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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - IMPETUS (Pilot line for paper based electrochemical test strips dedicated to quantitative biosensing in liquids)

Teaser

Summary

IMPETUS will combine paper, printing and microchip technologies to realize a pilot line in an industrial environment capable of manufacturing fully integrated paper-based electrochemical biosensors that directly transfer the measured data to the userâ€™s smartphone. These biosensors will be designed as self-powered disposable test strips that combine the simplicity of lateral flow devices (LFDs) with quantitative readout, which is enabled by the implemented electrochemical detection method. As an application example, IMPETUS will fulfil the consumer need for fast and inexpensive point-of-care discrimination between bacterial and viral infections.
This goal will be achieved by developing new technologies for paper manufacturing, coating and surface modification, and the respective processing will work hand in hand with the ink development (cellulose-based inks for fabricating the printed battery as well as bio-inks for surface functionalisation and reagent deposition). A highly integrated and energy efficient silicon microchip will be developed that enables electrochemical signal acquisition, data storage and contactless NFC data transmission. The microchip will be mounted onto the paper substrate by an inline placement process. Paper will be employed as substrate for the printed circuits and the microchip, but also as active component of the printed battery as well as of the biosensor.
The IMPETUS pilot line will integrate screen-, flexo-, inkjet-printing and an unhoused chip placement in a seamless roll-to-roll process compatible with high throughput fabrication. As result, the pilot line will offer the possibility to be easily adapted for various sensing applications accessible to interested third parties after the project end.
IMPETUS is a four-year collaborative project that brings together fourteen leading partners with a strong focus on industrialisation: three research institutes (AIT Austrian Institute of Technology GmbH, Papiertechnische Stiftung, Technische UniversitÃ¤t Chemnitz), four small (Maurer Services GmbH, Maurer Engineering UG, Saralon GmbH, Pro-Active sprl) and seven large enterprises (DPI Holding GmbH, Sun Chemical Ltd., Infineon Technologies Austria AG, Melecs EWS GmbH, R-Biopharm AG, Ricoh UK Products Ltd, Felix Scholler Holding GmbH & Co KG).
In summary, the IMPETUS pilot line will pave the way towards the real world application of paper-based quantitative electrochemical diagnostic test strips, thereby clearly advancing the current state-of-the-art, which up to now has mostly focussed on individual fabrication processes and device concepts.

Work performed

The layout of the pilot line and the processing path of the paper substrate in it have been defined. The two flexo- and screen-printing unit have been successfully installed and tested using silver and carbon inks.

The in-line unpackaged-chip mounting concept has been elaborated and the actual engineering design of the chip mounting module has been realized.

At R2R laboratory level, the necessary screen- and flexographic-printing processes to realise the required paper-based components have been developed.

The base paper and its surface modification have been developed to combine suitable wicking behavior and printability. The fiber composition of the pulp was optimized to be compatible with an industrial application. Flow tests revealed that the papers developed in the project are suitable substrates for LFD fabrication.

To realise the microfluidic patterning, inks exhibiting a high and a low penetration of the paper have been developed. Screen-printing of high penetration ink on the developed paper substrates was successful to realise the 4 cm long paper-based microfluidic channels with the required liquid flow speed.

In order to realise the environmentally-friendly battery, metal-free conjugated polymer inks have been developed to realise the cathode and anode layers. The electrolyte layer based on LiCl has been realized as well.

A single microchip has been designed that contains a high-sensitive low-power CMOS sensing platform, an NFC interface for communication and power transfer, a power management for two-channel power supply, and a microcontroller that executes the NFC protocol, performs post-processing of the sensor signals and stores the measurement results.

The 1st generation biosensing system (inkjet-printed biofunctionalization on paper and external screen-printed sensor) has been realized and characterized. To this end, the two necessary protein immunoassays compatible with the electrochemical LFD have been developed. Furthermore, bio-inks to fully integrate the assay reagents in the paper matrix have been formulated to be compatible with the industrial printhead systems. Material compatibility tests on two printhead variants have been performed using the formulated inks. At S2S laboratory level, inkjet-printing of the bio-inks has been realized. Both proteins single-analyte LFDs have been demonstrated to exhibit concentration dependent signals in the targeted range.

Final results

Main results achieved beyond the state of the art and expected ones are:

- Pilot line capable of manufacturing paper-based electronics dedicated to quantitative electrochemical biosensing devices for point-of-care (PoC) applications combining flexo-, screen- and inkjet-printing in a seamless roll-to-roll (R2R) configuration.

- Inkjet printing of bio-inks and reagents has been realized at S2S laboratory level. Next step will be the transfer from the lab to industrial printhead systems.

- In-line unpackaged-chip mounting module. After the concept phase, now the implementation phase will take place.

- Paper developed with respect to the cellulose matrix and the surface to obtain suitable characteristics required for the integration of the electrodes, microchip, and the electrochemical biosensor.

- Realisation of an environmentally friendly paper-based battery. Metal-free anode, cathode, and electrolyte have been developed. Next step will be to achieve the required specifications.

- Realisation of a highly integrated and energy-efficient silicon microchip enabling biosensor measurements, data acquisition, data storage as well as secure near field communication (NFC) data transmission. After the development phase, now the fabrication will take place.

- Realisation of a printed electrochemical LFD for quantitative measurement of two biomolecule concentrations in blood allowing the differentiation of bacterial from viral infections. The 1st generation biosensing system has already been realized.

Potential impacts are:

- Pilot line with a versatile manufacturing concept easy to be adapted for various sensing applications (e.g. health care, veterinary diagnostics, food safety, environmental monitoring).

- The showcase application targeted by the biosensing system is to distinguish viral from bacterial infections to decrease the incorrect diagnosis and false medication of viral infections by antibiotics during initial treatment.

- By providing inexpensive and fast quantitative readout of selected application-specific biomarkers, the IMPETUS biosensing system will open up molecular testing to numerous applications in manifold areas such as medical diagnostics, drug monitoring, veterinary diagnostics, food safety or environmental monitoring.