Invicro’s Advanced Pathology Services (APS) team provides end-to-end solutions to support translational and clinical research by providing a combination of routine and unique tissue imaging services. As part of Konica Minolta’s broad precision medicine group, we provide a wide-range of tissue biomarker capabilities from assay development through commercialization. Our scientific, operational and regulatory expertise enables us to deliver insights needed to take lead drug candidates to the next level. As an R&D service provider, we offer routine and novel pathology services including: core histology, specialty stains, 3D tissue imaging, Immunohistochemistry (IHC), immunofluorescence (IF), in situ hybridization (ISH) and fluorescent in situ hybridization (FISH) with the option to perform select assays in a CAP-accredited, CLIA-certified laboratory. With laboratory locations in Boston, MA, Irvine, CA, and Tokyo, Japan, we are able to support projects spanning all phases of drug discovery and development.
Invicro’s Advanced Pathology Services multi-disciplinary team provides end-to-end discovery, translational research and clinical trial pathology services for pharmaceutical partners. We support studies across many therapeutic areas including: 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 R&D 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.
- Receptor binding assays
- Cryo-fluorescence tomography (CFT)
- 2D and 3D quantitative autoradiography (ARG)
- Whole-body autoradiography (ARG)
- Micro-autoradiography (MARG)
- Image analysis
Translational & Clinical Research
- Assay design, development and validation
- Routine & specialty stains
- Immunohistochemistry (IHC)
- Quanticell™ High sensitivity IHC
- Custom ISH / FISH assays
- Image analysis and reporting
- Regulatory filing support
- Pathologist consultation and immunostaining interpretation
- IVD reagent development
Quanticell™ High Sensitivity Immunohistochemistry (IHC)
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
- 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
- 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
- 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
- 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.
- Quantitative analysis of ADCs: Whole tumor and intra-tumor PK analysis provides quantitative results on trastuzumab distribution. Matsukane et al. (2017). AACR.
- Download the Quanticell service flyer here!
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 (monkey, rodent, rabbit, dog and cat) 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
- Tissue processing & embedding
- FFPE/Fresh Frozen serial sectioning
- Custom assay development
- Singleplex, multiplex IHC
- Singleplex, multiplex IF
- Whole slide imaging (WSI)
- Pathologist interpretation
Multiplex Immunostain Examples
Cryo-Fluorescence Tomography (CFT)
CFT is an imaging technique performed on whole frozen animals (e.g., rats, mice, etc.) or organs that provides white light anatomical and molecular fluorescence 3D images with micron scale resolution. CFT bridges the gap between fluorescence histology and bulk fluorescence imaging by providing high-resolution imaging of multiple fluorophores simultaneously in a range of sample sizes.
High resolution, large tissue images are captured using sequential section-image cycles. This allows a high-throughput imaging workflow for whole animals or multiple organs (e.g., rodent organ, whole rodent body, dog or monkey head) by embedding multiple samples per block. The 3D mapping of the fluorescent signal is done with anatomical white light and images can be viewed slice-by-slice as a flythrough of the white light and fluorescence images, or via 3D multiplane rendering.
We approach all projects with a data-driven mentality and understand that quality data is critical to solving scientific challenges. Our team is constantly innovating and developing efficient processes to extract meaningful and valuable quantitative information to drive the drug development process forward.
- Evaluate the biodistribution of biological therapies including: oncolytic viruses, monoclonal antibodies (mAb), antibody drug conjugates (ADC) and bispecific fusion proteins
- Track the biodistribution and transduction of gene therapies using different routes of administration
- Track and visualize CAR-T cells, natural killer (NK) cells, dendritic cells, macrophages and stem cells
- Visualize and characterize transgenic and reporter models
- High Sensitivity: Compared to BLI/FLI, CFT offers higher sensitivity to detect signal deep in tissue
- Superior Resolution: Provides highest resolution compared to traditional whole animal imaging modalities
- Increased Throughput: Process several mice or multiple dissected organs on the same block
- Robust: Reduce data variability by combining CFT with in vivo imaging and tissue microscopy from the same animal
- Simple: No fixation, perfusion, tissue clearing, or radiolabeling required to maintain complete anatomical context
- Evaluating delivered gene therapies in vivo to evaluation site of gene transduction
- Determining the Pharmacokinetics (PK) and Pharmacodynamics (PD) of intrathecally administered ASOs
- Detecting spread of metastatic lesions in preclinical animal models using CFT
- Visualizing the renal clearance of two fluorescent-based tracers
- Developing a forward model for CFT imaging simulation
- Mazur C, Powers B, Zasadny K, et al. Brain pharmacology of intrathecal antisense oligonucleotides revealed through multimodal imaging. JCI Insight. 2019;4(20):e129240. Published 2019 Oct 17. doi:10.1172/jci.insight.129240
- Wolf DA, Hesterman JY, Sullivan JM, et al. Dynamic dual-isotope molecular imaging elucidates principles for optimizing intrathecal drug delivery. JCI Insight. 2016;1(2):e85311. Published 2016 Feb 25. doi:10.1172/jci.insight.85311
- Multi-modality imaging study to determine AAV biodistribution compared to AAV transduction in whole animals. Dimant et al. (2019). Gene Therapy for Neurological Disorders Summit.
- Cryo-fluorescence tomography as a new tool in 3D visualization of tumor heterogeneity, metastatic proliferation, and immuno-oncology. Brevard et al. (2018). AACR.
- 3D assessment of antibody distribution within clinical tumors using cryofluorescence tomography. Dimant et al. (2017). WMIC.
- Download the CFT service flyer here!
Autoradiography (ARG) is an imaging technique used to assess the distribution of radiotracers in whole animal (i.e., mice and rats), discrete organs, tissues and cells. Whole body ARG allows for the visualization of drug pharmacokinetics and drug penetration into specific targets during the lead optimization process of drug screening. This imaging modality provides quantitative outputs and can be combined with other high-resolution optical modalities (e.g., bright field for anatomical referencing). In addition, Microautoradiography (MARG) offers higher resolution (0.3 µm) for imaging soft tissue section to evaluate the distribution of radiotracers on the cellular and sub-cellular levels.
- Biodistribution and quantitation of radiotracers
- Build 3D models from 2D Autoradioluminograms to quantify drug distribution in whole organs or animals
- Radioligand binding studies for receptor characterization
- Quantitative whole body autoradiography (QWBA) to determine organ biodistribution
- Quantitative: Quantify multiple classes of small molecule drugs and biological therapeutics
- Sensitive: Detects nanocurie amounts of radiotracer introduced into biological systems
- High Resolution: Delivers highest resolution on the micron scale compared to traditional in vivo imaging modalities
- Medium Throughput: Process multiple whole animal and dissected organs on the same block
- IIovich O, Qutaish M, Hesterman JY, Orcutt K, Hoppin J, Polyak I, Seaman M, Abu-Yousif AO, Cvet D, Bradley DP. Dual-Isotope Cryoimaging Quantitative Autoradiography: Investigating Antibody-Drug Conjugate Distribution and Payload Delivery Through Imaging. J. Nucl Medicine. 2018;59(9): 1461. Published 2018 May 4. doi: 10.2967/jnumed.118.207753.
- Development of a medium-throughput method to screen the effect of test articles on mouse brain activity using 14C-2-deoxyglucose (14C-2DG) 3D autoradiography. Sullivan et al. (2018). NRM.
- Download the ARG service flyer here!
Core Histology & Specialty Stains
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.
|Alcian Blue-PAS-hematoxylin stain||Alkaline Phosphatase stain|
|Aniline Blue stain||Bielschowsky’s silver stain|
|Goldners Trichrome stain||Gomori’s Trichrome stain|
|Luxol fast blue and PAS stain||Masson’s Trichrome stain|
|Methylene blue/basic fuchsin stain||Movat pentachrome stain|
|Periodic acid-methenamine-silver stain (PAM)||Picrosirius red/van gieson picrofuchsins stain|
|Safranin O/fast green stain||Sirius red stain|
|Toluidine blue Stain||TRAP stain|
|TUNEL stain||Von kossa stain|