Cell Fluidics Engineering
From February 2023 to the present I worked as a mechatronics/biomedical engineer at CellFE.
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CellFE has developed a scalable, high throughput microfluidic technology for the efficient delivery of gene-editing molecules into cells. CellFE’s technology uses rapid cell compressions to induce a unique behavior causing cells to exchange fluid with the environment and uptake large molecules. The technology has demonstrated the delivery of mRNA, CRISPR Cas9 protein, and plasmid DNA without a negative impact on proliferation, immunophenotype, and exhaustion of the transfected cells.
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CellFE’s device induces rapid compressions on cells, causing temporal loss of intracellular fluid and cell volume decrease. Following the compression, cells recover volume and actively uptake fluid and materials from their surroundings. This convective transport mechanism is extremely effective in carrying target material into the cell ‘s interior, with a low impact on viability. This process occurs in milliseconds as opposed to seconds for other technologies and does not require an incubation period.
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High Throughput Novel Mechanoporation Device
I designed a novel mechanical device at my current company (CellFE) that compresses high volumes of biological cells and affects them with a payload to change their genetic structure.
This device involves a pressurized inlet reservoir that pushes volumes of cells through a series of microfluidic chips that compresses the cells. The microfluidic chips are interconnected with complex 3D gaskets with ridges that provide a tight and consistent seal between chips without mechanical failure. These gaskets were designed iteratively inhouse through in house 3DP molding with silicone rubber injections.
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I designed a test fixture to evaluate various gasket designs and iterated upon failures such as chips cracking and gasket blowout. This device was run with biological cells, which proved parity with our companies current transfection rate enabling much higher volume throughputs.
Tests were also run on the device to ensure that pressure drops did not occur, volume recovery was reasonable and pressure rise time was acceptable.
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Several sensor ports were incorporated into the consumable for feedback and evaluation. Such as a pressure sensor port and a flow sensor port.
This was the first project I really got to lead as a full time engineer and I learned a ton from it. Would love to discuss it more in person!
Mechanoporation Instrument
I assisted in the R&D development of CellFE's low throughput instrument. This instrument essentially delivered pressurized air to process a cell payload through a polycarbonate consumable into a microfluidic chip to begin the process of transfection.
Alot of the initial design work was contracted out to an engineering firm. I played a large roll in discovering critical use problems and resolving them. One example of this was discovering that the burkert valves we were using were leaking when in a closed state. This would register a small amount of airflow on the sensor end and prevented the instrument from starting a workflow. This was a difficult issue to diagnose to begin with since there wasn’t too much instrument feedback on why the workflow was not starting. I had to look at individual pieces of the instrument and perform tests to discover the root cause. Ultimately this theory was confirmed by doing a laminated tape test on the burkert valves.
To mitigate this issue I opened up the valve under a microscope and discovered small metal shavings on the inside that were obstructing the pathway. I flushed the valves with isopropyl alcohol and verified that the cleaning solution worked. I then instructed our contract manufacturers to implement a deep cleaning procedure before assembling the instrument and to put filters upstream of the burkert valves. I verified that this solution mitigated this problem by writing cycle test cases in python to validate the functionality of the instrument.
Mechanoporation Chip
I spearheaded the development of a specialized leak test fixture designed to categorize consumables based on internal microfluidic chip characteristics during a flow rate test. This involved a multifaceted approach, including the identification of key factors contributing to inconsistent flow rates, and the design of new chips to isolate these characteristics.
Identification of Inconsistent Flow Rate Factors:
I conducted an in-depth analysis to identify the key factors contributing to inconsistent flow rates within the microfluidic consumables. This involved a examination of internal chip characteristics and their impact on flow dynamics.
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Design of New Chips and Dataset Generation:
To address the identified issues, I led the design and development of new microfluidic chips for research purposes that could isolate varying characteristics contributing to inconsistent flow rates. Through systematic testing and experimentation, I generated a thorough dataset that provided a comprehensive understanding of the performance of each chip variant.
Supply Chain and Vendor Collaboration
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I played a crucial role in the efficient and seamless production of microfluidic consumables. My responsibilities were diverse and encompassed vendor management, project timeline oversight, documentation creation, and proactive problem resolution.
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I was responsible for sourcing and maintaining communication with key vendors specialized in chip pick and place, sterilization, and assembly. This involved establishing and nurturing relationships, negotiating terms, and ensuring that vendors met stringent quality and timeline requirements. Effective vendor collaboration was instrumental in achieving the desired production outcomes.
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To support the manufacturing process, I created detailed assembly instructions, pick and place wafer maps, and other essential documentation. These materials played a pivotal role in maintaining consistency, precision, and adherence to quality standards throughout the assembly line. Clear and comprehensive instructions were critical for the successful execution of each manufacturing step.
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I actively collaborated with vendors to rapidly identify and resolve problems encountered at critical project points. My ability to troubleshoot and find effective solutions in time-sensitive situations ensured that production timelines were met without compromising quality.