Organ/Tissue-on-Chip

Organ-on-a-Chip platforms can mimic the functions of individual organoids or entire organ systems. This is done by placing and maintaining tissue biopsies or cells within a microfluidic flow cell. Media can be pumped as desired and allowed to perfuse the cells with nutrients and oxygen, and then exit the system, removing waste products.

Organ-on-a-Chip technology has the potential to transform drug development. It constitutes an alternative to often unreliable animal models. A patient’s own tissue and cells can even be used in an Organ-on-a-Chip system, enabling personalised drug development.

Researchers at the University of Hull have pioneered maintenance of tissue biopsies on chip. We have developed a range of devices for maintenance of tissue biopsies from brain, liver, gut and skin as well as cancer tissue. Furthermore, we have developed a range of devices for spheroids and devices enabling the study of cell barriers.

Tissue Biopsy Devices

We have designed a range of flow through devices that can house and maintain tissue biopsies for perfusion. These devices are usually milled from polymer and interconnect to tubing through standard thread or push fittings.


Our first flow cell for tissue maintenance was fabricated from glass, featuring a tissue holding chamber with an inlet and outlet. The tissue was loaded though a PEEK microport. This type of device has been used for the study of liver tissue, glioblastoma and head & neck cancer tissue.

Publications: [1] Hattersley, Dyer, Greenman, Haswell, Development of a microfluidic device for the maintenance and interrogation of viable tissue biopsies, Lab Chip, 2008, 8, 1842. [2] Hattersley, Greenman, Haswell, Study of ethanol induced toxicity in liver explants using microfluidic devices. Biomed. Microdev., 2011, 13, 1005. [3] Bower, Green, Kuvshinova, Kuvshinov, Karsai, Crank, Stafford, Greenman, Maintenance of head and neck tumor on- chip: gateway to personalized treatment? Future Sci. OA, 2017, 3, FSO174. [4] Olubajo, Achawal, Greenman, Development of a Microfluidic Culture Paradigm for Ex Vivo Maintenance of Human Glioblastoma Tissue: A New Glioblastoma Model? Translational Oncology, 2020, 13, 1–10.

Our skin-on-chip device is designed to model human skin biology and wound healing. The chip takes full thickness human skin biopsies, that are perfused with media at the bottom and have air/gas access at the top. As part of on ongoing project, the device has allowed full closure of partial thickness wounds within 7 days. The chips are reusable and can be cleaned and autoclaved.

Device for Mimicking Barriers

Gut chip and blood brain barrier chip connected together

We have developed a range of dual flow devices, with independent flow above and below a permeable membrane or tissue biopsy carrier. This multi-purpose device design is suitable for biopsies, tissue slices and cell cultures, by the use of interchangeable disposable carriers. Such devices allow mimicking of bariers, for example as gut-on-a-chip models or blood-brain-barrier models. The devices can also be daisy-chained for more complex multi-organ models.

Publication: Dawson, Dyer, Macfie, Davies, Karsai, Greenman, Jacobsen, A microfluidic chip based model for the study of full thickness human intestinal tissue using dual flow, Biomicrofluidics, 2016, 10, 064101.

Devices for Tissue Slices

We have designed a range of devices to house precision cut tissue slices. The perfusion device shown here features sintered pyrex disks to retain the biopsy in the device and permit perfusion with medium. The device consists of two milled PEEK plates with drilled recesses to house the sintered disks and biopsy sample. PEEK is used for its biocompatibility and good mechanical strength and chemical stability. The device is bolted together. Tissues were found to remain viable for at least 68 h. This chip was designed to study effects of radiotherapy on tumour biopsies.

Publications: [1] Kennedy, Kuvshinov, Sdrolia, Kuvshinov, Hilton, Crank, Beavis, Green, Greenman. A patient tumour-on-a-chip system for personalised investigation of radiotherapy based treatment regimens. Sci Rep, 2019, 9, 6327. [2] Riley, Green, Cheah, McKenzie, Karsai, England, Greenman. A novel microfluidic device capable of maintaining functional thyroid carcinoma specimens ex vivo provides a new drug screening platform. BMC Cancer, 2019, 19259.

 

  

Our Liver-on-a-Chip device architecture was optimised using COMSOL simulations to enable the best possible mass transport of oxygen to the tissue and thus better simulate in-vivo oxygenation conditions. Two PDMS gas exchange membranes house the precision cut liver slice within a nylon mesh carrier. The chip provides fluidic control and continuous supply and removal of media, permitting effluent analysis.

Publication: Christensen, under review

Spheroid Maintenance Devices

Spheroid are three-dimensional bundles of cells that simulate organ tissue more realistically than a two-dimensional layer of cells. Spheroids-on-chip can be used, e.g. to investigate cancer metastasis.

Our flow-through spheroid device is fabricated from polymer and features push connectors. Fabrication cost is low such that we are employing this as a ‘single-use’ system.

We have also developed glass microfluidic flow cells with chambers that allow placement, study and microscopic observation of spheroids. These are currently applied to investigate the effects of hypoxia on cancer cells.