System Level Design

Team Vision for System-Level Design Phase

Summarize:

• In the System Level Design phase, we planned to work on breaking down components of the printer that we hope to design and/or improve, and will brainstorm creative, reasonable, and testable designs. Specific aspects that we hope to focus on include print head mounting, printing nozzle design, printing parameter control, syringe pump automation, biomaterial selection, and the introduction of cells into the system.
• During this phase, we created a list of functions and subfunctions of the bioprinter that we hope develop and optimize, and determined how various inputs such as biomaterials, print settings, and energy will flow through the device to produce a successful print. We conducted benchmarking research on current bioprinters on the market, hydrogels, cells, pressure systems, extrusion methods, and crosslinking techniques, which led to the development of a variety of concepts that could perform our specified functions. These concepts were refined in a morphological chart and combined to generate systems-level concepts. Each systems-level concept was evaluated in iterative Pugh matrices based on criteria that we deemed important for a functional bioprinter. Once the optimal design was selected, we brainstormed benchmarking, analysis, and prototyping based feasibility studies to perform that will ensure our design is reasonable and finalize undetermined aspects of our design. A high level view of our design was developed to help us start thinking about how to build the bioprinter. Lastly, we reassessed the risks specific to our selected design. Apart from the assigned work, a few of us were able to go into the lab to play around with the current prototype with guidance from Nick Lee, who worked on this MSD project last year. We also met with Dr. Dan Reynolds, an engineer at Harvard who works with 3D bioprinters to learn more about how they are used in research. Finally, we met with Dr. Iris Rivero, a professor at RIT who also conducts research using 3D bioprinters, and gained some useful insight on what designs might work well for our project and application.

Functional Decomposition

Purpose

Define the total list of functions and sub-functions, based on the Customer and Engineering Requirements, that must be delivered by the final design. This will establish the need for specific concepts necessary to deliver the overall objectives of the project

Link to live document: https://drive.google.com/file/d/1lbt_kAx-mnheHmDaob9_RI4Q8a1_usYW/view?usp=sharing

Benchmarking

Purpose

Avoid redundant work by identifying already available solutions and concept options

Problem Statement:

• Current State

• Industry - able to print hydrogels and live cells for tissue engineering applications

• MSD - 3rd generation project

• Desired State

• A fully automated demonstrational device capable of printing hydrogels and cells as a solid matrix

• Key Goals and Deliverables

• Selecting biomaterials and printing parameters that support cell growth and retain desired print shape

• Incorporation of multiple materials 

• Automating syringe pump control

• Mounting of the print head

• Key Constraints

• Utilizing the previous prototype

• Maintaining cell viability

• Creating a printer that can be easily transported

Commercially Available Printers:

• Biopixlar 3D Single-Cell Bioprinter
• Allevi 1*
• Cellink Inkredible*
• Cellink Bio X
• Ourbotics Revolution
• Poietis NGB-R
• Advanced Solutions BioAssembly Bot
• EnvisionTEC 3D-Bioplotter Developer Series
• Alpha Series 3Dynamic Systems
• Rokit Invivo
• RegenHY 3DDiscovery Evolution
• SunP Biotech Biomaker*
• AGS1000 Gantry System
• Existing Prototype (P20677)**

Criteria Examined (desired criteria below):

Concept Generation

The integral functions/components of the 3D bioprinter were identified. For each function or component, possible concepts were brainstormed and compiled. These concepts were narrowed down into a final list (below), to be used in the creation of the morphological chart. Items with an asterisk (*) were not elaborated on, as they have already been addressed and were deemed acceptable in the pre-existing prototype.

Key functions:

• combine cells and material
• store and push/force material
• extrude material
• crosslink material
• control extrusion pressure
• move nozzle *
• receive print *

Key components:

• material type
• cell type
• casing/structure

Final concepts for each function/component:

1. Combine cells and material
   1. mix uncrosslinked biomaterials and suspended cells manually
   2. have a separate printhead to flush each layer of hydrogel with cells
   3. two printheads simultaneously printing cells and hydrogel
   4. manually embed cells
   5. mix through two separate channels before print head
   6. mix with microfluidic system in print head
2. Store and push material
   1. high capacity syringe with fixture to attach to gantry system
   2. side-mounted reservoir on printer with metal fixture for nozzle
   3. hypodermic needle and slotted laser cut acrylic
   4. external reservoir and hypodermic needle fixture
3. Extrude material
   1. release at a rate in the laminar flow region (constant flow)
   2. drip/shoot out tiny blobs of bioink
4. Crosslink material
   1. UV source on exterior, outside of and attached to the nozzle
   2. UV source on exterior, complete separate source
   3. UV source on interior of nozzle
   4. UV source that passes after each layer
   5. Ionic crosslinking within the nozzle
   6. Ionic crosslinking using separate nozzles
   7. Ionic crosslinking, printing into a bath of crosslinker
   8. Ionic crosslinking, manually add after entire print
5. Control extrusion pressure
   1. syringe pump
   2. pressure box attached to external reservoir and tubing
   3. peristaltic pump
   4. screw that pushes material down
   5. piezoelectric print nozzle
6. Material type
   1. sodium alginate
   2. gelatin
   3. alginate and gelatin mixture
   4. methacrylated gelatin
7. Cell type
   1. 3T3 fibroblasts
   2. Osteocytes
8. Casing/structure
   
   1. closed printing environment
   2. open printing environment

link to the live document with all iterations of the process: https://docs.google.com/spreadsheets/d/1nPsAHjBqwzWndaK6HoQEWHDY8r6qu4ItMcbopka6OwA/edit#gid=1659385401

Feasibility: Prototyping, Analysis, Simulation

Bioprinting

• What extrusion speed of the bioink is compatible with maintenance of 50% cell viability when printing continuous gel strands?
  • Analysis – test different extrusion speeds and measure cell viability post-print
• Can the selected cells and materials be combined in a homogeneous mixture?
  • Benchmarking – research cell and materials to see if they can be combined in a homogeneous mixture
  • Prototyping – try out various combinations of cells and materials to see how well they combine
• Can cell and material concentrations be adjusted such that a final material with appropriate mechanical properties is produced?
  • Benchmarking – determine mechanical properties of material and cell combinations
  • Prototyping – try printing bioinks of varying concentrations of biomaterials and cells to see how they print
  • Analysis – test mechanical properties and print dimensions
• How will we implement UV crosslinking?
  • Benchmarking – look up how UV crosslinking is done in current bioprinters
  • Prototyping – try out different placement and timing of UV exposure (continuous in nozzle, continuous outside nozzle, after each layer outside nozzle)
  • Analysis – determine mechanical properties and cell viability post crosslinking
• Are the selected cells (3T3 Fibroblasts) appropriate for this application?
  • Benchmarking – see if these cells are used for 3D bioprinting
  • Analysis – test out how well the cells print (integration with biomaterials pre and post print, survival during printing process, attachment and proliferation after printing)
    
    

Mechanical, electrical, software

• Is the current electrical control sufficient for our concept needs?
  • Analysis – perform several test runs and try to implement conceptual elements as close to the true concept as possible, evaluate electrical performance during test runs
• What printer head nozzle type/design is best suited for the intended goal?
  • Benchmarking – explore the literature of 3D bioprinting and see what well-funded, established entities are using for their printer head nozzles and types
  • Prototyping – we have identified a promising solution that is publicly available to use - we are hoping to test this solution out against other potential prototypes that team members may be able to identify or that previous project members have attempted to implement
• How heavy can we have the print head?
  
  • Prototyping – design several print heads of varying weight and test their functionality (or lack thereof) during a test print
• What is the minimum pressure the pump needs to produce for extrusion?
  • Benchmarking – use the available literature to see what other groups have used for pressure of printer pump to properly extrude
  • Analysis – perform several test runs of print with varying extrusion pressures and compare results of print jobs or material extrusion quality
• What is the best practice to limit bubbles in the reservoir?
  • Benchmarking – use the available literature to compile a list of methods that entities have used to limit bubbles
  • Prototyping - design and implement several potential methods to test

Morphological Chart and Concept Development

The key functions and components from the concept development phase were split into two categories: bioprinting and electrical/mechanical. A morphological chart was created for each category. Using these morph charts, different system level concepts were created. Electrical/mechanical concepts were chosen assuming standard electronics/motors and print bed heating, as set by the pre-existing prototype.

The bioprinting morphological chart.

Concepts associated with the bioprinting morphological chart.

Electrical/mechanical morphological chart.

Concepts associated with the electrical/mechanical morphological chart.

link to the morphological charts: https://docs.google.com/presentation/d/1T3tHGXhYWpnVKD-Q1AracsQLCnmqAOl-E6wzxZzDMcM/edit#slide=id.p4

compiled list of links for the images used in the morphological charts: https://docs.google.com/document/d/19Ww0uoKWpIvSux6cb5mh-q4Z83Gedad4YIOh_EM_CtY/edit

Evaluation Criteria

The following criteria was used to compare the merits of complete system design concepts in the form of a Pugh Matrix evaluation:

• Biocompatibility

• Transportability

• Automation / Lack of User Intervention

• Clean Extrusion / Lack of Clogging

• Compatibility with Existing Model

• Compatibility with Existing Software and Electrical Methods

• Short Print Time

• Print Robustness - Accuracy

• Print Robustness - Resolution

• Print Robustness - Structure

Designs that performed well in the Pugh Matrix evaluation were also considered in regards to the following criteria for feasibility within the course constraints of MSD:

• MSD Budget Restriction

• MSD Time Restriction (2 semesters)

Pugh Matrix and Concept Selection

Concept selection using a Pugh Matrix was divided into two evaluations: bio-ink aspects and mechanical printer aspects. All screening was done by objectively evaluating each system design against the previously determined criteria. Each iteration, the concepts were compared to a datum concept. The datum concept changed with each iteration in order to gather more information through multiple comparisons. Two iterations were performed for both concept types.

Bio-ink Pugh Evaluation: Iteration 2

Mechanical Printer Pugh Evaluation: Iteration 1

Link to live document: https://docs.google.com/spreadsheets/d/1uOwJrFNzjey4eBYSlr1h5vnA6o4oGAkmV7lYnm7qcnk/edit?usp=sharing

Final Concept Selection

After performing Pugh Matrix evaluation, the resulting concepts were evaluated against the MSD course constraints of time and budget. The resulting final concept selected is shown below:

Systems Architecture, Designs, and Flowcharts

Purpose

1. Ensure flow of energy, info, material and structural forces as intended.
2. Define subsystem functions, envelopes and interfaces.
3. Define a high-level view of the elements required to build and operate the entire system

Risk Assessment

NOTE: The above risk assessment chart only lists the added risks from this phase that were identified based on the selected system-level concepts. For risk items 1-24, please refer to the links below.

While no risk items were directly resolved or mitigated as a result of the work done during this phase, risk items 1 (print head clogging), 2 (extrusion shear being too high), 3 (hydrogel not conducive to cell viability), and 10 (cell to matrix interaction) were considered in the process of finalizing the team's preliminary selection of a concept design for both the bio-ink and printer mechanics aspects. The selected concept design will ideally be geared towards preventing these risks from appearing during operation of the printer.

The intention is to experimentally address other risk items through the methodologies outlined in the team's work for feasibility of concept elements. By using literature, iterative work, and experimental techniques/devices, the goal is to minimize the potential occurrence of as many risks as possible.

To review additional details of the previously mentioned risk items, please refer to the links below to redirect to the appropriate source(s). 

Full Risk Assessment table for System-Level Design Phase: https://docs.google.com/spreadsheets/d/1x-HgpAEgWg664OcvOgKyGW2yofhxgaWGK2TQCsr1yPc/edit?usp=sharing

Cumulative Risk Assessment table folder: https://drive.google.com/drive/u/1/folders/13s4b1JUzFEB5C3w8IigbIvXkpZtdMSWQ

Design Review Materials

Include links to:

• Pre-read: https://docs.google.com/document/d/1CAmbPufFyHwXrWP1PWlSbfv2CeRNL_J4MXE7wpN5FM8/edit?usp=sharing
• Presentation slide deck: https://docs.google.com/presentation/d/1aTKv8inabgwVkVmT7U7q_vtVDJFKy4fkxnFX53PzwXw/edit?usp=sharing
• Notes from review: https://docs.google.com/document/d/165soYJ81FoGY3zJhmd381fyNdM6HJEOQ6b9Rlz03lBw/edit?usp=sharing

Plans for next phase

In the Preliminary Detailed Design phase, we will divide work and develop specific schedules for the bioprinting and mechanical/electrical/software teams. Each team will work on design and conduct feasibility tests for their appropriate subsystems in order to determine viability of the selected concept and discover necessary adjustments to the system. Specifically, some feasibility tests that will be conducted include cell and material combination, crosslinking implementation, compatibility of existing electrical equipment, print head design details, and extrusion pressure limits.