Development of a novel 3D microfluidic assay platform for the assessment of human stem-cell derived epithelial function.

To solve this problem we will develop a lab-on-a-chip device that can be made from inexpensive plastics and integrates
several laboratory functions on a single chip of less than a square centimetre in size. This user-friendly miniaturised device
will be used to grow lung cells that can be derived in almost limitless supply from adult human stem cells. The cells will be
grown in the chip where they make an epithelial barrier and provide a model for airway tissue with air on one side and liquid
on the other. It also provides constant flow around the tissue and is designed to provide nutrients and remove waste
products as occurs in the body; it also enables small samples of the liquid surrounding the tissue to be collected at different
time points to monitor the behaviour of the epithelial cells. We will also monitor the electrical properties of the epithelial
barrier formed by the lung tissue in the chip so that the effect of environmental triggers can be followed. In this way we will
create a 'Smart biochip' that provides a sustainable and accessible model of the airway epithelial barrier which can be
challenged with environmental triggers (such as house dust, pollen or viruses) and used to investigate the effects of
potential new drug therapies in comparison with established anti-inflammatory therapies such as steroids.
The objectives of the project are:
-design, fabricate and test different versions of chip to give the optimum tissue structure and function that most closely
resembles the lung tissue.
-develop the supporting hardware and software to control fluid flow, sample collection and measure the barrier.
-develop simplified methods to make lung cells from adult human stem cells.
-use the Smart Biochip to test drugs provided by pharmaceutical collaborators.
This new technology has the potential to more accurately predict responses of lung tissue to drug therapies, shorten the
length of time of drug development from drug discovery to trials in humans and identify new drug targets. This system will
enable new experiments which will lead to an improved understanding of diseases of the airways. The platform will also
provide a simple, fast way to perform toxicology and pharmacology screens of new and existing drugs and compounds
such as aerosols that we inhale or exposed to in our daily life.

According to the recent European Respiratory Society White Book (European Lung White Book, 2013), respiratory
diseases especially asthma and chronic obstructive lung disease (COPD) have continued to be globally important causes
of death and disability during the past two decades. There is an urgent unmet need to reverse these trends and to provide
better medicines for patients. By optimising the research tools in the area of respiratory diseases the proposed project will
add a significant value to pharma-related research in this area, as evidenced by involvement of our pharma partner GSK.
The biochip platform offers potential for target identification and preclinical drug testing by pharma, as well as toxicology
studies. The impact of these innovations should be evident through uptake of the models by pharma within the next 5 years
leading to improvements in the T1 translational gap and enhancements in the pharma pipeline within 10 years. In the
longer term, through use of iPSCs, there is also potential for generation of patient-derived iPSCs allowing a personalised
approach that evaluates optimal drug combinations and highlight specific treatments for individual patients or groups of
patients with similar endotypes of disease.
Through linking with SAL Scientific, the project will also benefit this UK SME by generating patentable systems and
appropriate end-user feedback with investment potential for product development and commercialisation within 5 years. In
the broader context, the same technology is applicable to understanding and treating other respiratory diseases for
example cystic fibrosis, primary ciliary dyskinesis and chronic rhinosinusitis where patient derived iPSCs may be used to
develop disease-specific models. Furthermore, the technology platform will also benefit studies of epithelial barriers in other
tissues such as skin (cosmetic, topical treatments), GI tract (drug absorption), kidney and urogenital tract (drug excretion).
With appropriate commitment, these models could be implemented within 5 years.