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Cell Recovery System for a Cell Therapy Medical Device

TEAM 16 MAE156B WINTER 2012

SPONSORED BY

WHO IS VIACYTE?

ViaCyte, Inc. is a biotech company conducting research in stem cell engineering to create cell therapies for diabetes. The company is currently working on a stem cell implanting method to create insulin independence without immunosuppression, hypoglycemia, or other diabetes-related complications in patients.

BACKGROUND

-The Current Cell Recovery Process-

ViaCyte is developing an implantable cell therapy product that is retrievable, non-biodegradable, vascularizing, and allows nutrients necessary for survival and function of producing cells. To deliver cells to the device component the cells are thawed, monitored, maintained and loaded into cell chambers manually by a skilled operator. This cell recovery and loading process places stringent requirements on the operator to ensure the safety, viability and sterility of the cells. In addition, the cell chambers used are small and non-scalable, which leads to excessive handling and risk of potential contamination of the system to meet demands for clinical manufacturing.

Our team was given the task of reducing these concerns by automating the cell recovery process that will provide a closed, scalable system for clinical applications.

***For an abstract summary of our project please refer to the Executive Summary***

OBJECTIVE

-Automating the Cell Recovery Process-

FINAL DESIGN

The automated cell recovery process is illustrated on the diagram as shown (left). In this cell recovery system, frozen stem cells must be thawed in an incubator within a bioreactor containing ports for: fluid addition, dead cell removal and live cell extraction. To prevent cell adhesion, a stirring base induces shear into the fluid and separates the live cells from the dead. When the cells are thawed and ready the bioreactor must be tilted to allow for collection of all live cells. With this information in mind the project was divided into four components with the following requirements:

Bioreactor
- Must be sterile, aseptic, and disposable
- Meets Class VI or ISO 10933 regulations
Stirring Stage
- Provides variable speeds (10-80 rpm) and variable radii of rotation
- Supports maximum of 9.0718 kg (20 lb)
- Able to function within a 46.26 x 46.26 x 46.26 cm (19 x 19 x 19 in) incubator
Tilting Stage
- Provides variable set angles for live cell collection
Control System
- User-friendly interface
- Control length of time for stirring - 24hr
- Control RPM of stirring - 10 to 80
- Control length of time for settling - 6 min
- Control volume of fluid pumped in and out of Bioreactor

- Bioreactor -

Houses the cells throughout the thawing phase.

- Vessel is of a modified 500 mL Nalgene container
- 4 ports each for a specific duty:
  - Dead cell extraction
  - Live cell extraction
  - Insertion of fresh media
  - Ventilation
- Peristaltic pumps control fluid movements

- Stirring Stage -

Designed to provide a smooth and stable rotation with an adjustable radius of rotation within incubator.

- 3 levels of aluminum plates, stainless steel guide rails, and ball bearing carriages
- Supports weight of 9.0718 kg (20 lb)
- Crank slots offer radii of 1.27 cm (0.5 in) to 8.255 cm (3.25 in)
- Crank slide component secures top plate (transparent) onto slots of crank
- Driven by a high torque stepper motor

- Tilting Stage -

Allows for variability in set angle to guarantee removal of living cells.

- Built of steel to provide easy maintenance

9 different angles (~10 degrees apart)

- Control System -

Controls pumps for extraction/insertion of media and stirring stage during the cell recovery process.

- Programmable elapsed time clock
- Stepper motor controller for stirring stage
- Two servo driven peristaltic pumps
- Ability to operate as standalone system
- USB enabled Windows application allows user to edit variables.

PERFORMANCE

The system prototype was tested for a duration of 24 hours, where the following operation process was conducted to simulate cell recovery.

- Bioreactor -

Using magnetic beads to simulate the thawing of stem cells inside the bioreactor the goal of no cell adhesion was obtained. The stirring stage induced enough shear into the container to prevent settling. It was discovered that cells would clump around the feeding/extracting hoses, however this did not affect any process of the system.

- Stirring Stage -

The stirring stage was able to rotate at various speeds and radii of rotation. At the maximum radius of rotation, 8.255 cm (3.25 in), the stirring stage remained within the incubator base dimensions of 46.26 x 46.26 cm (19 x 19 in). The table was able to support a 9.0718 kg (20 lb) weight and rotate smoothly with no noticeable difficulties.

- Tilting Stage -

When it was time to extract the cells the optimum angle was found to be ~30 degrees.

- Control System -

The controls were able to accurately remove the top layer of bioreactor fluid, refill the bioreactor with new fluid and power the stirring stage at variable speeds. The sensitivity of the control parameters was tested and adjusted to provide the highest level of accuracy.

ViaCyte’s research on stem cell therapy will have an enormous impact on society once it is perfected. Diabetes affects around 285 million people around the world. Providing an effective therapy for diabetic patients will help millions of people who struggle with their insulin deficiencies. Once this therapy can be perfected and produced at a reasonable cost, significant progress can be made towards controlling diabetes. The system designed will reduce the amount of manual labor required and error involved in thawing frozen stem cells. Speeding up the process for thawing the stem cells will reduce the cost of producing the final product.

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