Moving on from slight design modifications of testing chamber lid sealing that were made last week, we the team continued our discussion with Young Guang (client Graduate student) and Nick Thompson at 3D-printing center on medical campus, to actualize the product chamber for rst time (Detailed changes can be observed in the attached images. Circular pegs have replaced the “n” interface between the main body of the chamber and the lid for better leakage prevention.) On this Monday, the rst prototype of the drug-testing chamber was 3D printed. The actual product is presented in images attached, with keys for size comparison. The injection port was eventually not integrated into lid by printing, as our team still needs to assess the practicality of the dimensions of the main chamber. The purpose of this print will be to assess “workability” of the chamber, namely, if the design will be conducive to human manipulation, channel implementation, and gel loading. Our group still plans on exploring carbohydrate glass and are in the process of designing a mold for the sacrificial channel. Due to the fact that our scheduled meeting this week with our client Young Guang (client Graduate student) shall occur on Friday afternoon, this report contains information known and discussed within design team until Thursday. The meeting shall be dedicated to rst experiment design for qualitative testing for the 3D printed chamber prototype—corresponding results of the experimentation will be included in next weekly report.
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Most of the progress this week has been focused on chamber design. As such, most of this report will focus on proposed revisions to the preliminary design. These changes can be observed in the attached images.
The “fin” interface between the main body of the chamber and the lid has been replaced by circular pegs. From tests conducted by Dr. Setton’s summer students, the “fin” interface was prone to leakage and warping after multiple uses. The injection port is still absent from the top, as our team still needs to assess the practicality of the dimensions of the main chamber. We are currently scheduling a printing session next week with Nick Thompson to print this design. The purpose of this print will be to assess “workability” of the chamber, i.e if the design will be conducive to human manipulation, channel implementation, and gel loading. Our group still plans on exploring carbohydrate glass and are in the process of designing a mold for the sacrificial channel. However, most of our energy now is dedicated to fleshing out the main chamber design. We have also invited Dr. Yin to our SciNote team (LiSunTao) and project (SettonDrugDeliveryWork). The majority of this week was spent internally processing a lot of the comments we have received from last week. Due to the demands of classes and a busy week schedule, we have not yet met as a group to discuss our future direction. We hope to meet either this weekend or at the beginning of the next week in order to discuss our thoughts and findings to determine directions we would like to explore. Each of us has taken this week to re-evaluate the project direction in order to provide meaningful comments for our next meeting that will determine what methods we try and how we want to proceed moving forward, whether that means revising our timeline or re-structuring how responsibilities are divided up thus far.
Many events have transpired in the past week that have been critical in determining the direction of the project.
Our group thought that the feedback from Dr. Yin was especially informative. His immediate feedback motivated us to re-examine our guiding design parameters and spend additional attention on alternative technologies. However, we felt that because we did not thoroughly explain how our design timeline is different from other groups, a portion of our intent was misunderstood. After the preliminary presentation, we immediately scheduled a time to meet with Ali to thoroughly discuss Dr. Yin’s feedback and clarify our intent. Our meeting with Ali on the 14th was clarifying and useful. We will properly motivate eliminating preliminary designs by thoroughly explaining our thought process in the progress report. Because our design timeline will be focused more on testing and refinement, we will clarify differences in the next presentation as well. In addition to meeting with Ali, we met with Young earlier that day. We updated him on how we were proceeding. We was able to answer some questions we had about what solutes should first be used to evaluate diffusion through the chamber. Out of the standard markers mentioned in the grant, we will plan to begin with urea (“small” marker), albumin (“large” marker), Rhodamine B, and 3kDa dextran and evaluate them with the appropriate ELISA kits. We met with Nic Thompson on the 18th at the 3D printing suite to discuss channel design. We discussed the limitations of the sacrificial carbohydrate lattice we were planning to move forward with, which included the difficulty of creating a plastic mold that can resolve that small of a channel, retrieving the solidified glass rod from the mold without shattering, and the rod being able to maintain the stress from loading the PEG gel without bowing or breaking. After discussing these limitations, we began discussing alternatives. Instead of creating a sacrificial rod, we talked about using a syringe or needle to place in the chamber while the gel is loaded. Once the gel is loaded, the syringe or needle would be removed to create an open channel in the gel. A concern arose with shearing the gel during the removal process, which we thought could be remedied by coating the needle with some sort of lubricant. We also talked briefly about adjusting the chamber design. We will schedule a followup meeting with Nic after adjusting our approach and more thoroughly discuss changes in the chamber design in the next weekly progress report. In addition, we also have created our website: http://esyn.weebly.com/. We spent the majority of this week’s time devoted to the presentation and trying to finalize the details of it. I had put the presentation together prior to going to BMES, but finalized much of the details with my group on Sunday 10/9. Significant amounts of time were spent on rehearsing it and going over details to make sure that the presentation was good and something we were all comfortable showing to the rest of the class.
After the presentation, we decided to push off a lot of the emails we were planning on sending, along with our plans to move forward with the design and creation of molds in order to address a lot of the concerns that had been brought up during our preliminary presentation by Dr. Yin. We wanted to ensure that we had good metrics and a concrete idea of what we wanted to address moving forward. Thus, there was no significant progress made this week in terms of moving forward with the project. Instead, most of the time spent this week was devoted to thinking of the project, possibly restructuring it, and arranging meetings with people in order to address these problems. Our group is meeting with Ali later this afternoon to better understand the timeline, what is expected from our product, and how we could best move forward with the project that we have. We understand that our project is also a bit more unique in that we will require more time to test our product than other groups will. Thus, the original timeline we had proposed required for the test chamber to be put together by the beginning of second semester in order to leave enough time for us to test it as well. We are also meeting with our client later in the afternoon after our meeting with Ali to go over more specific metrics as well as provide a progress report. Good communication from both ends will ensure that they have a good understanding of where we are. Information discussed in these two meetings will be included in the following week's preliminary report. After finalizing these details, we hope to contact one of our collaborators who is an expert in 3D printing. From there, we can begin to design our testing chamber and try out various molds for use with the perfusable vasculature. This week our team continued to study and attempt on four major subjects: 1. Carbohydrate-glass lattice material proposed by Jordan S. Miller paper that was discussed in previous week's report 2. The E-SYN drug testing chamber design 3. Mathematical modeling of diffusion phenomena of typical drug particles in current design of E-SYN testing chamber 4. Preliminary report and the presentation for project.
Specifically, during the week Arnold mainly focused on putting together the preliminary report and the presentation. Arnold also planned out a timeline with our client associated graduate student Young regarding when our team will be able to complete molds for our E-SYN drug testing chamber. Arnold is also in the process of reaching out to Nick Thompson at Washington University School ofMedicine to go over our needs and see if we can get a preliminary design mold to test in the Setton lab, which is scheduled sometime next week. In addition to collective discussion of the preliminary design of the device that will serve as the platform of our test, Richard has been working on 3D design of E-SYN drug testing chamber in Autodesk Inventor software and technical drawing for illustration of current design. The corresponding files of the 3D models and technical drawings are uploaded to SciNote. Moreover, a preliminary mathematical diffusion model for current rectangular 3D E-SYN drug testing chamber was also attempted by Richard in COMSOL software. Most of our team's time this week was spent on preliminary report and the presentation preparation. Next week is planned to be more experimental and lab-focused. Device design is proceeding well. Last Friday, Arnold spent some time in the lab assessing the viscosity of carbohydrate glass, composed of glucose, sucrose, and dextran, at high temperatures. We noted that the composite was viscous at 70C, the maximum printing temperature of the BioBots printer we were looking to use.
On Wednesday (9/28), Dr. Setton, Young, Arnold, and I met with Dominic Thompson, a staff scientist who manages the biomaterials/3D printing suite in the CSRB. We discussed different materials, including HIPS, PVA, and carbohydrate glass. He recommended that we create ABS molds for the carbohydrate glass channel instead of using the viscous carbohydrate composite as a printing material. Using reusable molds would allow us to construct the channel in-house (at the Setton Lab) rather than having to transport material back and forth between Danforth and CWE. In addition, we were informed that the resolution of the printer was suitable for our purposes (printing channels with diameters of 500 um to 1000 um, lower limit of 200 um). We will be following up with Mr. Thompson to schedule a design session to help us model the mold in CAD/Inventor. Overall chamber design is still in preliminary stages. Our first mockup will consist of a rudimentary rectangular design, similar to the old design but adapted to accommodate the new materials being used. A 3D printing file will be drafted by the next weekly report. From our meeting on last Friday with Young, a graduate student from our client Setton lab, we gained deeper and more significant insight of the project and where our design shall be positioned in the larger scheme of the entire grant funded project. It was very important for us to see the orientation and unique approach of the actual scientific research at the scope of administrator, which is indeed a very different perspective than what all of our team members have previously experienced as student research assistant.
Besides drawing and learning information from literature we were given by client as referred in our previous week’s report, we also continued to search for additional key techniques for the problem we are facing in the project. After relentless self-educating and discussion on specific aims of the design project, our team have completed the Scope of the project which has been submitted to Dr. Yin. The process though which we obtained most knowledge of the field of osteoarthritis (OA) and current drug delivery system was writing the Scope, trying to summarize significance of client’s need. In addition to collective discussion of the preliminary design of the device that will serve as the platform of our test, we have divided early stage work into three divisions for three team members—Arnold will primarily focus on the material fabrication process, David will concentrate his time on idea examination of novel designs of vessel device, and Richard shall spend time in charging of the dynamic diffusion modeling of the preliminary design in geometry and mathematics. This Friday afternoon at 1pm, we will meet with our client associate Young again for a tour in our client Setton Lab for familiarization of currently standing research facility and techniques. The update from the tour shall be included in next week’s weekly report due to deadline requirements. This week we were given reading to do in order to learn the necessary background knowledge for this project. This reading involved a grant submitted by the PI, Dr. Setton, a review article on Intra-articular drug delivery systems (Burt, 2009), a textbook chapter titled Synovial Fluid and Trans-synovial Flow in Stationary and Moving Normal Joints, and a Nature materials publication on the casting of vascular networks by Dr. Chris Chen's lab at Boston University. These papers were very interesting and provided a lot of insight into what made this drug delivery model so complicated. Further, the paper from Dr. Chen's lab provided a lot of ideas on how to better create the system we wanted to model.
After reading these papers, we met with Young, a graduate student in the Setton lab. Dr. Setton was out of town and thus, unavailable to meet this week although she will be there for future meetings. There, we discussed a lot of ideas for how we thought it best to tackle the problem. A few key points we all seemed to agree on was that the model should be a closed system with one part. Further, we decided to give Dr. Chen's method of creating a carbohydrate glass material a try in order to completely replace the gel and embed collection tubules directly into the model design. After drawing these conclusions, we established a timeline that works well for all team members. By the October deadline, we plan to have come up with a broad idea of how we want the model to look and what main features we want to include in it. We also established that within the next week we wanted to start looking into creating the carbohydrate glass material that will serve as part of our gel. We received a contact, Dominic Thompson) at the WashU medical school, who had helped Dr. Setton previously with 3D printing. We plan to reach out to him next week in order to discuss our plans further and see what capabilities his facilities can offer us. Richard, David, and I have also decided to meet this weekend in order to further discuss the project. We will also be meeting again with our cient next Friday to tour the lab space and discuss more experimental details. Our group met with Dr. Lori Setton and PhD candidate Young Guang last Thursday morning (9/8) to discuss “E-SYN”, a model bioengineered synovium. Prototypes were developed by undergraduate researchers over the summer. The design team would be involved in redesigning a test chamber to evaluate drug transport and bioactivity in cell-laden hydrogels. A major goal of the project would be improving compatibility between the test chamber and the hydrogel. This involves downsizing the current design and selecting appropriate materials to assure optimal fluidics, biocompatibility for drug clearance, and overall biomimicry.
We followed up with Dr. Setton and Young later that day, expressing our interest in the Setton Lab and E-SYN. We will be meeting with Young on 9/16 to clarify project goals. |
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April 2017
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