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Nano cellulose based paper diagnostic devices

Final Report Summary - NANOPAD (Nano cellulose based paper diagnostic devices)

Background
Diagnosis of number of diseases (such as HIV, antibiotic resistant bacteria), monitoring of of health markers (e.g. blood values) or environmental monitoring (e.g. water quality) rely today mostly on centralized laboratories with specialized instruments and skilled personnel. This type of clinical analysis with long lead times and high cost is inappropriate for point of care (POC) diagnostics (e.g. at homes, or in rural clinics). One proposed solution has been the use of paper, and printing technologies as a means for realizing advanced POC devices. The underlying idea is that paper and other cellulose based materials can be turned into complete miniature laboratories (Lab on paper) that can perform analytical tests and return the results by optical or electrical means. By translating paper and printing technologies to laboratories the cost of manufacturing can be drastically reduced.

The main goals of this program have been to further develop the materials, methods, and techniques that rely on paper and cellulose based materials to achieve diagnostic devices that are advanced, yet disposable (almost zero-cost). More specifically this project aimed at:
1. Exploring the use of conducting polymers, (or other electrical inks), to turn the surface of paper into electrical and electrochemical devices, and thereby monolithically integrate electronic function into the Lab on paper.
2. Exploring the use of cellulose based materials, other than paper, to achieve analytical functions.

Main results of this project
Unification of printed electronics and printed microfluidics
We have developed techniques for co-fabrication of paper electronics and microfluidics using only printing. This technique allows the micropatterning of porous electronic conductors in paper that are different from conventional printed wires, since they are porous with a high surface area, can transport both electrons and liquids at the same time, and are stable to scratch and creasing of the paper. Using this manufacturing technique, we have demonstrated several features: i) printed circuit boards in complex geometries, ii) Electrochemical paper devices that can perform a number of assays inside of paper with a high precision, and iii) foldable paper based batteries for storing electrical energy inside paper, and releasing this energy upon the application of electrolytes.

The microfabrication of conducting polymers inside paper, also enabled the development of a class of actuators that we name Hygroexpansive Electrothermal Actuators HEPAs. They operate based on reversible the ability of paper to change dimensions based on its water content (hygroexpansion). We showed that HEPAs can be used for making paper based micro machines with advanced shape, and function. Such machines can enable a set of the function that the much more advanced MEMS structures perform today.

Using the porous conductors in paper (and other porous materials), we have also developed the first printed electrical valve that can control the flow of liquids. This valve operates rapidly, and is chemically robust. The key component of the valve is a hydrophobic, conducting porous mesh (mainly woven textiles) which acts as a liquid barrier. Application of a high voltage between the liquid and the mesh, results in electrowetting and penetration of the liquids through the barrier (the valve opens). These valves are a key component for the realization of autonomous electrical Labs on paper.

Cellulose microfluidics
To explore cellulose as a material for microfluidics we developed a method for manufacturing microfluidic devices made completely from cellulose polymers by embossing micro channels into cellophane a cellulose based film. These demonstrations represent the first steps towards all cellulose based open channel microfluidic devices. The biocompatibility, solvent resistance, and excellent optical transparency of cellulose (especially in deep UV), make this material an interesting candidate for replacing plastics and quartz glass in future microfluidic applications.

Ion sensors integrated in paper
Potentiometric ion sensing is based on the combination of ion selective membranes ISM, and electrochemical working and reference electrodes. These sensors can be used for the detection of the concentration of numerous specific ions in biological as well as environmental samples. Today the cost and size of potentiometric ion sensors limit their use. We explored paper as the platform for total integration of a potentiometric ion sensors. By printing sensing electrodes, fluidic channels, and reference electrodes on the paper, and also integrating an ISM membrane in the paper device, we showed that it is possible to realize a complete paper based ion sensor. These sensors are very cheap and portable and can be used as disposable devices in many applications, ranging from analysis of ions levels in blood to monitoring of water quality.


Impact
The efforts to combine the fields of electronics and microfluidics has enabled the design and creation of batteries, electrical fluid valves and electroanalytical devices, that can be all integrated using printing and paper. These techniques present a new platform for realizing a range of micro total analysis system using paper and printing.

The realization of Ion sensors on paper open the avenue to explore printed ion sensors for a range of applications, and with improved designs that allow more robust and user-friendly ion sensing.

These techniques have been patented, through Harvard patent office with five patent applications, and to the best of our knowledge these patents are a part of a portfolio that is used for non-profit purposes to enable diagnosis and health monitoring to the developing world (e.g. through a company called diagnostics for all, or other start-ups).

A more indirect impact of this work is that it extends the field of printed electronics to include more advanced functions on paper, thus extending the promise using paper as one main substrate for the future of internet of things.