BLOOD-ON-CHIP | Bioaster

Aim/Technological Description

Our technology, named Blood-On-Chip, is aiming at developing a micro physiological system (MPS) with circulating blood cells and a microenvironment mimicking the injection site of a vaccine.

Our microdevice arises from a strong unmet needs to develop innovative preclinical solutions using human cells to predict vaccine immunogenicity and mitigate the risk of preclinical vaccine development. Our development is focused on designing a microdevice reproducing the physiologic situation in human. We will mimic the blood flow by taking advantage of the dynamic environment allowed by organ-on-chip technologies to create a more predictive device as compared to existing static in vitro solutions.
Our micro physiological systemis intended to reproduce the innate immune cells activation following vaccine activation/immune stimulation. Our goal is to build a device that can be used to study existing and new vaccine technologies such as mRNA and novel adjuvants and ultimately decrease the need for animal use.

Background

Our microdevice arises from a strong unmet need to develop innovative preclinical solutions using human cells to predict vaccine immunogenicity and mitigate the risk of preclinical vaccine development.

At the present time there is a big technology gap between in vitro 2D cell culture systems and in vivo and clinical studies.

Our development is focused on designing a microdevice reproducing the physiologic situation in human. We will mimic the blood flow by taking advantage of the dynamic environment allowed by organ-on-chip technologies to create a more predictive device as compared to existing static in vitro solutions.

These developments are still challenging due to complexity of fabrication methods to build a device that can be used to study existing and new vaccine technologies such as mRNA and novel adjuvants and ultimately decrease the need for animal use.

The culture of circulating immune cells with conventional in- vitro methods is today very challenging and cells are apoptotic within hours. Furthermore, static culture systems such as transwell studies, do not recreate the physiological environment sufficiently. Recent development of micro physiological systems represents an alternative to conventional methods to overcome the bottleneck of immune cell maintenance and co-culture.

Evidence / Results

We developed a PDMS-glass microfluidic device that spatially organizes a co- culture consisting of primary human skeletal and endothelial cells mimicking the interface between blood flow and a microtissue. An injectable biodegradable,
a natural hydrogel, is introduced in-between both circulation and microtissue compartments to maintain tissue integrity. To simulate in vivo-like conditions, shear stress can be applied to circulating PBMCs in a physiological range. An ultimate objective is to achieve shear stress up to 30 dyn/cm2..

Advantages

In addition to the advantages of any organ on chip, the technology benefit of the following features:

Being a dynamic system applying shear stress to cells
No pre-requisite according to the adjuvant formulation chemical class

On a more technical point of view the advantage of the technology regarding inflammation in tissue is to

Confine biodegradable hydrogel in microchannel.
Demonstrate the molecular transport of through the hydrogel.
Demonstrate the possibility of Human cell co-culture

Potential Applications

All application where there is a need for better in vitro models and where cells are in motion and in controlled O2 tension may be targeted.

More precisely, application will focus on any research that requires to measure and monitor early time point and innate response.

On a first approach, the technology will be designed to better characterize and classify the molecular determinants of inflammation and its resolution associated with different types of adjuvants. This will pave the way to improve vaccine design and access to personalized vaccinology.

Outlook

Collaboration with owners of adjuvants is thought to enter into the second validation phase using commercial adjuvants to compare RNA Seq data obtained with the technology to already published technologies. Some adjuvants may not be compatible with the Bood-on-Chip device. There may be a design phase depending on demand.
Discussion for a demonstration on clinical sample are currently occurring, and any industrial partner interested to the development of the Blood-On-chip technology main join this demonstration phase.
A second version of the technology will deepen the biological aspect and will integrate lymphoid like organs to take immune response a step further.