance of biobanks has become more widely understood and appreciated they have grown to become much larger. Eventually governments and institutions alike have become involved and we now even have population wide biobanks.


In the field of biorepository, it has evolved according to the changing needs of investigators and studies that utilize specimen banking while adhering to regulatory and related guidelines and pressures. The changing environment can be attributed to fields such as genomics, proteomics, and personalized medicine that increases the precision of science. It has increased the demand for high-quality specimens that are reliable, accurate, and has standardized laboratory and clinical data. This is why the process of collection, storage, tracking, and shipment are vital to the outcome of studies. Regulatory requirements such as the Health Insurance Portability and Accountability Act (HIPAA), and Institutional Review Board (IRB)have been developed to address consent, ethical, and legal issues.

Evolution of the Biobank and its Diverse Activities

In the United States, specimens have been collected and stored for more than a century. Banks have expanded their activities from small operations based on small studies to become a much more complex enterprise. Advances such as procedure automation and computerization have transformed the management of these biobanks. Specimens can now be logged onto a computerized database. Biobanks with sufficient funding can now invest in robotics to accelerate processing and sampling. The internet has enabled communication with clients and companies now exist to support biobanks in terms of inventory tracking, consent documentation, and handling of laboratory and clinical data. Robotic devices can handle specimen processing and national biorepositories have made it possible to study large populations throughout the entire lifespan. For example:

  1. UK Biobank – Created after 10 years of planning aiming to improve prevention, diagnosis, and treatment of life-threatening illnesses. They have reported a recruitment of half a million participants between the ages of 40 to 69 during 2006 to 2010.
  2. The University of California, San Francisco AIDS Specimen Bank (ASB) – Started in 1982 as a response to the challenges of AIDS epidemic.
  3. National Cancer Institute announced the establishment of US National Cancer Human Biobank (caHUB) – Created due to concerning needs for human biospecimens and aims to improve and modernize the field of biobanking through standard operating procedures and standards.
  4. Virtual biobank -  Created as an electronic database that contains information of biological specimens regardless where the specimens are stored. There is one in University College London Virtual Biobank that collects information of existing and new biospecimens. It will eventually become a data repository for all health science centers. Its founders are currently attempting to develop a software system that houses sample and phenotype data, so all researchers can view information on all collections.

Virtual biobanks are the future of bio banking. Technological advances in AI software and robotics is changing the way we manage and operate biobanks. The most modern of biobanks are using computerized databases of specimens accessible by a google-like search engine. Software companies have developed tracking, processing and documentation systems specific to the bio banking business. The future of bio banking looks very bright, so long that standard operating procedures are abided by.



1)     Biobanking. Healthtalk. Accessed 5/30/2018. http://www.healthtalk.org/peoples-experiences/medical-research/biobanking/what-biobanking-and-why-it-important

2)     De Souza YG, Greenspan JS. Biobanking past, present, future: responsibilities and benefits. AIDS. 2013; 27(3): 303-312.