Cancer is the second leading killer of Americans, claiming over half a million lives annually. The most powerful predictor of cancer mortality is its ability to metastasize to distant sites in the body. Much of this spread occurs in blood and lymphatic vessels yet effective methods for studying cells in these environments remain undeveloped. We have designed and fabricated a system capable of growing human cancer cells in a controlled environment similar to that of the human body. Such a system serves as an effective model for cancer metastasis and will allow researchers more experimental control than existing cell culture techniques.
Our device seamlessly integrates with existing cell culture technology. It consists of 96 precision-machined cone tipped rods that fit precisely into each well of a standard 96 well cell culture plate. The rods are connected via a custom gearbox to a commercially available motor capable of spinning at speeds in excess of 3,000 rpm. Our device is essentially a high throughput cone and plate viscometer capable of generating physiological shear stress to cells in-vitro. The motor can be programmed using any laptop computer. Such programs allow the user to precisely control flow velocity, shear stress and other variables in a time dependent manner. Commercially available membranes may be easily added to this system between the rods and the cell culture plates to model the phenomenon of metastasis. Testing indicates that near constant shear stress can be generated across all of the cells in the well with minimal cell loss.
The typical workflow of our device consists of the user first placing cells and growth media in a standard 96 well plate with added membrane. The user then places the plate into our device using a precision controlled optics stage. The device is then programmed using an easy to use graphical interface. An example program may be running the machine at 3 Pascals pulsing at 60 beats per minute to model the human cardiovascular system. The experiment is then run for the allotted time and cells passing though the membrane can be analyzed to determine the degree of metastasis.
We have modeled, fabricated and tested a working prototype of our design. Such a design can be easily scaled into mass production, as a majority of parts are commercially available. All other parts were machined using inexpensive corrosion resistant aluminum. This design has numerous applications in any biomedical research facility including both private pharmaceutical companies and public research universities. It will allow researchers to model complex phenomena such as cancer metastasis in a high throughput fashion, saving both time and money. It will not only increase our understanding of such phenomena but will also provide for the development of life saving therapeutics.