Preclinical CRO

BiCell Scientific Inc offers cutting-edge preclinical contract research organization (CRO) services that are based upon a robust rodent animal testing platform to fulfill applications from lead-compound discovery to advanced therapeutic validation.

Areas of study include, but are not limited to:

Anatomic and clinical pathology

Bioanalytics

CAR-T cell development and validation

General toxicology

Knockout and knockin mouse generation

Metabolic cage studies for rodent

Method development and validation

Safety pharmacology

T cell harvesting and activation

Telemetry measurement of rodent cardiology

Transdermal glomerular filtration rate (GFR) measurement

Routes of Administration:

Intravenous (bolus or continuous infusion)

Intramuscular

Intraperitoneal

Oral

Subcutaneous

Mouse and Rat Protocols:

FACS sorting

Histology and pathology

IHC and ISH

In vivo transfection of DNA or RNA with liposomes

Lentivirus or adenovirus transduction

Real-time PCR analysis

RNA and protein extraction

Tissue collection

Tissue specific DNA/RNA transfection

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BiCellFectamaxVivo transfection of mouse liver and lung

Left panel: molecular components of BiCellFectamaxVivo reagent.

Right panel: validation of GFP expression in the liver and the lung via tail vein injection of GFP expressing plasmid with BiCellFectamaxVivo to 6-week-old mouse.

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Physiologic recording of rodent renal function and cardiac function

Left panel: recording of glomerular filtration rate (GFR) in experimental mouse. MediBeacon's transdermal GFR technology is used to measure the GFR in real-time after an IV injection of fluorescein isothiocyanate-labelled sinistrin.

Right panel: recording of ECG and blood pressure in experimental mouse. DSI's telemetry transmitter is implanted into the carotid artery to measure real-time changes in mouse cardiac functions.

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Lentivirus production and infection of mouse embryo

BiCell Scientific’s lentivirus transgenic mouse generation service provides a complete set of services to make siRNA/microRNA mutant mouse by lentivirus including lentivirus vector synthesis, lentivirus packaging, lentivirus purification, 1-cell stage mouse embryo collection, perivitelline injection to embryo and embryo transfer to pseudopregnant mouse.

Top panel: Lentiviral backbone vector features transgenic expression cassette flanked by 5’-LTR and 3’-LTR. Middle panel: Packaged virions were used to transduce mouse zygote cells for transgenic expression, in this case, GFP expression, and examined at 2-cell, 4-cell, 8-cell and morula stage.

Bottom panel: Transduced mouse zygotes were allowed to develop to term and examined for GFP expression in a variety of tissues.

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BAC/YAC/Plasmid DNA Transgenic Mouse Generation

BiCell Scientific’s BAC/YAC/Plasmid DNA transgenic mouse generation service provides a complete set of services to make transgenic mutant mouse including BAC, YAC or plasmid DNA construct synthesis, 1-cell stage mouse embryo collection, cytoplasmic injection to embryo and embryo transfer to pseudopregnant mouse.

Top panel: Labeling of 1-cell stage mouse embryo.

Bottom panel: (a) Embryo is held by a holding pipet. (b) Injecting pipet penetrates the plasma membrane of the embryo. (c) Injecting pipet is inserted into the male pronucleus. (d) Injecting pipet delivers DNA payload.

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Custom Cell Sorting & Clonal Selection

BiCell Scientific’s Custom Cell Sorting Service provides customized cell sorting and clonal selection for a variety of cell models, including CAR-T cells, TCR-T cells, B cells, ES cells, iPS cells, KO/KI cells and CRISPR cells.

Top panel: GFP positive cells were sorted into singlets and collected into P1 fraction.

Bottom panel: Individual cells from P1 fraction were dispensed into 96-well plate to establish independent clones.

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Establishing subcutaneous or orthotopic xenograft tumor model

Our barrier facility is able to accommodate nude mice or other immunodeficient mouse models from the Jax lab, such as SCID mice, NSG mice and etc. We can perform subcutaneous or orthotopic xenograft to implant tumor cells of customer's choice. Our preclinical therapeutic studies include ADC, bispecific antibodies, CAR-T and more.

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In vivo CAR-T cell Injection & validation

Our preferred infusion route for CAR-T cell therapy is i.v. via tail vein. Our preferred route for blood collection is via retro-orbital sinus. Our CAR-T cells express a co-expression marker of GFP, which can be used for FACS sorting of total cells from whole blood. Injection and validation of human Jurkat negative control CAR-T cell (SP6-scFv-CD28-CD3) are shown here. 

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Typical cost and pricing schedule of animal experiment

We source experimental mice of various mutant strains from the Jax lab. Our experimental and procedural cost and per diet rate can be found in the table below. Our CRO service includes serum collection and tissue collection. Tissues of customer's choice will be fixed with 10% neutral formalin and preserved in paraffin blocks. Additional histopathology services can be found in the link below:

https://bicellscientific.com/product/histopathology-service/

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Rodent workstation with anesthesia system

Our rodent workstation is based upon Allentown's Phantom barrier system and VetEquip's COMPAC5 isoflurane vaporizer system with active scavenging. The COMPAC5 system can supply two independent breathing circuits and one to three independent vented induction chambers.

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Barrier facility for rodent housing

Allentown LLC has custom built a barrier facility for rodent that is capable of handling “nude mouse” as well as performing mouse T cell harvesting and manipulation. The new animal facility has triple layers of HVAC systems and HEPA filters to provide pathogen free environment for animal research.

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