Current changes in the population pyramid of developed contries requires a new paradigm in the health care systems. Paper is a renewable resource that it can be produced even in developing countries and therefore it has a potential for improving and spreading healthcare even in resource-limited areas.
According to World Health Organization (WHO), Paper has the potential to develop diagnostic devices that can be Affordable, Sensitive, Specific, User-friendly, Robust, Equipment-free and Delivered to end-user ("ASSURED"). From the health care politics, “ASSR" characteristics are basic for development of low-cost sensors; but the "U" (user-friendliness) is key when there is a need for empowering the patient.
To achieve these needs this proposal focuses on improving compatibility of printed electronics with microfluidic assays to increase the intelligence of these devices and their friendliness to the end-users with the maximum sensitivity and specificity. Integrated electronics on microfluidic-based devices will provide easy-to-understand results, lower the assay operation.
To achieve this goal paper is the key component, since paper properties such as porosity, liquid wicking rate, fiber surface affinity to different analytes can be modified to adapt to the defined assay. Besides paper is foldable and can be fabricated into 2D and 3D devices using the traditional craft of origami, or simply using sticky tape to form layered paper structures for microfluidics.
In this project, Paper is manufactured to create diagnostic devices designed to perform the same tasks an ELISA and/or nucleic acid assays, which may require multisteps with different analytes, reagents and reaction times. This means design of fluidic pumps, fluidic resistors, mixers, valves, filters and other fluidic elements on paper.
One of the characteristics of μPADs is that patterns defining flow channels enable multiple assays on a single device. Most of current μPADs selected commercial Whatman filter papers.There is a lack of study of the use of different paper propierties to improve the performance of the assay and the compatibility with paper electronics. Paper structure design can be modified through processes of papermaking, paper coating, and printing.
Treating the paper with different materials can also control the velocity of liquid transport. This vertical transport allows the interaction with different types of papers suitable for interaction with biomolecules or printed electronics.
The control of wetting conditions of paper makes it possible to design liquid transport pathways on paper without the requirement of external liquid pumping systems. In this project cellulose hydrogel will be obtained from different cellulosic fibers (wood and non-wood) and/or nanocellulose, in order to evaluate their use as a flow controller. The advantages of these hydrogels are their non-toxicity, biocompatibility and biodegradability.
Another critical aspect of μPADs is the readout of results, which needs to be as simple and clear as possible to users. Most of current devices use colorimetric detection techniques, which is simple; but the sensitivity usually does not meet the requirements of current biological and clinical analyses. This project integrates other biosensing techniques such as impedance based spectroscopy or other electronic strategies that could avoid the dependency on external equipment such as scanners and cameras and avoid calibration. To achieve this goal, formulations based on nanocellulose will be tested for priming coatings of the standard paper substrates to achieve moisture stability and required surface roughness.
Paper structure design through processes of papermaking
Papermaking can modify internal paper structure and this enhances the performance of the designed assays. MicroTech Lab from Universitat Politècnica de Catalunya has been previously working in paper-based blood typing devices1, where RBC filtration property has to be tuned through paper properties to a specific size range, i.e., single cell vs cell clusters.
In this project different cellulose fiber of different dimensions, manufacturing different refining degrees and basis weights will be tested to manufacture paper with improved the performance for blood typing assays. The refining is an energy extensive process; therefore, a cellulase enzymatic treatment before the refining will be tested in order to decrease the energy consumption of this mechanical treatment. Moreover, the enzymatic treatment modifies the fiber surface, which could affect positively some properties like density and porosity.
FUNDING: This project if funded by Spanish Ministry of Science and Economy CTQ2017-84966-C2-1-R
1.-J Casals-Terré, J Farré-Lladós, A Zuñiga, MB Roncero, T Vidal REPlicating RAPid Microfluidics: Self-Replicating Printer for Hydrophobic Pattern Deposition 3D Printing and Additive Manufacturing, 2017 4 (4), 231-238
2.- J Casals‐Terré, J Farré‐Lladós, A Zuñiga, MB Roncero, T Vidal Novel applications of nonwood cellulose for blood typing assays. J Biomed Mater Res B Appl Biomater. 2019 Jul;107(5):1533-1541. doi: 10.1002/jbm.b.34245. Epub 2018 Oct 3.
3.- J Casals‐Terré, J Farré‐Lladós, Joan A. López, T Vidal, MB Roncero Enhanced fully cellulose based forward and reverse blood typing assay Journal of Biomedical Materials Research Part B: Applied Biomaterials. May 2019 doi.org/10.1002/jbm.b.34400