MI Bioresearch Inc.

At MI Bioresearch, we offer over 30 different syngeneic tumor models, from both solid and disseminated origins, to provide you with many choices to further your immuno-oncology research and development activities. For many of our models, we have growth curves available, and we continue to build our database with treatment response to agents of interest like anti-CTLA-4, anti-PDL-1, and anti-PD-1 antibodies. In addition, we have access to commercially generated humanized mouse models and can accommodate client-generated models as well.

While rapid screening of test agents can be facilitated by using models in the subcutaneous setting, it is becoming increasingly more important to evaluate the sensitivity of test agents in a setting that is one step closer to a clinical tumor presentation. It is well known within the preclinical research community that the tumor microenvironment can play an important role in the response of tumor cells to therapies. Thus, the context in which the cell resides matters, and discovery research increasingly requires the use of orthotopic and transgenic models in order to provide the greatest confidence in potential clinical effect.

The deep tissue location of the tumors in many orthotopic models makes the assessment of anti-cancer activity difficult without the use of imaging techniques. Traditional methods require the sacrifice of large cohorts of animals, at different time points, to track tumor progression, metastatic spread, and response to therapy. Imaging technology advancements allow for the non-invasive, real-time imaging of orthotopic tumors, over time, with greater speed and fewer animals than traditional methods. Imaging technologies can be combined in orthotopic models to track the response of a tumor to therapy at the anatomic, functional, or molecular (mechanism-of-action) levels.

At MI Bioresearch, we work closely with you to determine the most relevant imaging modality for the question you are trying to answer.

We offer highly reproducible orthotopic models for the following tissue types:

• Brain
• Breast
• Colon
• Leukemia
• Liver
• Lung
• Lymphoma
• Myeloma
• Ovarian
• Pancreas
• Prostate
• Renal

MI Bioresearch’s contract flow cytometry service, MI GoFlow™, provides you with an advanced, state-of-the-art analytical flow cytometry resource to support all aspects of your drug development needs. Run your sample generation studies with us or overnight-ship us your preclinical or non-CLIA regulated clinical samples and we’ll take care of the flow cytometry for you.

Our in-house services for sample processing and data acquisition begin immediately after a study is taken down, eliminating the risk of sample degradation.
Our instrumentation includes two Invitrogen™ Attune™ flow cytometers uniquely designed to handle complex tumor-derived samples and acquire data at rates greater than 10,000 cells per second.
We can generate actionable data on rare cell populations such as regulatory T-cells that can comprise only 1-2 percent of total cells.
Both of our Attune™ NxT’s are fully upgraded with four lasers and 16 detection parameters to support complex antibody panels required for in-depth immunophenotyping and functional characterization of heterogeneous samples.
Our instruments are configured with Attune™ Autosampler plate loaders to support both 96- and 384-well plates, allowing for high throughput capture rates.

MI Bioresearch has a Luminex® 100™ System. This system is a flexible analyzer based on the principles of flow cytometry. The system enables you to multiplex (simultaneously measure) up to 100 analytes in a single microplate well, using very small sample sizes. The system delivers fast and cost-effective bioassay results on many assay formats including nucleic acid assays, receptor-ligand assays, immunoassays, and enzymatic assays. Commercial, pre-made, multiplexed plates are available to measure the components of entire cell signaling pathways or cytokines such as the AKT pathway, apoptosis, chemokines, cytokines, inflammatory cytokines, growth factors, and the TH1/TH2 pathways.

In collaboration with our clients we have performed many successful Western blots against a large number of oncology relevant targets. The staff at MI Bioresearch has extensive experience performing Western blots from multiple sample types such as cultured cells, fresh tissues, and frozen tissues. With the Typhoon Imaging System, chemiluminescent, chemifluorescent, and fluorescent secondary antibodies can be detected allowing for the identification of multiple proteins of interest at one time. MI Bioresearch also has the ability to quantify the bands on a membrane with ImageQuant software to determine the size and relative intensity of each band for each sample.

MI Bioresearch has a Synergy 2 plate reader with a red-shifted PMT, a Cytation 3 plate reader containing monochromators that can measure a wide range of wavelengths, and a 405LS Microplate Washer to reduce incomplete or uneven washing. The staff at MI Bioresearch has extensive experience using ELISAs from multiple vendors and with multiple sample types such as cultured cells, whole blood, fresh tissues, and frozen tissues. Absorbance-based or fluorescence-based ELISA kits can be used to produce a standard curve and accurately quantify the amount of a specific protein in your samples. To obtain the most accurate results, MI Bioresearch routinely generates standard curves from protein standards in duplicate or triplicate and quantitates your protein of interest in each sample from triplicate wells.

We offer comprehensive study design for high-throughput, cost-efficient optical imaging across multiple therapeutic areas. We were the first Xenogen-licensed CRO and have over a decade of experience in designing, executing, analyzing, and reporting bioluminescence studies. Optical imaging protocols and respective models have been optimized for maximum reproducibility and quality.

Bioluminescence imaging (BLI) relies on detection of light from luciferase-expressing cells in an animal. This is commonly achieved through implantation of cells engineered to express luciferase constitutively or by use of transgenic animals that express luciferase in one or more tissues of interest. Emission of light from these cells or tissues occurs following systemic injection of the luciferase substrate, luciferin.

We utilize optical imaging and a large panel of luciferase-expressing tumor cell lines for tracking tumor burden in orthotopic, disseminated, and metastasis tumor models. MI Bioresearch has the capability to engineer our in-house cell lines or your personal cell lines to express luciferase for BLI detection.

Preclinical Single Photon Emission Computed Tomography (SPECT) is a flexible and quantitative method for determining biologics biodistribution, kinetics, and targeting. Our SPECT imaging platform allows you to assess early biologic candidates to make better decisions with greater confidence.

SPECT is a 3D nuclear medicine imaging technique that provides qualitative and quantitative physiologic measurements. Detection of a SPECT isotope occurs using gamma detectors, with the detection events being used to tomographically reconstruct a three-dimensional image of the isotope molecule distribution in the whole body.

Key advantages of SPECT imaging:

• Non-invasive imaging of fine kinetics can be examined allowing establishment of a kinetic curve by tissue or even by tissue compartment (heterogeneity)
• Full 3-dimensionality of biodistribution with tissue localization aided by anatomical CT overlay
• Clinical translational
• Tracer multiplexing—multiple isotopes of different energies can be used to address multiple simultaneous questions in the same subjects

Our micro computed tomography (CT) imaging platform draws on our expertise in implementing, developing, optimizing, and validating micro-CT imaging paradigms for drug research studies. Our experience in CT-based bone and soft tissue imaging encompasses a number of disease states.

In vivo micro-CT imaging enables high-resolution (to ~50 microns), three-dimensional image generation by rotation of an x-ray source and detector around an imaging subject. Multiple projections are obtained during the rotation and reconstructed to generate the three-dimensional image. The large density differences between bone, soft tissue, and air make them readily distinguished by CT. CT contrast between different soft tissues is generally more subtle. The use of systemically administered, CT contrast agents enables better visualization of the soft tissues, including the vascular system.

Our staff has implemented, validated, and optimized discovery MRI applications since 2003. Today we offer a wide range of in vivo MRI applications using our 7T small animal MRI system.

Magnetic resonance imaging (MRI) is based on the phenomenon of nuclear magnetic resonance (NMR). Since the magnetic resonance properties of nuclei such as hydrogen nuclei (or protons) in water are affected by a variety of physiological parameters, MRI can be used to spatially encode a variety of tissue properties including water content, cellular density, iron content, oxygenation, metabolite concentration, and elasticity.

Additionally, MRI probes such as gadolinium-, iron oxide-, manganese-, nitrous oxide-, and 19-fluorine-containing molecules can be used to further interrogate disease states. Probe use can be leveraged to improve diagnostic sensitivity or to provide unique biomarkers for properties including blood flow, blood volume, and tissue perfusion.

While MRI is one of the most flexible imaging modalities, it has relatively low sensitivity, which limits throughput compared to other established imaging modalities. Years of experience have honed our staff’s ability to overcome the challenge of maintaining quality, while driving MRI throughput, to make powerful, industry-relevant MRI studies feasible.

MI Bioresearch has two Attune NxT flow cytometers with four lasers capable of detecting fluorescent compounds in 14 channels. Whether you need to examine the abundance of a specific protein or multiple proteins on the surface or inside cells, our flow cytometry experts together with the Attune NxT can make it happen. Monitor the abundance or localization to/from the plasma membrane of a specific protein over time with treatment or compare the levels of a protein in different cell lines or mouse strains. Combine the detection of a specific protein with any of our other common flow cytometry cell process assays, (below) such as the apoptosis, cell cycle, or cell viability assay to determine if the abundance of the protein changes at different stages of a cell process. We have successfully detected hundreds of different proteins in samples such as cultured cells, blood, tissues, and organs. In blood, we have successfully detected proteins using a no-wash no-lyse assay which reduces the amount of manipulation and allows the analysis of very small volumes of blood. Find out more about our Flow Cytometry services on our MI GoFlow™ – Advancing Your Flow Cytometry page.

Analyze your tissue samples with IHC staining to detect abnormal cells such as those found in cancerous tumors. Specific molecular markers are characteristic of particular cellular events such as proliferation or cell death (apoptosis). IHC is also widely used in basic research to understand the distribution and localization of biomarkers and differentially expressed proteins in different parts of a biological tissue. MI Bioresearch offers a full suite of in-house histology and IHC services including custom work, and will be adding markers routinely. Our services include:

• Panels: Cancer, Immuno-Oncology
• Normal Tissue, Tumor, Xenograft, Cell Line, Validation, Immunofluorescence, Immunocytochemistry, Multiplex, FISH/ISH

ADME and DMPK Studies Services

Pharmacology & Toxicology Services

Oncology Animal Models Services

Animal Models of Disease Services

Biomarkers Services

PCR Services

DNA Services

Nucleic Acid Services

Bioanalysis Services

Protein Quantification Services

Protein Purification and Quantification Services

Cell and Tissue Culture Services

Cytotoxicity Assays Services

Toxicology Services

Clinical Imaging Services

Radiography Services

Imaging & Spectroscopy Services

Animal Imaging Services

Animal Model in vivo Analyses Services

Animal Models and Studies Services

Cytometry Services

Cells and Tissues Services

Clinical and Anatomic Pathology Services

Clinical Laboratory Services

Immunostaining Services

Protein Expression Visualization Services

Protein Services

Biochemistry & Molecular Biology Services

Biology Services