title: A portable and reconfigurable multi-organ platform for drug development with onboard microfluidic flow control.
abstract: The drug development pipeline is severely limited by a lack of reliable tools for prediction of human clinical safety and efficacy profiles for compounds at the pre-clinical stage. Here we present the design and implementation of a platform technology comprising multiple human cell-based tissue models in a portable and reconfigurable format that supports individual organ function and crosstalk for periods of up to several weeks. Organ perfusion and crosstalk are enabled by a precision flow control technology based on electromagnetic actuators embedded in an arrayed format on a microfluidic platform. We demonstrate two parallel circuits of connected airway and liver modules on a platform containing 62 electromagnetic microactuators, with precise and controlled flow rates as well as functional biological metrics over a two week time course. Technical advancements enabled by this platform include the use of non-sorptive construction materials, enhanced scalability, portability, flow control, and usability relative to conventional flow control modes (such as capillary action, pressure heads, or pneumatic air lines), and a reconfigurable and modular organ model format with common fluidic port architecture. We demonstrate stable biological function for multiple pairs of airway-liver models for periods of 2 weeks in the platform, with precise control over fluid levels, temperature, flow rate and oxygenation in order to support relevant use cases involving drug toxicity, efficacy testing, and organ-organ interaction.
authors.affiliation: Materials and Microfabrication Directorate, Draper, Cambridge, MA 02139, USA. jborenstein@draper.com.
authors.forename: J R
authors.initials: JR
authors.lastname: Coppeta
authors.affiliation: Materials and Microfabrication Directorate, Draper, Cambridge, MA 02139, USA. jborenstein@draper.com.
authors.forename: M J
authors.initials: MJ
authors.lastname: Mescher
authors.affiliation: Materials and Microfabrication Directorate, Draper, Cambridge, MA 02139, USA. jborenstein@draper.com.
authors.forename: B C
authors.initials: BC
authors.lastname: Isenberg
authors.affiliation: Materials and Microfabrication Directorate, Draper, Cambridge, MA 02139, USA. jborenstein@draper.com.
authors.forename: A J
authors.initials: AJ
authors.lastname: Spencer
authors.affiliation: Materials and Microfabrication Directorate, Draper, Cambridge, MA 02139, USA. jborenstein@draper.com.
authors.forename: E S
authors.initials: ES
authors.lastname: Kim
authors.affiliation: Materials and Microfabrication Directorate, Draper, Cambridge, MA 02139, USA. jborenstein@draper.com.
authors.forename: A R
authors.initials: AR
authors.lastname: Lever
authors.affiliation: Materials and Microfabrication Directorate, Draper, Cambridge, MA 02139, USA. jborenstein@draper.com.
authors.forename: T J
authors.initials: TJ
authors.lastname: Mulhern
authors.affiliation: Materials and Microfabrication Directorate, Draper, Cambridge, MA 02139, USA. jborenstein@draper.com.
authors.forename: R
authors.initials: R
authors.lastname: Prantil-Baun
authors.affiliation: Materials and Microfabrication Directorate, Draper, Cambridge, MA 02139, USA. jborenstein@draper.com.
authors.forename: J C
authors.initials: JC
authors.lastname: Comolli
authors.affiliation: Materials and Microfabrication Directorate, Draper, Cambridge, MA 02139, USA. jborenstein@draper.com.
authors.forename: J T
authors.initials: JT
authors.lastname: Borenstein
mesh_terms: D001980:Bronchi / Q000166:cytology; D002478:Cells, Cultured; D018920:Coculture Techniques; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D055808:Drug Discovery; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D060526:Magnetic Fields; D044085:Microfluidics / Q000295:instrumentation / Q000379:methods*; D008856:Microscopy, Fluorescence
chemical_list: D051544:Cytochrome P-450 CYP3A