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Biosample Research Guide

Sampled serves our scientific community with tremendous pride. Biosample research science is growing exponentially in countless ways, including the applications of cell and gene therapy, mainly because of the monumental gains in the field of biotechnology and molecular science. As such, biosample research is an integral component in developing new treatment solutions and novel drug discoveries.

The lifecycle of the “biosample” includes intricate sample management practices, informatics, molecular science, stem cell research, tissue pathology, and much more. We invite you to learn more about Sampled and our suite of services as we guide you through the exciting industry of biosample research.

Common Types of Biosample Research

The major types of biosamples used in clinical and basic research include:

• Plasma
• Primary Cells and Cell LInes
• Bone Marrow
• Solid tissues (tumors and normal)
• Blood
• Saliva
• Urine
• Stools

The biosample “type” is typically assigned a taxonomic designation for submission purposes. The NIH maintains a database containing taxonomy details and attributes to be used by researchers when completing regulatory documents.

Stem Cell Research

Decades of research into the mechanisms governing the development of cells have led to the discovery of the earliest progenitor cells from which most other cell types arise in the body. The discovery of these “stem”cells has opened up the potential of a new area of therapy called regenerative medicine.  Regenerative medicine is based on the use of stem cells, either isolated as naturally occurring cells from a person or derived by reprogramming their own differentiated cells, to replenish cells that are lost or damaged due to a disease such as Parkinson’s, to name one example.  Clinical studies using embryonic and adult stem cells demonstrate significant potential in treating difficult health conditions.

Cellular Services

Cellular research services are a trending topic in biotechnology and have had an extraordinary impact in the areas of genomics, proteomics, regulatory changes, and the clinical market. To date, more than 20,552 biotech companies are in operation worldwide offering a broad range of cellular-based science services.

Cellular service offerings are demonstrated in almost every life-science sector. Biotech product services include: tissue processing to isolate primary cells such as peripheral blood mononuclear cells (PBMCs) from the blood, large-molecule proteins; monoclonal antibodies; stem cells, peptides, liposomes, reagents, polymers, and molecularly engineered vaccines and therapeutics.

Cell Line Establishment

Cell lines play key roles in basic research and preclinical studies conducted by pharmaceutical and biotech companies. Cell line establishment provides tools used in testing for drug efficacy, metabolism and cytotoxicity. Cell lines are also necessary for vaccine and antibody production. Cell lines derived from pluripotent stem and embryonic stem cells are used in many advanced applications such as the generation of artificial tissues and therapeutic proteins.

Tissue Pathology

Tissue pathology, sometimes referred to as histopathology, describes the comprehensive biological analysis of tissues associated with a specific disease state. In most cases, the tissues have been surgically removed from the body for diagnostic and/or therapeutic purposes. [3]. The analysis is conducted by trained pathologists and technical staff with the goal of identifying abnormal cells or structures that can then inform research or clinical classification, providing the clinician with tools to aid in making diagnostic and therapeutic decisions.

Genetic Mapping

Gene mapping, sometimes referred to as linkage mapping, describes the methods used to identify the locus of a gene and also the distances between genes. For example, gene mapping offers valuable information regarding the chances for parent-to-child disease transmission. Gene mapping also provides some clues about the chromosomal location of th gene.

Gene Sequencing and Genome Assembly

Genomic sequencing is an important tool in genetic research used to determine the unique sequence contained in a DNA strand. In essence, gene sequencing details the genetic makeup for any living organism. Every living organism hosts a sequence of nucleotides, (adenine, guanine, cytosine, and thymine), in a unique order contained within the DNA molecule. Genomic sequencing and assembly are also tools used to identify genetic biomarkers in personal DNA kits such as 23 and Me.[3] Recent technical advances in genomic sequencing, enabling the sequencing and analysis of the entire genome of an individual in a relatively rapid and economical manner, have led to leaps in our ability to determine the genetic causes for many diseases as well as diagnose diseases with greater accuracy and speed than was previously possible.

DNA Fingerprinting

DNA fingerprinting is a laboratory method used to analyze nucleotide patterns contained in DNA samples for identification purposes. It generally used to assign paternity or to link a suspect to a criminal investigation. Biorepositories use DNA fingerprinting to validate the identity of subject

Clinical Research and Biorepository Services

The scale of scientific research programs has grown exponentially over the years, as technological advances enable us to ask questions about the human condition was were previously unattainable. Asking such questions requires coordination among many scientists around the globe. These “Big Science” projects involve a large scale in terms of numbers of samples, often in the thousands, and instrumentation, costing millions of dollars. Biorepositories play a vital role infacilitating this “big science” approach. . Not only do have the capability of processing and storing millions of samples, investing in the sophisticated instruments necessary to analyze them,, but they also act as partners in many clinical and research studies. Biospecimen quality is paramount. Biorepositories must meet stringent clinical and research regulations in addition to addressing client needs with regards to customizations, scale, and the ability to provide a safe infrastructure.

Research, Experiment, and Clinical Study Design

Medical research is performed by scientists specializing in specific fields such as genomics, molecular chemistry, and others. Using animal models, they apply their unique skillsets to help answer questions related to many cellular-based interactions such as the relationship between DNA and mRNA, biological function and influence, and the mechanism of action (MOA). Clinical research is the action of taking the laboratory solutions and testing them in human clinical trials. Together, they work congruently to develop new treatment solutions.

Before the clinical trial is initiated, a clinical research associate (CRA), or coordinator (CRO), creates a study design that is best suited to the testing parameters. Planning a study takes a great deal of time and organization. Clinical studies are free and participation is on a volunteer basis. Diverse recruitment for clinical studies are crucial to help determine the true efficacy of a therapeutic product.

There are two types of clinical study designs:

Observational study designs are designed to generate a hypothesis. They address the: what, who, where and when questions include a large degree of reporting.

Experimental study designs seek to determine if a therapeutic intervention is effective that have control groups built into the study. They are looking for any pharmacokinetic details that may render the intervention unsafe or ineffective.

Biosample Collection, Processing, Management, and Storage

Biorepositories maintain a diligent set of best practices related to all facets of biosample management such as the ISBER best practices. This encompasses biosample collection, processing, management, and storage functions. The scope of work performed by biorepository scientists is intensely regulated. As such, Sampled maintains  accreditations recognized by the global scientific community: CAP (College of American Pathologists), CLIA (Clinical Laboratory Improvement Amendments), which validates the quality of its practices

Our facility is an internationally accredited entity which lends a high degree of credibility to what we do here at Sampled. Our processes are unique and proprietary and truly puts in a different category and we also have a superior track record of success in our methodologies. – Dana Garbolino, Senior Director of Communications and Project Management.

Many of the processes employed by Sampled are automated and proprietary to our facility. These state of the art processes streamline biosample handling from beginning-to end. Automation is shown to minimize human-error and optimize the quality and efficient use of precious biosamples. Clinical studies state that human error is the largest contributor to biosample waste and contamination.

Biosample storage is determined by sample type and allows for customizations by the client. There are several types of biosample storage options. Storage conditions vary and include broad temperature ranges including LN2 or cryopreservation. {back link to previous storage pieces}.

Clinical Validation

Simply stated, clinical validation is a formal review of a case to examine if the patient’s reported condition is accurate. The process for clinical validation includes examining the clinical indicators to ensure they correspond correctly to the assigned diagnosis.

Regulatory Submission Report

There are two main branches of submission documents that encompass laws and regulatory guidance which have to be filed with the FDA:

Investigational New Drug Applications (IND)

The initial IND is the first step of the regulatory submission process that allows a drug company to proceed to the clinical research phase. The IND process is ongoing and is often amended many times throughout the drug’s lifespan in the clinical marketplace.

New Drug Applications (NDA)

The NDA is a regulatory formal process to introduce a new drug into the clinical market space for sale and marketing. These applications contain clinical and non-clinical study reports, manufacturing information, and administrative reports.

Regulatory submission reports are designed for the sole purpose of offering proof of compliance for both new and existing drugs. Regulatory submissions typically begin during preclinical phase of drug development and continue throughout the clinical trial phases.

Regulatory submission reports contain a large volume of information regarding the entire scope of the referenced drug. They are typically quite comprehensive and require a lot of focus and time to complete. It is not uncommon for some regulatory reports to exceed thousands of pages of meticulously documented information related to the drug’s pharmacokinetic properties and manufacturing process.

Bioinformatic Research Solutions

Bioinformatics is an important tool which enables you to identify, evaluate, store, and retrieve biological information. Bioinformaticians integrate biological data and statistics to develop dynamic research applications.

We pair robust bioinformatics and state of the art automation here at Sampled. Our facility operates at proficient level at every functional point – many of which intersect. – Chirayu Goswami, Senior Director of Informatics.

The applications provide research solutions by analyzing DNA sequences, protein analysis, and molecular activity. The analysis of these large and complex datasets requires an analytical platform capable of handling expansive applications.

Understanding Biological Data in Large Sets

Biotechnology accumulates large volumes of information of biodata. Researchers use the information to validate their research relative to disease subtypes and/or conditions. 

Large data sets or big data, are categorized into these four subsets:

• volume of data
• velocity of processing the data
• variability of data sources
• veracity of the data quality

Custom Data Formatting

Biorepostiory science has undergone dramatic changes within the last decade. Biorepositories use and develop software to apply bioinformatics that link directly with Laboratory Information Management Systems (LIMS). LIMS are sophisticated databases that track millions of biosamples, maintaining critical information about their biology and clinical history. . This allows researchers to analyze data from large sets of samples and make important discoveries about the origin and progression of human diseases..

The function of this information is facilitated by the use of custom data formatting which entails how data is expressed. Large amount of information is filtered through custom field generation i.e. data models, classification, etc. This helps create not only a high-degree of organization for the originator, but also simplifies the process for the interpreter.

Data Computation and Analysis

Biorepositories generate a significant amount of bioinformatic data. Organizing large amounts of data requires skilled bioinformaticians who know how to apply mathematical and statistical applications. This is a major element new to the scientific landscape that helps decipher big data loads. The information is then capable of generating a myriad of analytical reports relevant to any clinical-based projects.

Computer Science and Statistical Techniques

Statistical techniques are used to help give clarity and insights about biodata and assess the significance of associations withing the data. Common statistical methodologies include:

Mean

This method works to determine the trend of the referenced data set. It is known for providing a clear concise view of big data sets. However, it is not recommended as a standalone method.

Standard deviation

This measures the spread of data around the mean and works best in clustered data sets.

Regression

This method details the relationship between a dependent variable and independent variable.

Hypothesis testing

Commonly referenced as “T” testing, this method analyzes random variables within a data set.

Sample size determination

In some cases, the dataset is too large to collect accurate data for each element of the dataset. When this happens, analyzing a sample size, or smaller size, of data, is a better option and referred to as sample size determination.

Quality Control Assays

Quality control assays are used as tools to maintain constant vigilance over all the work that is performed in a biorepository, ensuring that precious samples are  processed, stored and distributed with the highest possible standards of quality and sample integrity. This is accomplished by including controlled specimens into the testing process and exposing them to specific conditions to determine any faulty operation.

Scalable Biosample Research with Sampled

Sampled is a full service biorepository that can scale your project from start to finish. We specialize and provide consulting services for experimental design, platform and technology selection, as well as bioinformatics support and data analysis.

We also offer comprehensive services for next-generation sequencing on the latest platforms from Thermofisher, Illumina and Pacific Biosciences, to name a few. Service bundles include nucleic acid extraction, integrated sample QC, sample processing and fully automated construction of sequencing libraries.

We meticulously evaluate each project and create a customized, comprehensive plan for sample size, sample collection, consent strategy, sample storage volumes/environments, and sample bioprocessing technologies in order to maximize downstream capabilities.

The integration of collection kit manufacturing, sample collection and transport are among the most critical components of any study. Sampled has an extensive logistics framework in place that has been validated in over 300 studies to date. Every study has specific requirements that can be addressed in the study logistic development process.

Why Do We Need Informatics?

Informatics is a multidisciplinary field designed to organize biosample obtained data-points, patient data, analytics, and other relative information to improve the quality of health care services. Health information technologies (HIT) streamline large amounts of data. The information is then used to improve existing clinical processes.

With our current technological landscape, informatics complements many different aspects of our scientific community such as the ability to allow for a globalized networking and tissue banking resource.

Sampled bioinformatics is a viable analytical resource in the linkage or genotyping discrepancies within families, projects, or multiple data sets, thus enabling identification of candidate gene regions for common diseases. Additionally, we also partner with statistical geneticists and biostatisticians that collaborate on clinical study designs.

Personalized Medicine and Treatments

The Sampled research team embraces their role in to facilitating research into the links between genes and certain conditions. We know that decoding the connections between lifestyle choices and genetic biomarkers is the key to better health.

With today’s technological tools, genetic screening for complex health conditions can be more thoroughly studied and understood. Clinical studies have already identified the genetic variances linked to conditions such as:

• Crohn’s Disease
• Parkinson’s Disease
• Prostate Cancer
• Type 2 Diabetes

With the information learned, physicians can create individualized treatment plans. The NIH anticipates the development of a genomic-handbook for which one’s entire genome is made available for a more personalized health analysis.

Through the groundbreaking efforts of biomedical research, we can expect dramatic changes to the medical landscape. The forecasted changes will enhance patient engagement, as they will have the opportunity to receive customized therapeutic solutions which will, in turn, result in not only more positive outcomes but a more personalized patient experience.

Drug Development

Sample research is one of the early-stage components within the preclinical R&D phase of bringing new drugs to the market. The drug development process can be classified into three major steps: discovery, preclinical development, and clinical trial.

Preclinical development and discovery are the preliminary actions before the filing of an Investigational New Drug Application or an IND. If the IND is approved, the next phase is entering into a clinical trial (human-patient testing). Preclinical testing involves extensive pharmacological and toxicology testing.

As an integral part of this process, Sampled utilizes state of the art automated processes to help define the values used in compiling the IND application. Sampled preclinical development offerings include:

• Pre-validated and custom assay panels for genotyping and gene expression analysis of human and rodent samples.
• Platforms which include both traditional qPCR-based detection as well as high-throughput microfluidic chips and microarrays, all with fully automated processing.
• Assay development services for functional assays and high throughput screening using a variety of liquid handling and detection technologies.
• Service bundles include nucleic acid extraction, integrated sample QC, sample processing and fully automated construction of sequencing libraries.

Disease Understanding

Much of today’s biological research is devoted to a comprehensive understanding of disease states and their causes. For many advanced conditions, uncovering what happens on a molecular level is the key to improving existing therapies and developing new ones. Disease understanding involves decoding the relationships between DNA and mRNA and then applying this to novel drug discoveries and therapeutics.