Novel thermoplastic microvalves based on an elastomeric cyclic olefin copolymer

Microfluidic systems combine multiple processing steps and components to perform complex assays in an autonomous fashion. To enable the integration of several bio-analytical processing steps into a single system, valving is used as a component that directs fluids and controls introduction of sample and reagents. While elastomer polydimethylsiloxane has been the material of choice for valving, it does not scale well to accommodate disposable integrated systems where inexpensive and fast production is needed. As an alternative to polydimethylsiloxane, we introduce a membrane made of thermoplastic elastomeric cyclic olefin copolymer (eCOC), that displays unique attributes for the fabrication of reliable valving. The eCOC membrane can be extruded or injection molded to allow for high scale production of inexpensive valves. Normally hydrophobic, eCOC can be activated with UV/ozone to produce a stable hydrophilic monolayer. Valves are assembled following in situ UV/ozone activation of eCOC membrane and thermoplastic valve seat and bonded by lamination at room temperature. eCOC formed strong bonding with polycarbonate (PC) and polyethylene terephthalate glycol (PETG) able to hold high fluidic pressures of 75 kPa and 350 kPa, respectively. We characterized the eCOC valves with mechanical and pneumatic actuation and found the valves could be reproducibly actuated >50 times without failure. Finally, an integrated system with eCOC valves was employed to detect minimal residual disease (MRD) from a blood sample of a pediatric acute lymphoblastic leukemia (ALL) patient. The two module integrated system evaluated MRD by affinity-selecting CD19(+) cells and enumerating leukemia cells via immunophenotyping with ALL-specific markers. We introduce cyclic olefin copolymer elastomer as a membrane layer for pneumatically or mechanically actuated microvalves using a simple bonding procedure and demonstrate its utility within a modular system for CLC isolation and immunophenotyping.