Using bioprocessing equipment intended for research to manufacture complex immunotherapies contributes to a single treatment costing hundreds of thousands of dollars and taking weeks to prepare. To produce high-quality therapy quickly and affordably, technology must be standardized, scalable to volume production and automated. Draper is working to give more patients access to this life-saving therapy by developing a modular, closed, end-to-end bioprocessing system capable of processing billions of cells in hours — enough to produce a treatment in a single, standard work shift.

Draper’s system uses advanced techniques, including acoustophoresis (ultrasonics) and high-precision microfluidics for label-free cell selection, in-line cell washing and rapid gene delivery. The modular devices enable both established viral transduction methods for production of autologous therapies or next-generation processing of allogenic therapies using electrotransfection. This scalable, closed end-to-end bioprocessing system can process a range of blood products (e.g., whole blood, apheresed material, frozen or fresh solutions, etc.), cell types, donor sources and genetic material.

Developed for clinical use, Draper’s complete end-to-end bioprocessing system for cellular immunotherapies uses innovative approaches, such as high-precision microfluidics to perform cell separation, gene delivery and in-line washing, to give more patients access to this life-saving technology.

Using sonic waves for cell separation

To accomplish cell separation on a clinical blood sample, instead of using centrifugation Draper’s system performs acoustophoresis in a high-performance microfluidic device compatible with a wide range of patient materials and input volumes. The module continuously and rapidly removes interfering cell contaminants without compromising cell health. With less handling than conventional approaches, acoustophoresis improves end-to-end yield of cells — especially in patients with low T-cell counts — and accelerates delivery to downstream steps in the process.

Gene delivery in cells

To manufacture therapies, genetic materials are introduced into a patient’s acoustically separated cells. Draper has developed two gene delivery platforms:

• A transduction module that uses viral vector more efficiently (e.g., lentivirus, retrovirus, AAV).
• An electrotransfection module that electroporates patient cells rapidly and continuously (e.g., mRNA, DNA, transposons).

Transduction

Draper’s microfluidic transduction module increases speed and efficiency. Using gentle, controlled fluid flow, it can co-localize viral vector around cells, increasing viral-cell interaction, while using about half the viral vector typically needed to achieve high transduction efficiency. Draper’s system can transduce at standard efficiency levels in 90 minutes using a wide range of vector sources.

Electrotransfection (electroporation)

Draper has engineered a practical continuous-flow electroporation module and in-line buffer exchanger that uses high-precision microfluidics to tightly control cells’ exposure to electrical current, increase throughput, reduce manual touch labor and allow for in-line wash steps. This transfection method increases efficiency of cell modification, minimizes cell death and processes many cells quickly — over one billion in minutes using a single microfluidic channel, which traditionally takes hours with significant touch labor. This technology can be parallelized to meet throughput needs of virtually any scale.

Draper’s closed, automated system will reduce sample contamination risks, leading to fewer rejected products and more successfully produced therapies. The modular system can be deployed at the point of care in local hospitals, reducing manufacturing costs and time, expanding patient access to revolutionary cell and gene therapies — ultimately saving more lives by getting therapies to patients faster.

Draper’s electroporation technologies also can be adapted to take advantage of emerging gene editing tools, expanding the capabilities of these therapies to the eradication of solid tumor cancers and eventually toward off-the-shelf cellular therapies rather than patient-specific therapies.