Asterand Bioscience, A BioIVT Company

Three dimensional cell cultures are increasingly the method of choice for modeling cell behavior investigation of the effects of pre-clinical development compounds. In particular, multicellular 3D cell culture formats, often utilizing extracellular matrix (ECM) components for cell attachment / microenvironment influence, allow cells to form multi-layered structures or aggregates. There is increasing evidence that primary cells maintained in a 3D environment rather than conventional 2D culture more faithfully resemble the behavior and responsiveness of cells seen in intact tissues. PHASEZERO® provides established 3D cell culture platforms and 3D cell-based assay development, designing customized assays and relevant biological endpoints to meet specific project needs.
Features & Benefits
Ability to isolate primary cells from a variety of tissue types and representative diseases 2D and 3D models available culture formats include:

• 2D-Multiwell (6-96 well format)
• 2D-Transwells
• 3D-Spheroid (with or without soft matrix)
• 3D-Air-liquid interface (ALI)
• 3D-OrganDOT™ matrix free aggregates
• 3D-Raft™ physiological density matrix

BioIVT’s clinical specimens now include the ASTERAND Human Tissue Specimens, an invaluable source of high-quality, thoroughly characterized and validated human tissue, which can be used throughout the drug discovery and development process. As the leading provider of high quality human biospecimens and associated clinical information, we use rigorous criteria for the procurement and quality control of biospecimens. BioIVT has a worldwide network of hospitals working exclusively to procure high-quality biological samples for our onsite tissue bank. Our dynamic network of hospital procurement sites makes BioIVT unique in the biobanking industry and allows BioIVT to offer our clients many hard to procure treatment naïve tissue specimens in several formats.
Our extensive repository consists of over 300,000 human tissues with associated biofluids. This bank includes material that is prospectively obtained in a variety of formats including fresh frozen and FFPE as well as biofluids. Standard protocols are used to maintain the BioIVT repository and adhere to the highest standards of sample integrity, including difficult to procure treatment naïve tumor samples. Standard tissue products are generally available for next day shipping to keep your research moving.
Our custom procurement service offers human tissues and clinical data custom collected to meet unique research requirements within a wide range of disease categories. Samples are provided in multiple preserved formats or as fresh and unpreserved biospecimens. As a result, we deliver human tissues, biofluids, and accompanying clinical information in a manner that is most compatible with our client’s experimental design.
BioIVT collects every sample under IRB approved protocols, ensuring that strict ethical guidelines are followed to protect patient confidentiality and safety. Each sample has the patients consent for use in a wide range of research including the development of commercial products or services. The samples are identifiable only by barcodes to ensure an unbiased assessment as well as patient confidentiality.

BioIVT’s PHASEZERO Research Services Team will work with you to deliver actionable data to enable you to make more informed development decision surrounding the efficacy and safety of biological and chemical compounds and associated companion diagnostics. Our scientists have expertise in assay development and reporting across the following areas:
Target Expression – including qRT=PCR, mutation analysis, and NGS
Target Localization – including IHC, ISH/FISH, multiplex IHC/ISH, TMA construction
Therapeutic Effect – Including 2D / 3D Cell-based assay development, specific ORGANDOT culture studies for diabetes, liver fibrosis and oncology studies, ALI 3D studies for respiratory related studies
ADME-TOX – including Drug-drug interactions, metabolism, hepatoxicity, hepatic clearance,
Clinical Trial Assay – Including GCLP Assay Development, Clinical Sample Analyses

Disease modeling optimized for drug discovery, therapeutic and efficacy testing can be used for oncology, autoimmune disorders, injury, inflammation and more. BioIVT offers a range of cellular disease models that recapitulate disease morphology. In conjunction with our diseased and normal primary cells and established cell lines, our PHASEZERO scientists use their expertise in primary cell isolation and development of fit-for-purpose 2D and 3D models to provide functional assays and molecular / genomic approaches to study therapeutic effect, disposition, and safety. We have experience with a broad portfolio of culture platforms, across multiple cell types and disease areas. In particular, we apply our proprietary ORGANDOT™ culture to study diabetes, liver fibrosis and oncology.

BioIVT provides a wide range of molecular extractions for genomic research including DNA extraction (genomic DNA) and RNA extraction (total RNA and mRNA). Standard protocols can be used to obtain genomic DNA and total RNA. A wide range of commercially available DNA extraction and RNA extraction kits or custom protocols can be utilized to obtain samples for specific projects.

BioIVT provides a complete team of Histotechnicians, Histotechnologists and Board Certified Pathologists for all your sectioning, cyro-sectioning, staining and analysis needs.

HISTOLOGY SERVICES
Standard Services

• Sectioning
• IHC Staining

Custom Services

• IHC/Custom Staining
• Instrumentation Validation
• Assay Controls
• Specimen Embedding
• TMA Creation

Platforms

• Dako Autostainers
• Aperio AT2 Slide Scanner
• Auto Tissue Processors

PATHOLOGY SERVICES
Standard Services

• H&E with diagnosis confirmation

Custom Services

• Gross preperation of fresh specimens
• Identification of key tissue features
• Specimen marking

Platforms & Fees

• Aperio AT2 Slide Scanner
• Fees based on hourly rate

Our PHASEZERO® Research Services team has established expertise in both ViewRNA® and RNAscope® branched chain in situ hybridization techniques (ISH). Thorough assay development and optimization approaches allow us to effectively use these techniques to deliver high quality, biologically relevant data supporting human tissue based target and biomarker validation projects and diagnostic assay development.

We have expanded our capabilities in delivery of automated multiplexed data sets through the introduction of RNAscope 2.5. This approach is particularly suited to the evaluation of multiple targets in human tissues where robust antibodies are not available and increases both throughput and reproducibility through full automation.

Using multiplexed approaches such as these has clear application across many areas of disease biology, in particular for novel immuno-oncology approaches where understanding of specific immune cell interactions with solid tumors is paramount.

Features & Benefits
IHC assays are fully automated and run on the following machines:
• Dako Autostainer Plus (IQ/OQ/PQ validated)
• Ventana Discovery XT
• Leica BondRX machines

PHASEZERO’s XPRESSWAY gene expression profiles are quantitative gene transcripts expression patterns across 72 tissues (3 individual donors of each) representing the major organ systems of the human body, providing a reproducible and reliable rigid assay that is essential for target validation, safety profiling, and validation of animal models.
Using a rigorously controlled process, from tissue to data, PHASEZERO scientists have used the same highly sensitive, robust quantitative real-time PCR (qRT-PCR) methodology for the last 20 years ensuring reproducibility and reliability. To ensure reliability and repeatability across assays, we utilize a global standard curve inclusive of 81 genes, 150 individual standard curves, and 1476 data points.

Flow cytometry is a versatile and powerful technology for drug discovery and development researchers and BioIVT offers a wide-range of flow analysis capabilities and support to help you determine the best strategy for your needs. Our cellular and molecular analysis services are designed to accelerate your immune monitoring, epitope discovery, immunophenotyping or cell isolation projects. With off-the-shelf solutions to customized complex flow analysis, we serve as a strategic resource with extensive capabilities to develop, validate and deploy assays for the unique examination of various parameters.

Clinical development requires a wide range of flow analysis capabilities, each with its own optimization and validation. In order to support your R&D efforts, our flow cytometry services strategically align with specific drug development programs across a wide-range of therapeutic areas. BioIVT analyzes a multitude of specimen types including whole blood, fresh and frozen tumor or normal tissue, and PBMCs/BMMCs from pre-clinical model systems and human clinical trials. Combined with our Custom Tissue Procurement Service, our Flow Cytometry Sample Analysis Service is able to isolate unique and rare primary cell populations and characterize these populations according to your needs.

With an extensive tissue bank, we specifically customize your project to your needs. Our PHASEZERO® team has working protocols for targeting a wide range of oncology targets, plus routine immune cell markers. Our scientists can also develop custom profiles specific to your needs. We recently adopted the PerkinElmer Vectra® Polaris™ Automated Quantitative Pathology Imaging System to extend their services capabilities to drug and diagnostic development scientists. Capitalizing on over 20 years of expertise in human tissue-based research, PHASEZERO scientists are excited to extend this additional solution platform to our clients.

The Vectra Polaris system integrates seven-color multispectral imaging with whole-slide scanning in a simplified digital pathology workflow to support the quantification and analysis of tissue sections that are stained with multiple immunohistochemical stains.

Features & Benefits

IHC assays are fully automated and run on the following machines:
• Dako Autostainer Plus (IQ/OQ/PQ validated)
• Ventana Discovery XT
• Leica BondRX machines

Our PHASEZERO® division offers the latest generation branched-chain ISH technologies (ViewRNA® and RNAscope®), which represent a significant advance in sensitivity and throughput compared with traditional riboprobe ISH methods, for the detection and precise localization of cellular mRNA in human tissue. Ideally suited for target and biomarker validation and diagnostic assay development and testing, branched-chain ISH offers significant benefits.

Features & Benefits

• Rapid and cost-effective, branched-chain ISH accelerates target and biomarker validation
• Commercial availability of branched-chain ISH probes eliminates the need for additional up-front molecular biology work, required for traditional ISH.
• Increased sensitivity reduces the risk of missing relevant expression patterns by enabling the detection of low-level mRNA production
• Detecting extremely low levels of mRNA as compared with traditional ISH methodology, branched-chain ISH reduces the risk of false-negatives.
• Highly-specific assays make use of FFPE tissue possible
• Relying on the hybridization of large numbers of short oligonucleotide probe pairs, branched-chain ISH detects the less-well preserved mRNA in formalin-fixed, paraffin-embedded (FFPE) tissue as well as FFPE tissue microarrays (TMAs). - - Frozen sections can also be used and can offer greater sensitivity due to more complete RNA preservation.

ISH Multiplexing (ISH:ISH & ISH:IHC)

• Via ISH:ISH multiplexing, PhaseZERO is able to localize the expression of multiple mRNA targets in the same tissue.
• Via ISH:IHC multiplexing, PhaseZERO is able to localize mRNA and protein expression in the same tissue.

ISH Optimization, Validation, and Sensitivity

• PHASEZERO’s in situ hybridization protocols allow for the precise localization of mRNA in human tissue. Utilizing customer-specific assay development, optimization and validation with either commercially available probes or custom target probes, our ISH offers additional levels of security in the data interpretation, validation of expression to known gene expression and high sensitivity detection capabilities.

Increase Confidence in the Detection of Specific Binding

Our IHC service offers a stepwise and flexible approach. For each antibody/antigen combination, IHC assay conditions are initially optimized and validated for key parameters and endpoints including consideration of:

• Formalin-fixed, paraffin-embedded (FFPE) or frozen tissue sections
• Calorimetric or fluorescent endpoint
• Positive and negative control cells and/or tissues
• 2 antigen retrieval methodologies (FFPE) or 2 fixation techniques (frozen)
• 3 to 5 primary antibody concentrations with matching non-immune IgG isotype and ‘no primary antibody’ controls
• Appropriate system for detection of primary antibody binding, e.g. Dako EnVision™ FLEX System or Vector® ImmPRESS™ Excel Amplified HRP Polymer Staining System
• Positive control antibody included with every assay to validate detection reagents
• Expert analysis to confirm specificity and correct cellular location

Our 7-step process methodically optimizes and validates IHC protocol prior to experimental investigation.

1. IHC Analysis – Specific to the negative controls (no primary, non-immune) and staining of the appropriate cellular compartment
2. IHC Analysis – Demonstration of signal knock-down using specific peptide blocking
3. ICC – Predicted patterns and level of staining in positive and negative control cell lines
4. Western Blot – Detection of prominent band at the approximate expected molecular weight
5. Replication IHC – More than one antibody giving the same qualitative pattern of staining
6. Data Review – Similarity with published human tissue IHC data
7. RNAi – Demonstration of protein knock-down using RNAi (target expressing cell line)

Fully optimized and validated IHC assays are then used to investigate expression of the target protein(s) in a selected tissue panel, with peptide blocking experiments performed to further validate antibody specificity. Further antibody validation may include western blotting analysis or gene knock-down in suitable cell lines using RNAi or shRNA techniques.

BioIVT offers mutation services to support assay, diagnostic and drug development needs as well as assay validation. We are able to combine ready access to large cohorts of human tissues with expertise in the design and execution of NGS, qRT-PCR and FISH protocols. We can support the determination of SNVs (single nucleotide variants), Indels (Insertion or deletion of nucleotides), Fusions, and CNV (Copy Number Variants) as well as expression changes. qRT-PCR is an effective approach for determining the status of various somatic mutations in human tissue samples. These data aid in the selection of specific subsets of human tissue samples for future use / applications. We have provided such pre-screening services to enable tissue selections for KRAS and EGFR, among other mutations. Using FISH, we generate data that enable characterization of tissues for specific mutations such as HER2 or cMET gene amplifications or ROS/ALK gene rearrangements.

Features & Benefits

• Fully managed by in-house specialist
• Supported by large banked tissue specimen inventory with access to specific cohorts as needed

Access to multiple platforms:

• qPCR – SNV, Fusion, Expression changes – Tests specific known variants; confirmation of assays
• Sanger/Pyrosequencing – SNV – Test sections of genes or short genes, confirmation of assays
• NGS – SNV, CNV, Fusion – Explore large sections of genome, detection from multiple genes, detection of rare variants, information from multiple mutation types in one assay
• FISH – CNV, Fusion, Expression changes – Detection of specific gene sequences within chromosomes, identification of genomic status of oncology samples, analysis of gene amplification and mutation
• IHC – Fusion, Expression changes – Specific known variants or expression changes, does not require DNA or RNA to provide information

BioIVT offers mutation services to support assay, diagnostic and drug development needs as well as assay validation. We are able to combine ready access to large cohorts of human tissues with expertise in the design and execution of NGS, qRT-PCR and FISH protocols. We can support the determination of SNVs (single nucleotide variants), Indels (Insertion or deletion of nucleotides), Fusions, and CNV (Copy Number Variants) as well as expression changes. qRT-PCR is an effective approach for determining the status of various somatic mutations in human tissue samples. These data aid in the selection of specific subsets of human tissue samples for future use / applications. We have provided such pre-screening services to enable tissue selections for KRAS and EGFR, among other mutations. Using FISH, we generate data that enable characterization of tissues for specific mutations such as HER2 or cMET gene amplifications or ROS/ALK gene rearrangements.

Features & Benefits

• Fully managed by in-house specialist
• Supported by large banked tissue specimen inventory with access to specific cohorts as needed

Access to multiple platforms:

• qPCR – SNV, Fusion, Expression changes – Tests specific known variants; confirmation of assays
• Sanger/Pyrosequencing – SNV – Test sections of genes or short genes, confirmation of assays
• NGS – SNV, CNV, Fusion – Explore large sections of genome, detection from multiple genes, detection of rare variants, information from multiple mutation types in one assay
• FISH – CNV, Fusion, Expression changes – Detection of specific gene sequences within chromosomes, identification of genomic status of oncology samples, analysis of gene amplification and mutation
• IHC – Fusion, Expression changes – Specific known variants or expression changes, does not require DNA or RNA to provide information

BioIVT offers a comprehensive portfolio of peripheral blood mononuclear cells (PBMCs) from a variety of animal species. These cells are manufactured with optimized methods to ensure a high quality product with superior viability, purity and functionality. Utilization of our cell products can yield a faster time-to-market as less time will be spent on sample preparation and leaving our clients to focus on more technically challenging end point assays.
Researchers can receive PBMCs and other fresh material less than 24 hours after collection. These cell isolations can either be shipped fresh overnight for immediate use, or cryopreserved for future scheduled work.
-PBMCs can be prepared from a variety of source matrices: vacutainer collection, buffy coat, leukopak and more
-Further processing performed, including RBC lysis, washing, and counting
-Aliquoting by cell count
BioIVT also prospectively collects patient samples that can meet study-specific inclusion and exclusion criteria. All collections are conducted under IRB-approved protocols, and all donors sign informed consent forms where applicable. Samples are fully characterized and come complete with demographic and medical data, as recorded on case report forms at the time of collection.

Biofluids are available as both banked inventory or custom collection with associated clinical data such as medication, cancer or disease stage, clinical lab values such as cholesterol and liver function, RF value and viral serology. Available matrices include - Whole blood/ Serum / Plasma, Sputum, Synovial fluid, Cerebrospinal fluid (CSF), PAP smears, Bone marrow, Cord blood, Oral swabs/Saliva/Sputum, Tears, Urine, Feces

Customized collections kits:
Donor specifications, protocols, collection containers and more
Repeat donor collections for longitudinal studies
Access to unique or rare patient populations, including pediatric and pregnant donors
Matched sets from individual donors

Biofluids are available as both banked inventory or custom collection with associated clinical data such as medication, cancer or disease stage, clinical lab values such as cholesterol and liver function, RF value and viral serology.

Customized collections kits:
Donor specifications, protocols, collection containers and more
Matched sets from individual donors

Biofluids are available as both banked inventory or custom collection with associated clinical data such as medication, cancer or disease stage, clinical lab values such as cholesterol and liver function, RF value and viral serology. Available matrices include - Whole blood/ Serum / Plasma.
Customized collections kits:
Donor specifications, protocols, collection containers and more
Repeat donor collections for longitudinal studies
Access to unique or rare patient populations, including pediatric and pregnant donors
Matched sets from individual donor

Urine consists primarily of water, but also contains an assortment of inorganic salts and organic compounds, including proteins, hormones, and a wide range of metabolites. As a sterile, non-invasive biological fluid, urine is becoming a favored sample type for biomarker research. Not only is it being used to detect kidney disease, but scientists have begun to identify urine cancer biomarkers that can be used for early screening and monitoring.

Features & Benefits
-Donor demographics provided for all lots
-Collection protocols can be tailored according to client specification
-Large lot sizes available from individual or pooled donors

BioIVT offers a comprehensive portfolio of peripheral blood mononuclear cells (PBMCs) from a variety of animal species. These cells are manufactured with optimized methods to ensure a high quality product with superior viability, purity and functionality. Utilization of our cell products can yield a faster time-to-market as less time will be spent on sample preparation and leaving our clients to focus on more technically challenging end point assays.

Researchers can receive PBMCs and other fresh material less than 24 hours after collection. These cell isolations can either be shipped fresh overnight for immediate use, or cryopreserved for future scheduled work.
-PBMCs can be prepared from a variety of source matrices: vacutainer collection, buffy coat, leukopak and more
-Further processing performed, including RBC lysis, washing, and counting
-Aliquoting by cell count

BioIVT also prospectively collects patient samples that can meet study-specific inclusion and exclusion criteria. All collections are conducted under IRB-approved protocols, and all donors sign informed consent forms where applicable. Samples are fully characterized and come complete with demographic and medical data, as recorded on case report forms at the time of collection.

BioIVT has a network of over 200 IRB-approved facilities providing access to a diverse array of specimens. Our growing clinical network is made up of physicians, research groups, hospitals, and reference labs that we work closely with to provide tailored specimen collections to meet your research needs.
Based on diagnosis and standard of care, we are able to provide punch/biopsy samples across a diverse population. Please contact us to find out what is currently in inventory for your specific needs or to design a custom collection process.

Biofluids are available as both banked inventory or custom collection with associated clinical data such as medication, cancer or disease stage, clinical lab values such as cholesterol and liver function, RF value and viral serology. Available matrices include - Whole blood/ Serum / Plasma,
Customized collections kits:
Donor specifications, protocols, collection containers and more
Repeat donor collections for longitudinal studies
Access to unique or rare patient populations, including pediatric and pregnant donors
Matched sets from individual donors

Our clients can access tissue- and blood-derived cell products from patient populations across key disease states. BioIVT offers primary human diseased and normal lung parenchymal and bronchial epithelial cells (huBECs) from COPD, IPF, CF (including genotype), Asthma and other diseased populations as well as primary cancer associated fibroblasts (huCAFS) and epithelial cells from many oncology indications. If the cell product you need isn’t currently in our portfolio, we’ll work with you to develop customized product or cell types to meet your specific requirements. We will tailor our procedures to meet your tissue, donor or product format needs. In addition, our cancer cell lines have the fidelity of primary cells.

BioIVT offers a comprehensive portfolio of peripheral blood mononuclear cells (PBMCs) from a variety of animal species. These cells are manufactured with optimized methods to ensure a high quality product with superior viability, purity and functionality. Utilization of our cell products can yield a faster time-to-market as less time will be spent on sample preparation and leaving our clients to focus on more technically challenging end point assays.

Researchers can receive PBMCs and other fresh material less than 24 hours after collection. These cell isolations can either be shipped fresh overnight for immediate use, or cryopreserved for future scheduled work.

PBMCs can be prepared from a variety of source matrices: vacutainer collection, buffy coat, leukopak and more
Further processing performed, including RBC lysis, washing, and counting
Aliquoting by cell count
BioIVT also prospectively collects patient samples that can meet study-specific inclusion and exclusion criteria. All collections are conducted under IRB-approved protocols, and all donors sign informed consent forms where applicable. Samples are fully characterized and come complete with demographic and medical data, as recorded on case report forms at the time of collection

BioIVT now has a network of over 200 IRB-approved facilities providing access to a diverse array of specimens. Our growing clinical network is made up of physicians, research groups, hospitals, and reference labs that we work closely with to provide tailored specimen collections to meet your research needs.

ASTERAND™ Human Tissue Specimens

• Over 175,000 tissue samples collected in a standard format, banked and available for immediate shipment
• Formats: FFPE, frozen, plasma, serum, whole blood and matched sets of donor specimens
  Rigorous QC:
• Specimens reviewed by board certified pathology to confirm diagnosis and specimen quality
• Clinical data review of over 200 data points
• Ethical and regulatory traceability for each case

Available tumors include Solid Tumor Indications (such as adenocarcinoma and squamous cell carcinoma of most organs – Lung, Breast, Colorectal, Prostate, Pancreas, Head & Neck, Gynecological, Urogenital, Brain and Skin), Heme-oncology Indications (such as Lymphoma, Leukemia, Myeloma, and other disorders), and Sarcoma Indications (such as Mesothelioma, GIST, Chondrosarcoma, Osteosarcoma, Rhabdomyosarcoma and others).

BioIVT has the ability to offer tissues in various matrix formats, such as fresh, FFPE, Fresh Frozen or OCT Embedded. In addition, BioIVT has extended capabilities to collect both blood-derived biofluids, with coagulant of choice, and non-blood derived biofluids, including respiratory, reproductive, and gastrointestinal. With the ability to provide matched sets from a single donor, longitudinal time points from a single donor, pre-treatment/Naïve cohorts as well as other client-specific exclusion/inclusion criteria, BioIVT has the specimen you need for your research.

In addition, BioIVT has immortalized cell lines, primary cancer-associated fibroblasts and epithelial cells, dissociated tumor cells, and purified immune cells.

Our PHASEZERO Research Services Team is available to work with you to accelerate your research. Whether you need disease modeling with 2D and 3D cell-based assays drug target validation with immunohistochemistry or in situ hybridization, or safety analysis, our experienced team provides actionable data for you.

BioIVT now has a network of over 200 IRB-approved facilities providing access to a diverse array of specimens. Our growing clinical network is made up of physicians, research groups, hospitals, and reference labs that we work closely with to provide tailored specimen collections to meet your research needs.
ASTERAND™ Human Tissue Specimens

• Over 175,000 tissue samples collected in a standard format, banked and available for immediate shipment
• Formats: FFPE, frozen, plasma, serum, whole blood and matched sets of donor specimens
  Rigorous QC:
• Specimens reviewed by board certified pathology to confirm diagnosis and specimen quality
• Clinical data review of over 200 data points
• Ethical and regulatory traceability for each case

BioIVT now has a network of over 200 IRB-approved facilities providing access to a diverse array of specimens. Our growing clinical network is made up of physicians, research groups, hospitals, and reference labs that we work closely with to provide tailored specimen collections to meet your research needs.
ASTERAND™ Human Tissue Specimens

• Over 175,000 tissue samples collected in a standard format, banked and available for immediate shipment
• Formats: FFPE, frozen, plasma, serum, whole blood and matched sets of donor specimens
  Rigorous QC:
• Specimens reviewed by board certified pathology to confirm diagnosis and specimen quality
• Clinical data review of over 200 data points
• Ethical and regulatory traceability for each case

BioIVT’s clinical specimens now include the ASTERAND Human Tissue Specimens, an invaluable source of high-quality, thoroughly characterized and validated human tissue, which can be used throughout the drug discovery and development process. As the leading provider of high quality human biospecimens and associated clinical information, we use rigorous criteria for the procurement and quality control of biospecimens. BioIVT has a worldwide network of hospitals working exclusively to procure high-quality biological samples for our onsite tissue bank. Our dynamic network of hospital procurement sites makes BioIVT unique in the biobanking industry and allows BioIVT to offer our clients many hard to procure treatment naïve tissue specimens in several formats.

Our extensive repository consists of over 300,000 human tissues with associated biofluids. This bank includes material that is prospectively obtained in a variety of formats including fresh frozen and FFPE as well as biofluids. Standard protocols are used to maintain the BioIVT repository and adhere to the highest standards of sample integrity, including difficult to procure treatment naïve tumor samples. Standard tissue products are generally available for next day shipping to keep your research moving.

Our custom procurement service offers human tissues and clinical data custom collected to meet unique research requirements within a wide range of disease categories. Samples are provided in multiple preserved formats or as fresh and unpreserved biospecimens. As a result, we deliver human tissues, biofluids, and accompanying clinical information in a manner that is most compatible with our client’s experimental design.

BioIVT collects every sample under IRB approved protocols, ensuring that strict ethical guidelines are followed to protect patient confidentiality and safety. Each sample has the patients consent for use in a wide range of research including the development of commercial products or services. The samples are identifiable only by barcodes to ensure an unbiased assessment as well as patient confidentiality.

BioIVT’s selection of immortalized cell lines will further your research in the mechanisms of cancer growth and progression. Our cell lines derive directly from freshly isolated solid tumors, including breast and prostate tissues as well as hematological samples. Each cell line purchased includes clinical data delivered with the cell aliquots. Our stringent quality control processes requires authentication including sterility testing, viability, and plating efficiency determined by lot. Immortalized cell lines are cryopreserved in 1 x 106 ampules.

Breast Cell Lines

Through licensing agreements with the University of Michigan and the Karmanos Cancer Institute, BioIVT provides 11 well-characterized human breast cancer cell lines to assist in breast cancer research.

Ten SUM cell lines derived in Steve Ethier’s lab while present at the University of Michigan are available for purchase. Each cell line, from a single patient, represents a different subtype of breast cancer. All of the currently known oncogenes with altered expression patterns in breast cancer, in various combinations, are represented and characterized in the SUM lines. Furthermore, these cell lines have been described in over 50 peer-reviewed publications, describing isolation and growth conditions, gene expression data via Affymetrix GeneChips, and biomolecular markers, such as estrogen receptor and Her2 status.

Prostate Cell Lines **

BioIVT offers three pairs of prostate tumor and normal cell lines. Researchers at the Karmanos Cancer Institute, Onyvax Ltd., and Asterand collaborated to derive these cell lines from tumors and adjacent “normal” tissues obtained at the time of prostatectomy. These prostate cell lines were immortalized via replication-defective retrovirus transferring the transforming HPV16 or HPV18 E6 and E7 genes.

**All prostate cell lines were immortalized were by exposing the cells to a replication-defective retrovirus transferring the transforming HPV16 or HPV18 E6 and E7 genes.

Hematopoietic Malignancies Cell Lines

Through a licensing agreement with the Barbara Ann Karmanos Cancer Institute, BioIVT provides well characterized human cell lines derived from patients with hematopoetic malignancies. These cell lines, developed by Doctors Ayad Al-Katib and Ramzi Mohammad, will be of interest to researchers seeking a cure for lymphoma, leukemia, pancreatic cancer, and macroglobulinema.

BioIVT provides a complete team of Histotechnicians, Histotechnologists and Board Certified Pathologists for all your sectioning, cyro-sectioning, staining and analysis needs.

Histology Services

Standard Services
-Sectioning
-IHC Staining

Custom Services
-IHC/Custom Staining
-Instrumentation Validation
-Assay Controls
-Specimen Embedding
-TMA Creation

Platforms
-Dako Autostainers
-Aperio AT2 Slide Scanner
-Auto Tissue Processors

Pathology Services

Standard Services
-H&E with diagnosis confirmation

Custom Services
-Gross preperation of fresh specimens
-Identification of key tissue features
-Specimen marking

Platforms & Fees
-Aperio AT2 Slide Scanner
-Fees based on hourly rate

Our PHASEZERO® scientists have over 20 years of experience performing human tissue-based IHC, with a specialty in custom assay development for commercially-available or client-generated antibodies and binding molecules (biosimilars, bi-specifics and antibody-drug conjugates). Our scientists apply rigorous approaches to deliver intelligent assay design, optimized and robust immunostaining protocols and expert data interpretation.

Features & Benefits

IHC assays are fully automated and run on the following machines:
• Dako Autostainer Plus (IQ/OQ/PQ validated)
• Ventana Discovery XT
• Leica BondRX machines

Our PHASEZERO® scientists have over 20 years of experience performing human tissue-based IHC, with a specialty in custom assay development for commercially-available or client-generated antibodies and binding molecules (biosimilars, bi-specifics and antibody-drug conjugates). Our scientists apply rigorous approaches to deliver intelligent assay design, optimized and robust immunostaining protocols and expert data interpretation.

Features & Benefits

IHC assays are fully automated and run on the following machines:
• Dako Autostainer Plus (IQ/OQ/PQ validated)
• Ventana Discovery XT
• Leica BondRX machines

BioIVT’s PHASEZERO Research Services Team applies 20 years of experience in immunohistochemical studies to provide Tissue Cross Reactivity (TCR) services to Good Laboratory Practice (GLP). Our team ensures that a tailored scientific approach results in the delivery of high quality data within defined timelines.

Quality of the tissue used affects the confidence in TCR study results. BioIVT’s extensive human tissue biorepository and supporting tissue supply network allows immediate access to all of the tissue types required by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for TCR safety studies. Because we manage our own tissue network and have a team of board certified pathologists, we are able to provide our clients with the assurance that the well characterized tissues used in studies are of the highest quality. All tissues are acquired according to BioIVT’s ethics, consent and quality protocols and are stored in our repository for immediate access.

All tissues are specially qualified by us for use in GLP studies with respect to their quality and background clinical data.

Our team will provide a custom service to meet the particular requirements for your therapeutic antibody or binding molecule (Test Item). Furthermore, we provide cost-effective assay development and validation studies for making confident decisions on the suitability and assay parameters to deploy for assessing your Test Item’s potential cross reactivity.

Our PHASEZERO® Research Services team has established expertise in both ViewRNA® and RNAscope® branched chain in situ hybridization techniques (ISH). Thorough assay development and optimization approaches allow us to effectively use these techniques to deliver high quality, biologically relevant data supporting human tissue based target and biomarker validation projects and diagnostic assay development.

We have expanded our capabilities in delivery of automated multiplexed data sets through the introduction of RNAscope 2.5. This approach is particularly suited to the evaluation of multiple targets in human tissues where robust antibodies are not available and increases both throughput and reproducibility through full automation.

Using multiplexed approaches such as these has clear application across many areas of disease biology, in particular for novel immuno-oncology approaches where understanding of specific immune cell interactions with solid tumors is paramount.

Features & Benefits
IHC assays are fully automated and run on the following machines:
• Dako Autostainer Plus (IQ/OQ/PQ validated)
• Ventana Discovery XT
• Leica BondRX machines

Tissue Microarrays (TMAs) provide our customer with a screening tool representing multiple donors. TMAs can discover new protein or genetic markers and can be tools in diagnostic development and validation. Tissue arrays can also measure protein, RNA or DNA markers, and are compatible with immunohistochemistry (IHC) staining and potentially in situ hybridization (ISH). Standard human derived TMAs of tumor and normal samples are available for research studies (from FFPE or Frozen tissue). Products are available both as sections as well as whole block. Custom TMAs are available upon request.

BioIVT Tissue Microarrays (TMAs), specifically designed for drug discovery and clinical marker research, can be used in development of diagnostics, therapeutics and for the study of new gene/protein markers. Each TMA is accompanied by a representative map and key that includes clinical and donor demographics. All specimens are collected using consented donors under IRB approval and are pre-reviewed by a board certified pathologist to confirm tissue type and diagnosis.

Our high-density, high-quality oncology and normal tissue FFPE microarrays are currently available in three standard formats:

• Core4OncArray representing over 120 cases (360 0.6mm cores) of breast, prostate, lung and colon cancer with representative normal tissue from each organ
• CoreNormArray representing a FDA panel of 36 normal tissues from 3 donors (324 0.6mm cores)
• CoreOncArray representing 12 different tumor types with associated normal controls with 72 unique samples (144 1.0mm cores)
• CoreLuFibArray representing IPF (9), PF (4) and normal (4) lung samples, with 34 cores

In addition, the following TMAs are available:

• fCoreFDAArray representing 36 FDA/EMA cross-reactivity tissues arranged across three separate frozen arrays, each containing 12 non-diseased human tissues in duplicate, from three donors (72 1.5mm cores)
• Custom designed microarrays are available through our PHASEZERO® services

Features & Benefits

• All specimens collected using consented donros under IRB approval
• All specimens are pre-reviewed by a board certified pathologist to confirm tissue type and diagnosis
• High-density, high-quality with normal tissues on same TMA
• Map and Key of each TMA available that includes clinical and donor demographics

Our scientists provide custom isolations of mammalian fibroblasts from solid tumors, normal tissue or diseased tissue as well as peripheral blood mononucleocytes (PBMCs).

Our scientists provide custom isolations of mammalian fibroblasts from solid tumors, normal tissue or diseased tissue as well as peripheral blood mononucleocytes (PBMCs).
Primary Cells
-Available Primary Cells
Cancer Associated Fibroblasts (HuCAFs)
Lung Epithelial Cells (HuBECs)
Pulmonary Fibroblasts
Chondrocytes
Synovial Fibroblasts

-Custom Services
Isolation of Cells from:
Whole Blood
Tissue
Bone Marrow Aspirates
Synovial Fluids

Methods & Techniques
Tissue Dissociation
Density Gradient

BioIVT provides a complete team of Histotechnicians, Histotechnologists and Board Certified Pathologists for all your sectioning, cyro-sectioning, staining and analysis needs.

HISTOLOGY SERVICES
Standard Services

• Sectioning
• IHC Staining

Custom Services

• IHC/Custom Staining
• Instrumentation Validation
• Assay Controls
• Specimen Embedding
• TMA Creation

Platforms

• Dako Autostainers
• Aperio AT2 Slide Scanner
• Auto Tissue Processors

PATHOLOGY SERVICES
Standard Services

• H&E with diagnosis confirmation

Custom Services

• Gross preperation of fresh specimens
• Identification of key tissue features
• Specimen marking

Platforms & Fees

• Aperio AT2 Slide Scanner
• Fees based on hourly rate

BioIVT offers mutation services to support assay, diagnostic and drug development needs as well as assay validation. We are able to combine ready access to large cohorts of human tissues with expertise in the design and execution of NGS, qRT-PCR and FISH protocols. We can support the determination of SNVs (single nucleotide variants), Indels (Insertion or deletion of nucleotides), Fusions, and CNV (Copy Number Variants) as well as expression changes. qRT-PCR is an effective approach for determining the status of various somatic mutations in human tissue samples. These data aid in the selection of specific subsets of human tissue samples for future use / applications. We have provided such pre-screening services to enable tissue selections for KRAS and EGFR, among other mutations. Using FISH, we generate data that enable characterization of tissues for specific mutations such as HER2 or cMET gene amplifications or ROS/ALK gene rearrangements.

Features & Benefits

• Fully managed by in-house specialist
• Supported by large banked tissue specimen inventory with access to specific cohorts as needed

Access to multiple platforms:

• qPCR – SNV, Fusion, Expression changes – Tests specific known variants; confirmation of assays
• Sanger/Pyrosequencing – SNV – Test sections of genes or short genes, confirmation of assays
• NGS – SNV, CNV, Fusion – Explore large sections of genome, detection from multiple genes, detection of rare variants, information from multiple mutation types in one assay
• FISH – CNV, Fusion, Expression changes – Detection of specific gene sequences within chromosomes, identification of genomic status of oncology samples, analysis of gene amplification and mutation
• IHC – Fusion, Expression changes – Specific known variants or expression changes, does not require DNA or RNA to provide information

Three dimensional cell cultures are increasingly the method of choice for modelling cell behaviour investigation of the effects of pre-clinical development compounds. In particular, multicellular 3D cell culture formats, often utilising extracellular matrix (ECM) components for cell attachment / microenvironment influence, allow cells to form multi-layered structures or aggregates. There is increasing evidence that primary cells maintained in a 3D environment rather than conventional 2D culture more faithfully resemble the behaviour and responsiveness of cells seen in intact tissues. BioIVT provides established 3D cell culture platforms and 3D cell-based assay development, designing customized assays and relevant biological endpoints to meet specific project needs.

BioIVT offers both established Organotypic 3D assay platforms, including our proprietary OrganDOT™ platform, as well as those in development for liver fibrosis and oncology studies.

Established Organotypic 3D Assay Platforms
Human Pancreatic Islets for the Study of Type 2 Diabetes
Using our proprietary OrganDOT™ platform, BioIVT developed the isletOrganDOT™ model.
Human Bronchial Epithelial Cells for the Study of Respiratory Function
BioIVT has extensive experience in the preparation of organotypic cultures of human bronchial epithelium, using air-liquid interface (ALI) conditions to generate highly differentiated, mucociliary cultures that mimic many of the features of the airway epithelium. This platform allows us to establish appropriate in vitro assays for profiling the functional activity of novel therapeutics.

Organotypic 3D Assay Platforms in Development
Liver Fibrosis
BioIVT received funding in September 2014 from the UK Technology Strategy Board (Innovate UK) to lead the development of a 3D multicellular liver fibrosis model. We are collaborating with the University of Manchester for the parallel evaluation of a matrix-free (OrganDOT™) and matrix-based (RAFT™) platform.
Oncology
BioIVT is developing 3D human primary multicellular oncology models using the OrganDOT™ platform. Initial development work has been

BioIVT has established expertise in the isolation and culture of human primary cells and in the development of human primary cell-based assays (both 2D and 3D) to support late lead optimization/candidate selection stage compound evaluation.

Use of Native Human Tissues and Cells Provides Relevant Data for Understanding the Behavior of Compounds at Native Human Receptors
Non-human tissues and cultured cells and human recombinant cell lines are used effectively for screening and the initial identification of compounds with desired pharmacological effects. Moreover, using human tissues and primary cells ultimately provides translational data to support the selection of those compounds with the best opportunity for success in the clinic.

Access to a Range of Different Human Tissue Types and Diseases Enables Generation of Translational Data Across Key Disease Areas
Our core cell-based assay disease areas are inflammation, respiratory and metabolic, with development of 2D and 3D cell culture models ongoing in oncology and fibrosis.

2D and 3D Culture Expertise Allows Combination of the Most Appropriate Models and Endpoints for Maximum Translational Impact

We also offer a variety of biochemical assay endpoints for profiling compound effects in intact human tissues, freshly isolated human cells and subcellular fractions. Custom cell based assays using primary human cells can be developed and validated to meet client’s specific requirements.
Included culture formats include: 2D – Multiwell (6-96 well), 2D-Transwells, 3D-Spheroid (with/without soft matrix), 3D-Air-liquid interface, 3D-OrganDOT™ matrix free aggregates, and 3D-RAFT™ physiological density matrix

Assay Types/Endpoints include: Cytokine/Mediator Release, Cell Viability/Proliferation, Apoptosis, Changes in Gene Expression, Enzyme Activity/Release, Barrier Permeability, Cell Migration, IHC/ICC

In addition to our respiratory disease cell panel, other examples of primary cells that have been isolated for custom projects include: BLOOD – PBMCs, monocytes, lymphocyte, neutrophils; SKIN – keratinocytes-fibroblasts; LUNG – alveolar macrophages, alveolar type II cells, smooth muscle cells, tumor epithelial cells, cancer-associated fibroblasts; KIDNEY – Proximal tubule cells; BREAST – tumor epithelial cells, cancer-associated fibroblasts; COLON – tumor epithelial cells, cancer-associated fibroblasts

Using our qRT-PCR platform we provide robust, quantitative gene expression data in standard and custom cohorts of diseased and non-diseased human tissues. We are also able to characterize tissue cohorts for specific somatic mutations, like KRAS, EGFR, AKT using a qRT-PCR based approach.

Using our qRT-PCR platform we provide robust, quantitative gene expression data in standard and custom cohorts of diseased and non-diseased tissues. The data is used to support target selection, to understand tissue specific, disease relevant or population differences in gene expression. Some additional purposes include to alert investigators to potential safety liabilities and to validate animal models. We are also able to characterize tissue cohorts for specific somatic mutations, like KRAS, EGFR, AKT using a qRT-PCR based approach.

PHASEZERO offers custom PCR analysis for clients who wish to investigate the level of expression of a target(s) in cohorts of specific normal and/or diseased tissue types. Tissues used can be specific by the client (prospective collection, BioIVT sourced or client-owned). Our scientists can start with the tissue specimens and preform the DNA/RNA extraction or start with client supplied DNA/RNA. We then QC the nucleic acid and perform the qRT-PCR.

Features & Benefits

• Design of TaqMan® and MGB primer probes
• Low density arrays
• RNA extraction and quality control
• XPRESSWAY�™ profiles or custom gene expression profiling

To address an area of increasing need of our pharma and diagnostics clients, we are able to combine ready access to large cohorts of human tissues with expertise in the design and execution of FISH protocols. The data generated enable characterization of tissues for specific mutations such as Her2 or cMET gene amplifications or ROS or ALK gene rearrangements.

The surge in research and development activities focused on personalized medicine coincides with the rapidly decreasing cost of human genome mapping and a greater understanding of disease heterogeneity. As a researcher, you struggle with high attrition rate based on lack of clinical efficacy. It is crucial to your studies to utilize ethically collected, well-characterized human specimens and comprehensive tissue-based research services.

Look to BioIVT for expertise in the processes required for the ethical acquisition of biospecimens that cover a wide range of disease states and the protocols needed for the production of reliable data.

We offer:
• Unparalleled access to over 200 IRB-approved collection sites
• Access to a comprehensive array of biospecimens across multiple sample types and disease indications
• Standardization and quality control coupled with the ability to customize collections to meet your specific criteria and research needs

The PHASEZERO® Research Services team delivers high quality molecular pathology data to support the selection and validation of drug targets and biomarkers in human tissues. In addition, the approaches we provide are ideally suited for diagnostic assay development and testing. Our molecular pathology platforms are used to great effect as endpoints for our human primary cell based assays. This allows changes in the expression of key targets to be determined following treatment of human cells with novel therapeutic agents.

Our team of scientists offer routine RNA (total RNA and mRNA), DNA (genomic DNA) and protein isolation from flash frozen tissue, FFPE and cells. We also provide mutation analysis on several of our products as well as a custom service.
Standard protocols can be used to obtain genomic DNA and total RNA. A wide range of commercially available DNA extraction and RNA extraction kits or custom protocols can be utilized to obtain samples for specific projects. Each RNA extraction is analyzed on an Agilent 2100 and provided with a quality control report featuring an RNA Integrity Number (RIN). The Agilent 2100 software assigns an integrity number (0-10) to an RNA sample. The Agilent 2100 identifies the presence or absence of degradation of products and interprets the quality of the specimen. DNA quality is analyzed by gel electrophoresis. Quantitation it performed by spectrophotometry (Nanodrop) and fluorometry (Qubit). Careful qualitative and quantitative analysis will guarantee high quality specimens and yield high quality research results.
Protein Lysates are extracted using a Modified RIPA Buffer protocol.

BioIVT is a leading global provider of high-quality biological specimens and value-added services. We specialize in control and disease state samples including human and animal tissues, cell products, blood and other biofluids. Our unmatched portfolio of clinical specimens directly supports precision medicine research and the effort to improve patient outcomes by coupling comprehensive clinical data with donor samples. By combining our technical expertise, exceptional customer service, and unparalleled access to biological specimens, BioIVT serves the research community as a trusted partner in ELEVATING SCIENCE.

Our team of scientists offer routine DNA (genomic DNA) isolation from flash frozen tissue, FFPE and cells. We also provide mutation analysis on several of our products as well as a custom service.

Standard protocols can be used to obtain genomic DNA. A wide range of commercially available DNA extraction kits or custom protocols can be utilized to obtain samples for specific projects. DNA quality is analyzed by gel electrophoresis. Quantitation it performed by spectrophotometry (Nanodrop) and fluorometry (Qubit). Careful qualitative and quantitative analysis will guarantee high quality specimens and yield high quality research results.

Our scientists provide custom isolations of mammalian fibroblasts from solid tumors, normal tissue or diseased tissue as well as peripheral blood mononucleocytes (PBMCs).

Primary Cells
-Available Primary Cells
Cancer Associated Fibroblasts (HuCAFs)
Lung Epithelial Cells (HuBECs)
Pulmonary Fibroblasts
Chondrocytes
Synovial Fibroblasts
-Custom Services
Isolation of Cells from:
Whole Blood
Tissue
Bone Marrow Aspirates
Synovial Fluids

Methods & Techniques
Tissue Dissociation
Density Gradient
Magnetic Separation
Flow Cytometry

Our BioIVT PHASEZERO® scientists has established expertise in the isolation and culture of human primary cells and in the development of human primary cell-based assays (both 2D and 3D) to support late lead optimization/candidate selection stage compound evaluation. Non-human tissues and cultured cells and human recombinant cell lines are used effectively for screening and the initial identification of compounds with desired pharmacological effects. Moreover, using human tissues and primary cells ultimately provides translational data to support the selection of those compounds with the best opportunity for success in the clinic.

Human Tissue Types
Our core cell-based assay disease areas are inflammation, respiratory and metabolic, with development of 2D and 3D cell culture models ongoing in oncology and fibrosis.

Additional examples of primary cells that have been isolated for custom projects include:

• Blood – PBMC, monocytes, lymphocytes and neutrophils
• Skin – Keratinocytes, fibroblasts
• Lung – Alveolar macrophages, alveolar type II cells, smooth muscle cells, tumor epithelial cells, cancer-associated fibroblasts
• Kidney – Proximal tubule cells
• Breast – Tumor epithelial cells, cancer-associated fibroblasts
• Colon – Tumor epithelial cells, cancer-associated fibroblasts

Features & Benefits
Ability to isolate primary cells from a variety of tissue types and representative diseases 2D and 3D models available culture formats include:

• 2D-Multiwell (6-96 well format)
• 2D-Transwells
• 3D-Spheroid (with or without soft matrix)
• 3D-Air-liquid interface (ALI)
• 3D-OrganDOT™ matrix free aggregates
• 3D-Raft™ physiological density matrix

The surge in research and development activities focused on personalized medicine coincides with the rapidly decreasing cost of human genome mapping and a greater understanding of disease heterogeneity. As a researcher, you struggle with high attrition rate based on lack of clinical efficacy. It is crucial to your studies to utilize ethically collected, well-characterized human specimens and comprehensive tissue-based research services.
Look to BioIVT for expertise in the processes required for the ethical acquisition of biospecimens that cover a wide range of disease states and the protocols needed for the production of reliable data.

We offer:

BioIVT now has a network of over 200 IRB-approved facilities providing access to a diverse array of specimens. Our growing clinical network is made up of physicians, research groups, hospitals, and reference labs that we work closely with to provide tailored specimen collections to meet your research needs.

ASTERAND Human Tissue Specimens
Over 175,000 tissue samples collected in a standard format, banked and available for immediate shipment
Formats: FFPE, frozen, plasma, serum, whole blood and matched sets of donor specimens
Rigorous QC:

• Specimens reviewed by board certified pathology to confirm diagnosis and specimen quality
• Clinical data review of over 200 data points
• Ethical and regulatory traceability for each case
• Biofluid Specimens

Biofluids are available as both banked inventory or custom collection with associated clinical data such as medication, cancer or disease stage, clinical lab values such as cholesterol and liver function, RF value and viral serology. Available matrices include - Whole blood/ Serum / Plasma, Sputum, Synovial fluid, Cerebrospinal fluid (CSF), PAP smears, Bone marrow, Cord blood, Oral swabs/Saliva/Sputum, Tears, Urine, Feces

Customized collections kits:

• Donor specifications, protocols, collection containers and more
• Repeat donor collections for longitudinal studies
• Access to unique or rare patient populations, including pediatric and pregnant donors
• Matched sets from individual donors

ADME/DMPK Studies Services

BioIVT’s PHASEZERO Research Services Team will work with you to deliver actionable data to enable you to make more informed development decision surrounding the efficacy and safety of biological and chemical compounds and associated companion diagnostics. Our scientists have expertise in assay development and reporting across the following areas:
Target Expression – including qRT=PCR, mutation analysis, and NGS
Target Localization – including IHC, ISH/FISH, multiplex IHC/ISH, TMA construction
Therapeutic Effect – Including 2D / 3D Cell-based Assay development, specific ORGANDOT culture studies for diabetes, liver fibrosis and oncology studies, ALI 3D studies for Respiratory related studies
ADME-TOX – including Drug-Drug Interactions, metabolism, Hepatoxicity, hepatic clearance,
Clinical Trial Assay – Including GCLP Assay Development, Clinical Sample Analyses

BioIVT’s clinical specimens now include the ASTERAND Human Tissue Specimens, an invaluable source of high-quality, thoroughly characterized and validated human tissue, which can be used throughout the drug discovery and development process. As the leading provider of high quality human biospecimens and associated clinical information, we use rigorous criteria for the procurement and quality control of biospecimens. BioIVT has a worldwide network of hospitals working exclusively to procure high-quality biological samples for our onsite tissue bank. Our dynamic network of hospital procurement sites makes BioIVT unique in the biobanking industry and allows BioIVT to offer our clients many hard to procure treatment naïve tissue specimens in several formats.

Our extensive repository consists of over 300,000 human tissues with associated biofluids. This bank includes material that is prospectively obtained in a variety of formats including fresh frozen and FFPE as well as biofluids. Standard protocols are used to maintain the BioIVT repository and adhere to the highest standards of sample integrity, including difficult to procure treatment naïve tumor samples. Standard tissue products are generally available for next day shipping to keep your research moving.

Our custom procurement service offers human tissues and clinical data custom collected to meet unique research requirements within a wide range of disease categories. Samples are provided in multiple preserved formats or as fresh and unpreserved biospecimens. As a result, we deliver human tissues, biofluids, and accompanying clinical information in a manner that is most compatible with our client’s experimental design.

BioIVT collects every sample under IRB approved protocols, ensuring that strict ethical guidelines are followed to protect patient confidentiality and safety. Each sample has the patients consent for use in a wide range of research including the development of commercial products or services. The samples are identifiable only by barcodes to ensure an unbiased assessment as well as patient confidentiality.

BioIVT provides a complete team of Histotechnicians, Histotechnologists and Board Certified Pathologists for all your sectioning, cyro-sectioning, staining and analysis needs.

PATHOLOGY SERVICES
Standard Services

• H&E with diagnosis confirmation
  Custom Services
• Gross preperation of fresh specimens
• Identification of key tissue features
• Specimen marking
  Platforms & Fees
• Aperio AT2 Slide Scanner
• Fees based on hourly rate

Our team of scientists offer routine DNA (genomic DNA) isolation from flash frozen tissue, FFPE and cells. We also provide mutation analysis on several of our products as well as a custom service.

Standard protocols can be used to obtain genomic DNA. A wide range of commercially available DNA extraction kits or custom protocols can be utilized to obtain samples for specific projects. DNA quality is analyzed by gel electrophoresis. Quantitation it performed by spectrophotometry (Nanodrop) and fluorometry (Qubit). Careful qualitative and quantitative analysis will guarantee high quality specimens and yield high quality research results.

BioIVT offers mutation services to support assay, diagnostic and drug development needs as well as assay validation. We are able to combine ready access to large cohorts of human tissues with expertise in the design and execution of NGS, qRT-PCR and FISH protocols. We can support the determination of SNVs (single nucleotide variants), Indels (Insertion or deletion of nucleotides), Fusions, and CNV (Copy Number Variants) as well as expression changes. qRT-PCR is an effective approach for determining the status of various somatic mutations in human tissue samples. These data aid in the selection of specific subsets of human tissue samples for future use / applications. We have provided such pre-screening services to enable tissue selections for KRAS and EGFR, among other mutations. Using FISH, we generate data that enable characterization of tissues for specific mutations such as HER2 or cMET gene amplifications or ROS/ALK gene rearrangements.
Features & Benefits

• Fully managed by in-house specialist
• Supported by large banked tissue specimen inventory with access to specific cohorts as needed
  Access to multiple platforms:
• qPCR – SNV, Fusion, Expression changes – Tests specific known variants; confirmation of assays
• Sanger/Pyrosequencing – SNV – Test sections of genes or short genes, confirmation of assays
• NGS – SNV, CNV, Fusion – Explore large sections of genome, detection from multiple genes, detection of rare variants, information from multiple mutation types in one assay.

Our BioIVT PHASEZERO® scientists has established expertise in the isolation and culture of human primary cells and in the development of human primary cell-based assays (both 2D and 3D) to support late lead optimization/candidate selection stage compound evaluation. Non-human tissues and cultured cells and human recombinant cell lines are used effectively for screening and the initial identification of compounds with desired pharmacological effects. Moreover, using human tissues and primary cells ultimately provides translational data to support the selection of those compounds with the best opportunity for success in the clinic.

Human Tissue Types
Our core cell-based assay disease areas are inflammation, respiratory and metabolic, with development of 2D and 3D cell culture models ongoing in oncology and fibrosis.

Additional examples of primary cells that have been isolated for custom projects include:

• Blood – PBMC, monocytes, lymphocytes and neutrophils
• Skin – Keratinocytes, fibroblasts
• Lung – Alveolar macrophages, alveolar type II cells, smooth muscle cells, tumor epithelial cells, cancer-associated fibroblasts
• Kidney – Proximal tubule cells
• Breast – Tumor epithelial cells, cancer-associated fibroblasts
• Colon – Tumor epithelial cells, cancer-associated fibroblasts

Features & Benefits
Ability to isolate primary cells from a variety of tissue types and representative diseases 2D and 3D models available culture formats include:

• 2D-Multiwell (6-96 well format)
• 2D-Transwells
• 3D-Spheroid (with or without soft matrix)
• 3D-Air-liquid interface (ALI)
• 3D-OrganDOT™ matrix free aggregates
• 3D-Raft™ physiological density matrix

BioIVT provides a complete team of Histotechnicians, Histotechnologists and Board Certified Pathologists for all your sectioning, cyro-sectioning, staining and analysis needs.

HISTOLOGY SERVICES
Standard Services

• Sectioning
• IHC Staining

Custom Services

• IHC/Custom Staining
• Instrumentation Validation
• Assay Controls
• Specimen Embedding
• TMA Creation

Platforms

• Dako Autostainers
• Aperio AT2 Slide Scanner
• Auto Tissue Processors

PATHOLOGY SERVICES

• Standard Services
• H&E with diagnosis confirmation

CUSTOM SERVICES

• Gross preperation of fresh specimens
• Identification of key tissue features
• Specimen marking

Platforms & Fees

• Aperio AT2 Slide Scanner
• Fees based on hourly rate

We offer primary isolated cells from oncology and other diseased populations, useful in assay development and the identification of diagnostic and prognostic markers. In addition, we offer specific oncology related cell lines.
• Complete clinical data included with all samples
• Customizable PBMC collections for specific inclusion criteria
• Additional characterization available, including HLA typing

BioIVT is your partner for both biologicals and services related to biomarker research. With the expertise required for the ethical acquisition of biospecimens that cover a wide range of disease states and the protocols needed for the production of reliable data, we are able to serve you with the tissues and biofluids you need from the donor cohorts you desire. Whether you need an effective approach for determining the status of various somatic mutations, hotspot variants, copy number variations or fusions in human tissue samples or a ready-banked inventory of prescreened specimens, we have your solution. With the ability to multiplex IHC and /or ISH in the same tissue section, we can expand your capabilities to visualize target and effectors in the same spatial region.
We are able to combine the immediate access to large collections of human biospecimens with expertise in the design and execution of the following :
HLA-genotyping
qPCR
Sanger/Pyrosequencing
Next Generation Sequencing (NGS)
IHC
FISH
Multiplex IHC
Multiplex ISH
Multiplex IHC/ISH

BioIVT’s selection of immortalized cell lines will further your research in the mechanisms of cancer growth and progression. Our cell lines derive directly from freshly isolated solid tumors, including breast and prostate tissues as well as hematological samples. Each cell line purchased includes clinical data delivered with the cell aliquots. Our stringent quality control processes requires authentication including sterility testing, viability, and plating efficiency determined by lot. Immortalized cell lines are cryopreserved in 1 x 106 ampules.
Breast Cell Lines
Through licensing agreements with the University of Michigan and the Karmanos Cancer Institute, BioIVT provides 11 well-characterized human breast cancer cell lines to assist in breast cancer research.
Ten SUM cell lines derived in Steve Ethier’s lab while present at the University of Michigan are available for purchase. Each cell line, from a single patient, represents a different subtype of breast cancer. All of the currently known oncogenes with altered expression patterns in breast cancer, in various combinations, are represented and characterized in the SUM lines. Furthermore, these cell lines have been described in over 50 peer-reviewed publications, describing isolation and growth conditions, gene expression data via Affymetrix GeneChips, and biomolecular markers, such as estrogen receptor and Her2 status.
Prostate Cell Lines **
BioIVT offers three pairs of prostate tumor and normal cell lines. Researchers at the Karmanos Cancer Institute, Onyvax Ltd., and Asterand collaborated to derive these cell lines from tumors and adjacent “normal” tissues obtained at the time of prostatectomy. These prostate cell lines were immortalized via replication-defective retrovirus transferring the transforming HPV16 or HPV18 E6 and E7 genes.
**All prostate cell lines were immortalized were by exposing the cells to a replication-defective retrovirus transferring the transforming HPV16 or HPV18 E6 and E7 genes.
Hematopoietic Malignancies Cell Lines
Through a licensing agreement with the Barbara Ann Karmanos Cancer Institute, BioIVT provides well characterized human cell lines derived from patients with hematopoetic malignancies. These cell lines, developed by Doctors Ayad Al-Katib and Ramzi Mohammad, will be of interest to researchers seeking a cure for lymphoma, leukemia, pancreatic cancer, and macroglobulinema.

The PHASEZERO® Research Services team delivers high quality molecular pathology data to support the selection and validation of drug targets and biomarkers in human tissues. In addition, the approaches we provide are ideally suited for diagnostic assay development and testing. Our molecular pathology platforms are used to great effect as endpoints for our human primary cell based assays. This allows changes in the expression of key targets to be determined following treatment of human cells with novel therapeutic agents.

Key offerings:
Immunohistochemistry
Flow Cytometry
Multiplex Immunohistochemistry

Our BioIVT PHASEZERO® scientists has established expertise in the isolation and culture of human primary cells and in the development of human primary cell-based assays (both 2D and 3D) to support late lead optimization/candidate selection stage compound evaluation. Non-human tissues and cultured cells and human recombinant cell lines are used effectively for screening and the initial identification of compounds with desired pharmacological effects. Moreover, using human tissues and primary cells ultimately provides translational data to support the selection of those compounds with the best opportunity for success in the clinic.

Human Tissue Type
Our core cell-based assay disease areas are inflammation, respiratory and metabolic, with development of 2D and 3D cell culture models ongoing in oncology and fibrosis.

Additional examples of primary cells that have been isolated for custom projects include:
-Blood – PBMC, monocytes, lymphocytes and neutrophils
-Skin – Keratinocytes, fibroblasts
-Lung – Alveolar macrophages, alveolar type II cells, smooth muscle cells, tumor epithelial cells, cancer-associated fibroblasts
-Kidney – Proximal tubule cells
-Breast – Tumor epithelial cells, cancer-associated fibroblasts
-Colon – Tumor epithelial cells, cancer-associated fibroblasts

Features & Benefits
Ability to isolate primary cells from a variety of tissue types and representative diseases 2D and 3D models available Culture Formats include:
-2D-Multiwell (6-96 well format)
-2D-Transwells
-3D-Spheroid (with or without soft matrix)
-3D-Air-liquid interface (ALI)
-3D-OrganDOT™ matrix free aggregates
-3D-Raft™ physiological density matrix

Mammalian Cell Culture Services