Project: Enabling large scale production of microfluidic cartridges

The present project aims at the development of a new diagnostic detection module and associated cartridges to be incorporated into the already developed Point of care technology – spinit® - to increase its comprehensiveness of test panels (incorporating a new multi parameter cartridge combining 5 part differential white blood cell counts with other different biomarkers) as well as the development of a large scale production method for the micro-fluidics cartridges. _x000D_Presently there is a range of POC devices targeting specific clinical parameters but the range of tests and type of diagnostic enabled by each device is limited. Despite the general trend for multiplexing tests, a common feature is the lack of integration of more than one type of testing in individual platforms. In this frame, combining molecular detection with cell counting capabilities in a single, easy to use, low-cost platform provides a unique product with unprecedented reach in POC testing. Blood cell counts represent the majority of tests requested in clinical practice and are in most cases combined with determination of specific molecular substances such as protein biomarkers and specific antibodies._x000D_Biosurfit's proprietary technology combines Surface Plasmon Resonance Detection with Centrifugal Microfluidics, to enable a high performance, low-cost and easy to use molecular POC testing platform (spinit®). The disposables are disk like microfluidic devices which process blood samples and selectively deliver them to reaction areas containing antibody coated surfaces. Molecular interactions occurring at these surfaces are followed in real-time by SPR imaging, enabling the quantification of specific protein markers present in blood, and within 10 minutes of its collection from a finger prick. Foreground IP will be developed on blood sample manipulation that along with optical microscopy imaging modules and associated data treatment software will enable a highly integrated POC platform, to respond to a clear unmet market need._x000D_In view of industrialization, the consortium aims to develop all required technologies for large scale production of the developed microfluidic cartridges at competitive manufacturing costs. This will be achieved building on well established mass manufacturing industries like the optical media industy, to enable high quality replication of disk based devices incorporating structural features ranging from tens of nanometers (e.g. diffraction gratings used for SPR detection) to hundreds of micrometers (required for microfluidic sample manipulation and processing). _x000D_A significant challenge are the required mechanical and optical specifications for the microfluidic cartridges._x000D_This starts with making a master with microstructures of various heights (tens to hundreds of micrometers) in optical quality (Roughness < 5nm) having draft angles on the structure walls (to enable demoulding)._x000D_Electroforming the master to produce a stamper (mould insert) requires process development because of the high structures. A flat, stress free stamper is needed. The stamper needs to have a thickness distribution < 10 micron because of opical specifications of the moulded disc (birefringence). Back finishing of this electroformed stamper is therefore needed. This is challenging because of lack of a reference surface and difficult to machine Nickel._x000D_Moulding a stress free disc with multi level micro structures is challenging. To enable optical imaging, the birefringence, optical quality (no flowlines, specs, scratches are allowed) and thickness distribution of the disk need to be within narrow specifications._x000D_The narrow specifications of the moulded disc demand accuracy from the follow in-line production steps as handling, cooling, metalizing, biofunctionalisation (depositing reagents), assembly and inspection. Low cost production requires fast cycle times which is challenging in terms of using heat and mechanical forces. The presents of reagents limits the possibility's for assembly since they don't stand heat, UV light and solvent._x000D_Present assembly technology at Biosurfit relies on multi-lamination of structured thin films and will be used at pilot level to validate processes developed at Axxicon regarding plastic substrate replication (involving mastering, tooling and injection moulding). Although this assembly technology is a valid approach for production, the consortium aims to assess and establish other assembly methods combined with adequate design changes to ease upscaling for mass manufacturing. _x000D_The design and development of the new cartridges will take into account the microfluidic functionality, optical requirements for imaging, and manufacturing aspects ranging from mastering to final assembly and packaging. _x000D_The ultimate goal is to establish the overall process work-flow in view of a self contained mass manufacturing plant capable to deliver the final product without the need for outsourcing services or product components.

Acronym	BLISK (Reference Number: 6851)
Duration	02/01/2012 - 31/12/2013
Project Topic	The present proposal aims at the development of novel lab on a disk devices capable to perform a wide variety of multiparameter blood tests for near patient diagnostics as well as the development of a large scale production method of these lab-disk devices.
Project Results (after finalisation)	The product combining cell counts and protein biomarker detection has been successfully developed. Both reader and cartridge perform according to requirement specifications. Design History File and Device Master Record have been compiled for both spinit instrument and self-contained disk cartridges and the full CE marking dossier including the results from validation studies is being submitted to the Portuguese Regulating Authorities for Medical Devices. _x000D__x000D_The devices are being manufactured at pilot level in Lisbon (Biosurfit) and use Axxicon molded substrates for both micro and nanostructured disks. _x000D__x000D_The endeavor to establish a larger scale production line at Axxicon continues and several fronts are currently being developed._x000D_
Network	Eurostars
Call	Eurostars Cut-Off 7

Project partner

Number	Name	Role	Country
2	Axxicon Moulds Eindhoven B.V.	Coordinator	Netherlands
2	Biosurfit, SA	Partner	Portugal