Case Study: Oligonucleotide Synthesis Process Scale-up

Client Organization: Life Sciences Startup
Business Terms: Time & Material
Anticipated / Actual Engagement Duration: Indefinite / 8 months
Service Location: On-site at client's facility, Seattle Area
Client Objective(s): Design and implement a synthesis process incorporating the client's proprietary protocols and trade-secret consumables.
Challenges: The biological reagents used in oligo synthesis are extremely corrosive and extremely expensive. Aforementioned reagent distribution to >100 solenoid valves.Reagent distribution and replenishment must support a continuous process (replenish without disrupting the synthesis process).The synthesis process is complex, time-consuming, and must be executed in a dry atmosphere.The quality requirements for gene synthesis grade oligos are very high; the process must be robust and reliable.The synthesis instrument must run unattended for extended periods of time.The client, a biotech startup with little experience in capital equipment development, was trying to secure investment funding from one of their large customers. The technical stakeholders were interested in investing; however, the financial management stakeholders were reluctant to release funding without substantial planning documentation.
Implementation Strategy: Draft and submit comprehensive project and technical management planning documentation to the customer organization, to secure the release of investment funding. Design a high throughput process based on client synthesis protocol. Design and build a high throughput synthesis instrument to execute process. Synthesize 20 to 150 mer Oligos at 1 to 5 nmol scale, with a daily throughput target of 500 k to 1 M bases. Dispenses reagents on the fly, into a 384 well microtiter plate. Develop and implement comprehensive quality assurance methods to monitor the synthesis process.
Outcome: The instrument was built, and software was being developed when the client went out of business. Ultimately, the IP was acquired by another company and the development effort was resumed under different leadership.

Case Study: Drug Delivery Device Design, Build, & Deploy

Client Organization: Biotech / Pharmaceutical R&D Company
Business Terms: Time & Material
Anticipated / Actual Engagement Duration: Indefinite / 1 Year
Service Location: Primarily off-site
Client Objective(s): Design and build a hand-held device to implement the client's proprietary drug delivery technique, in humans, in a clinical setting.
Challenges: The prototype drug delivery process / apparatus incorporated multiple disparate elements, under the coordination of a research technician, in a laboratory setting. For the human trials, clinicians would need to operate the system in a clinical setting, with reasonable training on the system and process.The hand held device would need to be capable of coordinating motion and the discharge rate of multiple therapeutics, without consuming electricity.The discharge volumes are measured in microliters. The acceptable window of deviation from the prescribed dosage is narrow. Multiple therapeutics would need to be loaded into the device, in a very small area. Necessary features of the device interfere with traditional drug preparation and loading techniques.Incorporate multiple Closed System Transfer Devices into the system, to facilitate loading the therapeutics. Develop the protocols and logistics associated with manufacturing an experimental device; cleaning, sterilizing, and packaging a medical device with multiple elements; maintaining sterility of the various elements throughout the device preparation and therapeutic loading phase, until the procedure is administered at the point of care. Implementation Strategy: Develop an understanding of the existent system. Thoroughly and clearly define the solution space through exhaustive discussions with the principal investigators. Creatively apply 1st principles of micro-fluidics to solve the challenges associated with accurately loading and discharging therapeutics to / from the hand-held device. Creatively apply 1st principles of tool-making, material science, and ergonomics, to incorporate the required functionality into a hand-held device, roughly the size of a dry-erase marker.
Outcome: A system was developed in less under 12 months. The system was patented, and has been put into service.

Case Study: Deploying Large Composite Layup Systems

Client Organization: Large Commercial Aviation & Defense Company
Business Terms: Time & Material
Anticipated / Actual Engagement Duration: 1 Year / 2.5 Years
Service Location: End user's facility in Japan
Client Objective(s): Enable the maintenance and operation of a very large and complex system-of-systems. Train end users in troubleshooting methods, performing root cause analysis, and facilitating repairs & improvements. Act as an intermediary between the machine manufacturer, discipline experts, and the technical stakeholders of the end user organization, in order to facilitate the transition of responsibility for troubleshooting and maintenance of the system from the manufacturer to the end user organization. Challenges: A complex topology of stakeholders with disparate, and occasionally conflicting, objectives.16 hours time difference between end user location and the location of machine manufacturer / discipline experts. The geographic and cultural distance between two countries that are 16 hours apart. Effectively interfacing with the end user organization, whose members are distributed over a broad spectrum of cultural / philosophical refinement and regard of foreigners. The language barrier. The end user facility is operational 24 hours a day; machine malfunction or operator error can occur at any time while the machine is in operation. Up-time is very valuable; down-time is very costly. High pressure and high visibility of the installation / commissioning / validation phases of this effort, due to the human & organizational dynamics between the end user, the machine manufacturer, and the sole customer of the entire facility. The innumerable technical challenges concomitant with such a large and complex system-of-systems. All forms of fatigue experienced by all of the stakeholders over such a lengthy process.
Implementation Strategy: Never give up.
Outcome: Multiple systems were validated and put into production of primary structural components of a commercial aircraft. The end user took ownership, both literally and figuratively, of the systems, and would eventually add to the number of systems in that facility.

Case Study: Assembly Automation for Very Small Components

Client Organization: R&D Arm of a Mixed Reality Device Startup Company
Business Terms: Time & Material
Anticipated / Actual Engagement Duration: Indefinite / 1.25 years
Service Location: GTI Facility
Client Objective(s): Demonstrate ways and means of automating the production of very small electro-optic assemblies. Develop proof-of-concept production methods and equipment in parallel with product development. Challenges: The constituent elements are very small. (Outside dimensions are sub-millimeter) The constituent elements are very delicate. (glass and ceramic)The process requires extreme accuracy and precision of constituent element registration, motion control, and dispensing of fluid. Overcoming the effects of surface tension and controlling the wetted area of a very small workpiece. Environmental & process cleanliness requirements; features that effectively register small components are also effective at trapping contaminants and detritus shed from the product / process.
Implementation Strategy: Apply first principles of production automation and tooling design to layout a viable production process.Apply first principles of machine design to build a very stiff, repeatable, and appropriately dynamic system. Apply tool & die maker trade knowledge to select tooling materials and fabrication processes to produce high precision tooling and mechanism.
Outcome: Prototype tooling was designed and manufactured. A liquid metering and application method was under development. The client reorganized and defunded their R&D efforts.

Case Study: Ground Support Equipment

Client Organization: Satellite Payload Integrator
Business Terms: Time & Material
Anticipated / Actual Engagement Duration: Indefinite / 16 months
Service Location: GTI Facility
Client Objective(s): Automate the cleaning and metrology of material to be incorporated into a satellite payload. Challenges: Space is hard. A chain is only as strong as its weakest link. The recognition of these principles in space craft development leads to very low tolerance of risk. Raw materials to be incorporated into a space flight payload must be thoroughly cleaned and measured. The measurement data should be preserved and documented within the systems engineering framework through which the spacecraft is being developed. Human error in cleaning, measuring, and recording data should be avoided.The material processing system should run unattended, have high reliability, and high availability. The system must generate and store data products containing upwards of 27,500 measurements per production cycle. The system must export the data product(s) from the industrial supervisory controller to a PC / Mac.Facilitate packaging of the processed & measured material in a clean environment, while preventing the re-introduction of contaminants. (The system operates in an uncontrolled / unconditioned environment, so ambient air quality would re-contaminate the processed material.)The data product would be used to inform the design of other payload elements; thus, the prioritization of system capabilities was fluid.
Implementation Strategy: Apply first principles of process automation to design to rapidly prototype a 1st gen automated metrology instrument. The 1st gen solution was built and generating data products in less than a month. Apply first principles of process automation, machine design, metrology, and critical cleaning to design and build a 2nd gen processing system in two phases.Due to severe time constraints, Phase 1 of the Gen-2 system development effort would incorporate only the necessary elements to generate metrology data products, which were gating the clients payload design and integration effort.Following the data product delivery milestone, the Phase 2 of the Gen-2 system development effort would realize the completion of the other processing functionalities.
Outcome: In total, QTY(3) systems were designed, built, and operated in the GTI facility. Data product and processed material were completed and packaged on-site at GTI, and the equipment was later delivered to the client.