Invicro’s Advanced Pathology Services multidisciplinary team provides end-to-end discovery, translational research and clinical trial pathology services for pharmaceutical and biotechnology partners. We support studies across many therapeutic areas,  including oncology, immuno-oncology, neurology, immunology and systemic diseases. Our unparalleled scientific expertise coupled with our operational capabilities allows us to support a variety of project types.

For all projects processed in our laboratory, our dedicated scientific and project management teams collaborate closely with sponsors to design studies that will deliver the insights needed to support research efforts at all stages of discovery and development. When partnering with Invicro, we ensure both sides are aligned on expectations and provide the highest level of transparency expected from a contract research partner.

Discovery Research

• Receptor binding assays
• Image analysis

Translational & Clinical Research 

• Assay design, development and validation
• Routine & specialty stains
• Immunohistochemistry (IHC) / Immunofluorescence (IF)
• RNAScope®, BaseScope™ and miRNAScope™ ISH
• Whole Slide Imaging (WSI)
• Image analysis and reporting
• Pathologist consultation and immunostaining interpretation
• Non-GLP Tissue Cross-Reactivity (TCR) assays
• 510(k) tissue-based submission tests for medical devices
• Regulatory filing support
• Companion Diagnostic (CDx) development for IHC and RNAScope® ISH
• Quanticell™ High sensitivity IHC

Download our translational tissue biomarker services flyer here!

Spatial Proteomics

Akoya Biosciences

Invicro is a qualified CRO service provider of Akoya Biosciences® spatial proteomic solutions. Akoya’s technology analyzes intracellular and extracellular proteins on formalin-fixed, paraffin-embedded (FFPE) tissue sections, enabling protein-based single-cell analysis of tissue architecture. Fresh frozen tissue section solutions are also available.

Invicro is the only qualified CRO service provider to offer both the Phenocycler®-Fusion System for high-plex assays and the PhenoImager® HT for high volume experiments.

Invicro is developing a custom spatial biology image analysis pipeline using many of Invicro’s internal capabilities including VisioPharm®, R Studio, and Akoya’s inForm® for visualizing and quantifying biomarkers in tissue sections. Typical outputs will include cell phenotypes, cellular neighborhoods and clustering maps.

We partner with each client to generate data insights geared to specific research initiatives. All images are shared via through our secure File Transfer Protocol (FTP) service and are fully compatible with open-source viewers such as QuPath or free viewers such as OlyVIA from Olympus.

Ultivue

Invicro is a proud provider of Ultivue assays which offer spatial proteomic insights for profiling cancer biology. Ultivue’s proprietary InSituPlex® technology analyzes intracellular and extracellular proteins, is compatible with FFPE sections, and enables multiplexed insights into the tumor microenvironment. We offer the following Ultivue assays:

Invicro utilizes Visiopharm® and custom scripts to produce cell segmentation and cell phenotyping outputs to provide data insights for each client’s research questions. All spatial biology images are shared through our secure FTP service and are fully compatible with open-source viewers such as QuPath or free viewers such as OlyVIA from Olympus.

Spatial Transcriptomics

10x Genomics – Coming April 2023

Invicro is expanding our spatial biology capabilities with the upcoming service launch of Visium Spatial Gene Expression from 10X Genomics. Explore cell types, states and biomarkers in a morphological context with the ability to map total single-cell RNA sequencing data to the tissue microenvironment in both FFPE and fresh frozen tissue.

Immunohistochemistry (IHC) is a powerful tissue-based method used both in research and clinical diagnostics to evaluate pathological conditions. IHC allows for the visualization of target antigens on the cellular and subcellular level with tissue morphology preserved in a wide-range of sample types, such as solid tumor biopsies, lymph nodes and other isolated tissues. In clinical practice and drug development, IHC is widely used as a companion diagnostic test to stratify patients and monitor the efficacy of therapeutic treatments. With rapid advancements made in the field of immunotherapy, IHC remains a valuable assay to support the development and approval of cutting-edge therapies.

Our laboratories possess the scientific, regulatory and operational expertise to develop and run immunohistochemistry (IHC) assays across multiple therapeutic areas. From early-stage discovery to exploratory endpoint testing and CDx development, our team is prepared to support all your project needs to expedite drug discovery and development efforts. We perform IHC on xenograft tumor models, tissue microarrays (TMA), and a diverse population of human and non-human tissue samples. It is our mission to provide biomarker insights needed to help you make smart decisions that will accelerate drug development efforts.

With multiple laboratory locations and CAP-accredited CLIA-certified sites, we offer comprehensive IHC services to support projects with varying levels of complexity. Our laboratories are equipped with the latest research and clinical tissue processing equipment from Leica, Agilent Dako, Biocare Medical and Ventana to support your specific project needs.

Core Service Capabilities

• Scientific consultation
• Tissue processing & embedding
• FFPE/fresh frozen serial sectioning
• Custom assay development
• CAP/CLIA assay validation
• Singleplex, multiplex IHC
• Multiplex IHC combined with RNAScope® ISH
• Whole slide imaging (WSI)
• Pathologist interpretation
• Non-GLP Tissue Cross-Reactivity (TCR) assays
• 510(k) tissue-based submission tests for medical devices

DOWNLOAD IHC BIOMARKER LIST

Multiplex Immunostain Examples

Immunofluorescence (IF) is a powerful approach to detect and visualize multiple (e.g., 4-plex, 8-plex) biomarkers while preserving tissue morphology to understand spatial relationships. Multiplex Immunofluorescence is an effective approach to examine the colocalization of infiltrating immune cells within the tissue microenvironment, which is particularly important in immuno-oncology drug development.

Developing multiplex immunofluorescent assays and analyzing the data is a challenging process that requires domain knowledge and expertise. Invicro’s team of scientific experts provide a consultative approach to study design, execution, analysis, and reporting. Our approach starts with understanding the question that needs to be answered followed by designing a study that will deliver new insights required to support translational research. We are a platform agnostic solutions provider and can develop new assays using a wide-range of staining chemistries, including tyramide signal amplification (TSA)-based Akoya Opal sequential staining, DNA barcoding-based Ultivue InSituPlex, Ventana multiplex panels, and others. All staining workflows can be developed on automated platforms, including the Leica Biosystems BOND RX or the Ventana DISCOVRY ULTRA.

Core Service Capabilities 

• Scientific consultation
• Study design
• Tissue processing & embedding
• FFPE serial sectioning
• Antibody optimization (e.g., monoplex chromogenic/fluorescent optimization)
• Assay detection optimization
• Multiplex IF combined with RNAScope® ISH
• Multispectral imaging
• Image analysis
• Reporting

Invicro’s dedicated image analysis team provide end-to-end digital pathology capabilities to support all drug research and development phases from biomarker discovery to clinical trials. By partnering with us, we provide research services with rapid turnaround times (TATs) to help uncover biological insights to advance your scientific research. We deploy state-of-the-art analysis workflows to identify phenotypes within the tissue context. In addition to providing combined tissue processing and analysis, we accept digitized slides for analysis only projects to provide clients access to tailored project solutions. To digitize slides for analysis applications, our laboratories are equipped with a broad portfolio of commercial, state-of-the-art systems and image analysis tools.

By combing cutting-edge technologies and software, including Visiopharm and other in-house custom developed tools to meet your specific needs, with our deep expertise in data analytics, we deliver solutions that support brightfield and multispectral fluorescent imaging techniques used to detect biomarkers and phenotype immune cells in the tumor microenvironment (TME). We help clients solve complex research studies by offering analysis solutions for all testing methods, including core histology, multiplex IHC/IF and Quanticell–Konica Minolta’s proprietary high sensitivity, quantitative IHC assay.

Core Analysis Services

• Tumor scoring
• Immune cell counting
• Multiplex stain quantification
• RNAScope® BaseScope™ and miRNA™ ISH analysis
• Multiplex IHC combined with ISH to visualize gene and protein targets
• Morphological analysis
• Custom application development/transfer

In addition to our routine immunohistochemistry and novel quantitative biomarker imaging solutions, Invicro provides multiple specialty stains to support your research efforts across multiple disease areas.    

In addition to our translational biomarker services, Invicro provides clinical pathology services to support clinical trial and companion diagnostic (CDx) development programs. Our CAP-accredited and CLIA-certified laboratory possess the operational experience to optimize and validate biomarker assays, including CAP-CLIA validations and analytical validations needed for FDA submissions. We have established processes to ensure our laboratory remains fully compliant with all regulatory requirements for clinical studies.

Sample Acquisition

• Inspect sample quality and accession into LIMS system for sample chain of custody

Sample Preparation

• Fix, process, section FFPE or fresh frozen tissues

Custom Assay Development / Assay Transfer

• Source and optimize commercially available or sponsor’s proprietary antibodies, identify control tissues and/or cell lines, identify isotype controls, optimize antigen retrieval conditions, select commercial staining platform

Stain Tissue Sections

• Stain primary tissues/tissue microarrays (TMA) using pre-optimized assay conditions and controls

Whole Slide Imaging (WSI)

• Scan slides at 20X or 40X to digitize slide (generate svs files) for image transfer or image analysis

Interpretation and Scoring

• Board-certified pathologist (MD) review, including qualitative review, establishing cutoffs, and IHC scoring

Image Analysis

• Segmentation, morphological assessment, cell counting, distribution analysis, multiplex stain analysis using in-house tools and of the shelf software, including Visiopharm and other custom developed tools

Reporting

• Deliver final report to sponsor, including methodologies utilized, complete analytical study results, statistical analyses

Data Management

• Collate pathology image data using iPACS®–Invicro’s flagship data management platform to streamline data accessibility

Quanticell is advanced and highly sensitive immunohistochemistry-based technology that accurately detects and quantitates specific target antigens at the molecular level supporting drug discovery and development. This quantitative immunohistochemistry assay uses novel fluorescent phosphor-integrated dots (PIDs) and provides superior sensitivity and uniformity compared to conventional immunofluorescent imaging and immunohistochemical methods. PIDs are organic fluorophore assembly-conjugated nanoparticles with unique properties including: uniform size, high intensity fluorescent signal, high photostability (densely packed fluorophores networked via chemical binding), high sensitivity, and broad dynamic range. At Invicro, our image analysis team uses the latest artificial Intelligence-based capabilities to analyze tissues stained with this innovative technology.

To overcome specific detection-related challenges, this assay offers higher sensitivity compared to common chromogenic and fluorescent-based detection methods. This service enables sponsors to:

• Visualize and quantitate low expressing targets and immune cells
• Evaluate and measure drug distribution alongside the drug target
• Monitor and quantify drug pharmacodynamic effects in the tissue context
• Assess and predict drug response in patient tissues

Advantages

• Versatile: Track and measure localization of therapeutics: monoclonal antibodies, antibody-drug conjugates, bispecifics and recombinant proteins
• Sensitive: Detect and quantify low expressing targets while maintaining tissue morphology
• Predictive: Assess drug mechanism of action to build more reliable therapy response models
• Accurate: Reduce detection of false negatives
• Flexible: Compatible with typical FFPE IHC antibodies and multiplex staining methods in a single tissue section

Selected Publications

• Guo Z, Tada H, Kitamura N, et al. Automated Quantification of Extranuclear ERα using Phosphor-integrated Dots for Predicting Endocrine Therapy Resistance in HR+/HER2- Breast Cancer. Cancers (Basel). 2019;11(4):526. Published 2019 Apr 12. doi:10.3390/cancers11040526
• Fujisawa T, Tsuta K, Yanagimoto H, et al. Quantitative immunohistochemical assay with novel digital immunostaining for comparisons of PD-L1 antibodies. Mol Clin Oncol. 2019;10(3):391-396. doi:10.3892/mco.2019.1801
• Inamura K, Shigematsu Y, Ninomiya H, et al. CSF1R-Expressing Tumor-Associated Macrophages, Smoking and Survival in Lung Adenocarcinoma: Analyses Using Quantitative Phosphor-Integrated Dot Staining. Cancers (Basel). 2018;10(8):252. Published 2018 Jul 31. doi:10.3390/cancers10080252
• Yamaki S, Yanagimoto H, Tsuta K, Ryota H, Kon M. PD-L1 expression in pancreatic ductal adenocarcinoma is a poor prognostic factor in patients with high CD8+ tumor-infiltrating lymphocytes: highly sensitive detection using phosphor-integrated dot staining. Int J Clin Oncol. 2017;22(4):726–733. doi:10.1007/s10147-017-1112-3
• Gonda K, Watanabe M, Tada H, et al. Quantitative diagnostic imaging of cancer tissues by using phosphor-integrated dots with ultra-high brightness. Sci Rep. 2017;7(1):7509. Published 2017 Aug 8. doi:10.1038/s41598-017-06534-z

Poster Presentations

• Optimization of an ultrasensitive, quantitative immunoassay for detection of CD20 in Non-Hodgkin’s Lymphoma (NHL) FFPE samples. Goel et al. (2020). The Society for Immunotherapy for immunotherapy of Cancer (SITC).
• Quanticell™, a novel histopathology technology for visualization and quantitation of membrane PSMA demonstrated in cell lines and clinical tissue. Dimant et al. (2020). AACR.
• Examining “Her2 Low” patient populations for prediction to Her2-targeting antibody-drug conjugate response in Her2 negative patients using a novel high sensitivity immunohistochemistry assay. Krueger et al. (2020). AACR.

• Evaluating loss of STING/cGAS expression using a novel multiplex immunohistochemistry detection approach. Goel et al. (2019). The Society for Immunotherapy of Cancer (SITC).
• Quantitative measurement of human epidermal growth factor receptor-2 (HER2) protein expression in ‘classical’ and ‘non-classical’ FISH categories: a comparative study. Shen et al. (2018). USCAP.
• Prognostic value of nuclear and non-nuclear estrogen receptor expression by IHC with phosphor-integrated dots in hormone receptor-positive early breast cancer Guo et al. (2018). AACR.

White Papers

• Overcoming Tissue-based Biomarker Detection Challenges with Quanticell™

Service Flyers

• Download the Quanticell service flyer here!
• Download the Quanticell low HER2 tissue testing flyer here!

Invicro has established a strategic alliance with Paige, a leader in clinical-grade artificial intelligence (AI) for diagnostics, drug discovery and biomarker development applications. With this partnership, Invicro now provides biopharmaceutical clients access to world-class digital pathology solutions across a range of disease indications. The computational pathology solutions support efforts spanning from preclinical discovery studies to clinical trials and diagnostic product commercialization.

Paige has produced AI solutions that generalize and phenotype tissue specimens without the need for labor-intensive and subjective annotation-based methods. In addition, access to critical data, such as genomics, treatment information, drug response, and other clinical assessments is available to augment and gather insights from clinical studies. Through this partnership, we address core challenges including:

• Lack of access to curated pathology datasets
• Need for expertise in managing clinical studies
• Access to regulatory expertise

Pharma Service Offerings

• Custom Biomarker Discovery Studies
• Multi-modality Studies
• Clinical Product Development & Commercialization

Resources

• Download the Digital Biomarker service flyer here!
• Download our White Paper: Discovery of novel AI-based digital biomarkers for the development of personalized oncology therapies here!