Design Spotlight - Agile Prototyping
My Philosophy
The road to progress is paved with extensive trial and error. No project is ever perfect on the first attempt and I strongly believe that the key to the development of a project is agile prototyping. By utilizing strong prototyping skills and a flexible mindset, I have always allowed my teams to move rapidly and make progress that would be otherwise impossible.
-Adam Savage, Mythbusters
Cell Extraction Solution
Obstacle
A 2mL thawed cryo-vial of cell solution is welded into an existing tubing set. All of the cell solution must be extracted without lysing (damaging) the cells and the vial must be thoroughly rinsed with growth media. Additionally, the vial may begin frozen meaning any modifications to the vial cap may not extend beyond half of the height of the vial.
Prototyping Process
Existing Solution: The vial cap has a vent and a dip tube. The vial is repeatedly drained of cell solution and rinsed with growth media. This takes 10 cycles to achieve the desired fluid rinse.
Areas of improvement: The rigid dip tube would not fit into a vial with frozen contents and the process time is lengthy and requires many distinct fluid transfers which cause damage to the cells. Additionally, the many distinct transfers can cause foaming of the growth media.
Inspiration: I recalled a clever method of fluid transfer called the “Mariotte Bottle” which creates constant flow from a vessel with a dynamic head height. Although the Mariotte bottle solves a different problem, the simple and clever design lead to unconventional ideas that eventually evolved into the ultimate solution.
Design Solution
The final design is a non-vented vial cap with two separate dip tubes. The input is the high dip tube and the output is the low dip tube. The non-vented cap creates a face seal around the lip of the vial and pumping into the high pickup pushes a slug of air into the vial first. This pressurizes the vessel and pushes the fluid down and out of the low pickup. Once the growth media reaches the vial it is dripped in through the high pickup and mixes with remaining cell solution before being pushed out of the low pickup. As demonstrated below, it only takes ~5mL to dilute the original cell solution to negligible levels.
This design has many advantages over the existing solution. The cell extraction and media rinse are performed in one continuous delivery and extracted cells do not need to run through any pumps to reach the destination. Additionally, fluid is always delivered above the fluid level, minimizing media foaming. Finally, the simplicity of the design requires no complicated hardware or software efforts. Currently this design is still in development, and initial testing have yielded excellent results in both cell recovery percentage, cell viability and decrease in process time.
Diagram of prototype cell extraction vial
Preliminary P&ID Layout
Obstacle
At the onset of a cell culturing project, the initial feasibility testing was drawing to a close and the next phase of development was set to begin. The old feasibility system needed to be dismantled and replaced with a new concept level system.
Prototyping Process
Time frame: the layout needs to be completed in a two week time frame and would not have access to machined components.
Independent Investigation: the entire process needed to be primarily independent.
Areas of improvement: In addition to added functionality, the system required a major overhaul to increase usability, strengthen the rigidity of the structure and improve tidiness/cable management
Design phases:
Determine P&ID layout given system requirements
Perform a rough CAD mockup to lay out components in space
Source and order required components
Assemble system and corresponding tubing set
Design Solution
The final system layout is shown to the right. The front facade is 1/8” white acrylic with hand drilled holes for pneumatic fittings. The tubing set was arranged in configuration to reduce residual fluid, trap air in designated areas and interface specifically with the bioreactor. The valves and pumps were retained by 3D printed clips that can be easily and quickly inserted allowing convenient installation of the tubing set.
Concept 0.0 system layout
Custom Fitting Development
Obstacle
While developing the process for an automated cell culturing system, multiple diaphragm pumps were tested at multiple orientations. This required the connection a tangential flow filter (TFF) and a custom made pump in multiple configurations. Unfortunately, the fluid connection on the diaphragm pump was entirely custom and the connection on the TFF (3/4” tri-clamp) was obscure and incompatible with existing supplies. A custom fitting was required to connect these two drastically different components.
Prototyping Process
Agile development: Due to the rapidly evolving nature of the project phase, the part needed to be 3D printed so that different configurations could be tested and variations could be implemented on a short time frame.
Usability: the fitting must be able to be installed and uninstalled easily from both component
Fluid seal: the fitting must create a reliable water tight seal around both components.
Material Consideration: The fitting must be able to be used in sterile cell processes, meaning the material must be sterilization compatible and biocompatible.
Design Solution
Shown to the right are three different configurations of the custom fitting and a cross sectional view of the fit with the diaphragm pump. The top of the fitting interfaces with the TFF by fitting in a standard gasket and clamping to a corresponding side of a TFF. The flexible clip side of the fitting interfaces with the diaphragm pump by inserting the O-ring into a tapered opening and the snap-hook latches onto the back of the pumps housing. The length of the snap-hook was calculated to specifically maintain the desired compression of the O-ring.
All fittings maintain a reliable fluid seal and the material is biocompatible as well as compatible with the labs autoclave. Additionally, design steps were taken to make the designs injection molding compatible for future developments.
