Personalized, cell-based therapies and personalized drug selection constitute two important facets of precision medicine, treatments specifically tailored to the individual receiving them.
Draper’s Biomedical Solutions capability centers on the application of microsystems, miniaturized electronics, computational modeling, algorithm development and image and data analytics applied to a range of challenges in healthcare and related fields. Draper fills that critical engineering niche that is required to take research or critical requirements and prototype or manufacture realizable solutions. Some specific examples are MEMS, microfluidics and nanostructuring applied to the development of wearable and implantable medical devices, organ-assist devices and drug-delivery systems. Novel neural interfaces for prosthetics and for treatment of neurological conditions are being realized through a combination of integrated miniaturized electronics and microfabrication technologies.
Draper continues to develop its expertise in designing, characterizing and processing materials at the macro-, micro- and nanoscales. Understanding the physical properties and behaviors of materials at these various scales is vital to exploit them successfully in designing components or systems. This enables the development and integration of biomaterials, 3D printing and additive manufacturing, wafer fabrication, chemical and electrochemical materials and structural materials for application to system-level solutions required of government and commercial sponsors.
Draper has designed and developed microelectronic components and systems going back to the mid-1980s. Our integrated, ultra-high density (iUHD) modules of heterogeneous components feature system functionality in the smallest form factor possible through integration of commercial-off-the-shelf (COTS) technology with Draper-developed custom packaging and interconnect technology. Draper continues to pioneer custom Microelectromechanical Systems (MEMS), Application-Specific Integrated Circuits (ASICs) and custom radio frequency components for both commercial (microfluidic platforms organ assist, drug development, etc.) and government (miniaturized data collection, new sensors, Micro-sats, etc.) applications. Draper features a complete in-house iUHD and MEMS fabrication capability and has existing relationships with many other MEMS and microelectronics fabrication facilities.
For companies in need of more-effective cell therapy processing solutions and drug selection options, Draper’s extensive experience and expertise in biology, microfluidics, system integration and subsystem maturity can be applied to designing closed systems; automated, standardized processes; end-to-end solutions; continuous processing; and scalable solutions. These improvements to processes and technologies can help pharmaceutical companies solve the engineering challenges of production to achieve the cost reductions, accelerated results, reduced risk and increased safety that they need to make precision medicine practical.
Improving the Manufacturability of Cell-based Therapies
As pharmaceutical companies pursue the promise of cell therapies to provide precision medicine, they confront a number of barriers in production, including cost, time and quality management. Draper is helping to enable the production of successful cell therapies by designing and developing innovative custom systems for cell therapy manufacturing.
Robust manufacturing processes are critical to the success of cell-based therapies. With more than 400 cell therapy clinical trials currently underway, promising candidates are moving toward the commercial market. The production of these powerful treatments must be standardized, scaled and automated to enable them to be produced efficiently, safely and at a reasonable cost. To this end, Draper is designing and developing modular microfluidic devices that ultimately can be linked to carry out the entire multistep cell therapy manufacturing process.
Currently Draper is focusing on improving the technology for manufacturing CAR T-cell therapies, cutting-edge treatments consisting of immune system cells that have been genetically modified to specifically recognize and kill cancer cells. Devices are in development for two key process steps: cell separation and gene transfer. Through the use of microfluidics, precise control of cells, conditions and microenvironments will be possible.
To perform cell separation Draper has developed a microfluidic acoustophoresis technology for lymphocyte purification. This solution uses ultrasonic energy to excite cells in a blood sample as it flows through microchannels, causing different types to separate from each other rapidly and continuously. This system routes the lymphocytes into designated outlet channels and sends other cell types into a different channel in the system. Draper has designed the device using plastic so that it can be a low-cost disposable suitable for high-volume manufacturing.
Testing the system with leukapheresis product, Draper’s approach achieved 94% lymphocyte purity (as a fraction of other white blood cells). Draper continues its efforts to enhance the system’s performance.
To improve the transduction process, Draper is developing a microfluidic device to reduce the amount of viral vector required to carry a therapeutic gene into the target cell’s nucleus. Draper’s technology also should reduce the length of the transduction process to under one day, versus the typical one to three days of the current method. In initial experiments, Draper’s technology has demonstrated transduction efficiencies comparable to those of centrifugation, the current gold standard.
It will be possible to integrate the cell separation and transduction devices into an end-to-end system that performs the entire manufacturing process. Advantages of a closed, end-to-end system include automation to minimize human error and enable standardization, as well as reduction of the risk of contamination. Using its expertise in sensor technology, Draper plans to integrate sensors into the modules and system for real-time measurements; by monitoring the process, sensors will provide data to enable real-time surveillance and adjustments to the operating conditions. The system will enable efficient, high-quality and cost-effective bioprocessing of cell therapies—a benefit to manufacturers, clinicians and patients.
Differentiating Stem Cells for Precision Medicine
For producing cell therapies and for drug discovery, the best currently available resource is primary human tissue because it is the most functional; however, the supply of donated human tissue is insufficient to meet the needs for current patient treatment or medical research. The ability of stem cells to become specific cell types that then can grow into highly functional human tissue has brought stem cells to the fore as a potential alternative source of human tissue for developing and producing cell therapies. In addition, because stem cells are self-renewing, their supply is theoretically unlimited. The ability to generate healthy human tissue as needed could significantly increase the development of therapeutic solutions for everyone.
To enable the production of specific types of tissue as needed by researchers or clinicians, Draper is developing technology to turn adult or induced pluripotent stem cells into specific cell types. Draper’s process can use stem cells from many donors, capturing genetic population diversity, or from an individual to customize drug therapies.
Draper’s approach is to combine advanced tissue engineering techniques with automation and noninvasive sensor feedback to optimize the microenvironment for differentiating stem cells into a target tissue. Since each tissue type requires a unique environment, a modular tissue-specific microfluidically perfused tissue cassette is designed to control the biophysical cues that affect cell phenotype. Factors including cell-materials interaction, microfluidics shear and transport of soluble factors, the local gas composition, 3-D tissue patterning and cell-cell interactions are controlled to guide cell phenotype. By monitoring cellular response to these biophysical cues using noninvasive sensors, a deeper understanding of the cellular dynamics leading to high-fidelity tissue formation is possible and the microenvironment can be optimized accordingly.
In collaboration with Dr. David Scadden at Harvard Stem Cell Institute, Draper is pursuing an early clinical application of this research for leukemia patients. This treatment could reconstitute quickly a patient’s immune system after a bone marrow transplant by providing healthy immune cells derived from stem cells.
Ex Vivo Immuno-oncology Dynamic ENvironment for Tumor biopsies (EVIDENT)
While many therapies are available to treat cancer, it’s typically not known in advance how well a particular drug will work on an individual patient's cancer. To help doctors select the best available treatment for their patients, Draper is applying its expertise in microfluidic disease models to create a multiplex tumor microenvironment platform for evaluating the efficacy of cancer drugs directly on patient samples.
Called Ex Vivo Immuno-oncology Dynamic ENvironment for Tumor biopsies (EVIDENT), the system mimics conditions in the human body, providing a microenvironment to sustain tumor samples. A precision-controlled microfluidic system delivers various drugs or combinations of drugs to cancer samples to determine quickly which is most effective in killing that patient’s cancer. This microfluidic system tests treatments on cancer cells directly from the patient, without putting the patient through each treatment. Because EVIDENT can incorporate circulating immune cells from individual patients in the microfluidic system, it also can test the effectiveness of immunotherapy drugs, which unleash the body’s own immune system to fight cancer.
With the help of EVIDENT , patients’ initial treatments will likely be the best option—without subjecting their bodies to a potentially life-threatening trial-and-error process.