ADSORB | Bioaster

Aim/Technological Description

Traditional biofilm models for antimicrobial screening are limited in their ability to recapitulate human structures and functions. In vitro biofilm models are essential in research laboratories for testing new antibiofilm compounds, as well as in clinical laboratories for determining the optimal treatment of biofilm- related infections.

The technology, named ADSORB, is a smart and versatile hydrogel-based microfluidic platform for controlled biofilm formation and analysis. Mimicking biofilm biology, this platform will ensure better characterization, analysis of biofilm and easily adapt to diverse pathologies. This new models will diminish the gap between in vitro and in vivo settings. Finally, the microfluidic platform will be used as a preclinical screening system to validate the anti-biofilm activity of novel drugs.

Background

The high rate of failure during clinical phases of antimicrobial development in infectious disease, has led the scientific community to implement pre-clinical in vitro methods, especially those that allow the control of a 3D microenvironment such as organoids and tissue-on-chip.
The in vitro formation of a biofilm is known to be strongly dependent on substrate properties, especially on biotic surfaces, including host receptors and mechanical properties. The adsorption of (macro)molecules on the substrate, also known as conditioning film, changes the physicochemical properties of the surface and affects the bacterial adhesion. Previously, the use of hydrogels have been used as a biotic substratum for culturing biofilms but in practice the substrate was not engineered to improve cell attachment. Efforts have also devoted to develop microfluidic systems to mimic the dynamic environment, performing more realistic in vitro assays. However, these closed systems do not simulate the specific interaction with host receptor. In addition, most microfluidic in vitro models are poorly representative because in vivo biofilms are not exposed to a continuous flow of fresh media. Finally, previously developed dynamic systems are limited in terms of off-chip analysis: closed circuits do not give access to the biofilm in a simple way.

Evidence / Results

a novel on chip technological method (one step protocol) to integrate a hydrogel as diffusive membrane
a three parallel microchannel device was designed, fabricated and tested
static and dynamic diffusion of a fluorescent dye was demonstrated without biofilm
the different distance of the lateral microchannels could be used to deliver drugs of interest with a sequentially and timely controlled d administration
a biofilm with Staphylococcus aureus, as preliminary test, was formed onto the novel chip and characterized by confocal microscopy

Advantages

Integrated and modular microfluidic system allowing

engineering of microchannel surface for improved capability in biofilm formation,
use of reduced quantity of reagents,
perfusion-diffusion based exchange of the nutrients/drugs at high resolution,
applicable for antimicrobials/antibiofilms development, and
applicable for in-depth analysis on persister cells or residual biofilm after drug treatment.

The Adsorb platform associated to bacteria causing biofilm associated diseases has unique advantages for in vitro cell-based assay and antimicrobials development, because of the flexibility and versatile of the method. It allows :

a high quality of first biofilm layer controlling the stronger adhesion to the surface through molecular-specific interactions (closer to in vivo models).

Potential Applications

More than 80% of human chronic infections are associated with biofilm. Biofilm infections are difficult to treat due to the complexity of the structure and a reduced susceptibility to most antibiotic. Moreover, bacteria living in the biofilm exhibit different physiology than in the planktonic phase. It is necessary to identify novel molecules to fight biofilm infections.

The integrated perfusion-diffusion based culture will generate new protocols for in vitro tests of antimicrobials, and thus pave the way for the development of innovative therapeutic strategies.

Outlook

Based on its existing platform, BIOASTER is interested in partnering with companies willing to benefit of the potential of the technology or to collaborate on the development of the platform itself:
Comparison between the biofilm formed in commercially available platform (ibidi μSlide or Biolfux) and ADSORB chip.
Expand the scope to other target pathogens by culturing other pathogens (i.e. ESKAPE pathogens such as Pseudomonas Aeruginosa) and characterization of the biofilm Create stand-alone units with potential diagnostic or laboratory equipment manufacturers.
Combine the technology with other phenotypic screening technologies develop by partners or existing within BIOASTER.