organ-Chip model

Liver-Chip

Confidently predict drug safety and rapidly iterate on AAV design for preclinical drug candidates.

Liver‑Chip Overview

The quad-culture Emulate human Liver-Chip combines four human cell types in a dynamic microenvironment to support in vivo-like gene expression, functionality, and physiology. Validated applications include general and mechanistic toxicity evaluation as well as assessment of AAV-based gene therapy transduction efficiency and safety. 

A diagram showing a cross-section of the Emulate Liver-Chip, with hepatocytes in the top channel, and endothelial cells, Kupffer cells, and Stellate cells in the bottom channel.
Schematic of the quad-culture Emulate human Liver-Chip

Characterization

A validated and comprehensive preclinical human liver model

The Emulate human Liver-Chip faithfully recapitulates in vivo physiological functions of the human liver through critical microenvironment features such as 3D multicellular architecture and vascular flow. These features enable the Emulate human Liver-Chip to provide a more human-relevant model of the liver compared to conventional sandwich cultures, spheroids, and animal models, each of which lack relevant features to appropriately model the human liver.

Category

Feature

Liver-Chip

Sandwich Cultures

Spheroids

Animal Models

Human Relevance

Human Cells

Yes

Yes

Yes

No

Physiologically Relevant
Biomarkers & Morphology

+++

+

+

++

Accurate Prediction of
Human Hepatotoxicity

+++

-

++

+

Microenvironment
Complexity

Multi-cellular Complexity

++

+

+

+++

Vascular / Media Flow

Yes

No

No

Yes

Tissue-specific ECM

Yes

No

No

Yes

Experimental Design

Tunable Dosing Parameters

++

++

++

+

Duration of Experiment

++

-

++

+++

Clinically Relevant Assays

+++

+

+

++

Convenience

Speed to Insight

++

+++

+++

+

Ease of Learning Curve

++

+++

+++

+

Cost-effectiveness

++

+++

+++

+

Characterization

A validated and comprehensive preclinical human liver model

The human Liver-Chip faithfully recapitulates in vivo physiological functions of the human liver through critical microenvironment features such as 3D multicellular architecture and vascular flow. These features enable the Liver-Chip to provide a more human-relevant model of the liver compared to conventional sandwich cultures, spheroids, and animal models, each of which lack relevant features to appropriately model the human liver.

Category

Human Relevance

Feature

Human cells

Liver-Chip

Yes

Sandwich Cultures

Yes

Spheroids

Yes

Animal Models

No

Category

Human Relevance

Feature

Physiologically relevant
biomarkers & morphology

Liver-Chip

+++

Sandwich Cultures

+

Spheroids

+

Animal Models

++

Category

Human Relevance

Feature

Accurate prediction of
human hepatotoxicity

Liver-Chip

+++

Sandwich Cultures

-

Spheroids

++

Animal Models

+

Category

Microenvironment Complexity

Feature

Multi-cellular complexity

Liver-Chip

++

Sandwich Cultures

+

Spheroids

+

Animal Models

+++

Category

Microenvironment Complexity

Feature

Vascular/media flow

Liver-Chip

Yes

Sandwich Cultures

No

Spheroids

No

Animal Models

Yes

Category

Microenvironment Complexity

Feature

Tissue-specific ECM

Liver-Chip

Yes

Sandwich Cultures

No

Spheroids

No

Animal Models

Yes

Category

Experimental Design

Feature

Tunable Dosing Parameters

Liver-Chip

++

Sandwich Cultures

++

Spheroids

++

Animal Models

+

Category

Experimental Design

Feature

Duration of Experiment

Liver-Chip

++

Sandwich Cultures

-

Spheroids

++

Animal Models

+++

Category

Experimental Design

Feature

Clinically Relevant Assays

Liver-Chip

+++

Sandwich Cultures

+

Spheroids

+

Animal Models

++

Category

Convenience

Feature

Speed to Insight

Liver-Chip

++

Sandwich Cultures

+++

Spheroids

+++

Animal Models

+

Category

Convenience

Feature

Ease of Learning Curve

Liver-Chip

++

Sandwich Cultures

+++

Spheroids

+++

Animal Models

+

Category

Convenience

Feature

Cost-effectiveness

Liver-Chip

++

Sandwich Cultures

+++

Spheroids

+++

Animal Models

+

Microsopy images of human hepatocytes in the Liver-Chip after  exposure to a toxic compound. Images show a concentration-dependent decrease in mitochondria (yellow) in response to treatment with sitaxsentan.
Concentration-dependent decrease in mitochondria (yellow) in response to treatment with sitaxsentan at 0, 1, 10, and 100 times the unbound human Cmax for 7 days in the Emulate human Liver-Chip.

Hepatotoxicity

RESEARCH CHALLENGE

Drug-induced liver injury remains a primary cause of drug candidate attrition and withdrawal from the market

Current preclinical models inadequately predict hepatotoxicity and DILI in humans. Poor clinical translation arises from species differences present in animal models and the limited in vivo-relevant physiology of conventional liver cell culture. This not only leads to high preclinical and clinical attrition, but it can also pose serious health risks to patients. 

Liver-Chip Benefits

A more predictive in vitro model of human hepatotoxicity

In a landmark study in Communications Medicine, part of Nature Portfolio, researchers demonstrated that the Emulate human Liver-Chip could improve patient safety and reduce small-molecule clinical trial failures due to liver toxicity by up to 87%, with 100% specificity. The Emulate human Liver-Chip enables researchers to assess diverse mechanisms of toxicity with greater fidelity than animal testing or conventional cell culture, lowering the risk of DILI and clinical trial attrition for drug candidates.

A tall, vertical image showing fluorescence microsopy image of adeno-associated virus transduction of hepatocytes in the Liver-Chip.
AAV Transduction of Hepatocytes in the Emulate human Liver-Chip

AAV Transduction

RESEARCH CHALLENGE

Development of safe and efficient gene therapy vectors remains slow

Gene therapy holds enormous promise for inherited and acquired genetic diseases, yet progress remains slow. Developing safe and effective viral vectors is time consuming and challenging. Animal studies are slow, costly, and tightly regulated, while conventional in vitro models’ limited cellular complexity results in non-physiological response. These challenges have led not only to a slow pace of gene therapy approval, but also serious safety risks to patients. 

Liver-Chip Benefits

A faster path to AAV optimization

With the Emulate human Liver-Chip, researchers can test the delivery efficiency and safety of adeno-associated virus (AAV) vectors in a human-relevant model of the liver sinusoid and get results in weeks—not months, like with animal models. With this application, it is possible to rapidly iterate on AAV design and explore each cell type’s contribution, accelerating optimization ahead of clinical trials.

Part of the Human Emulation System

The Human Emulation System is comprised of instruments, consumables, and software in a flexible, open format. The user-friendly platform gives researchers a window into the inner workings of human biology.

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Get Started Today

Experience the predictive power of Organ-on-a-Chip technology. Gain deeper insights by incorporating the Emulate human Liver-Chip in your lab workflow or having our team of scientists design and execute a study to meet your needs.

Bio-Kit

Includes chips, reagents, and pre-qualified human cells.

Services

Standard services and custom collaboration projects available.

Basic Kit

Includes chips and reagents for use with customer cell sourcing.

FEATURED RESOURCE

Publication: Performance assessment and economic analysis of a human Liver-Chip for predictive toxicology

Scientific and economic findings highlight the Emulate human Liver-Chip’s ability to predict drug-induced liver injury with 87% sensitivity and 100% specificity while driving a $3 billion-dollar increase in R&D productivity.