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Inkjet printing technology is driving innovation of sensors for point-of-care devices

Miguel Zea, researcher at GAB Group –  Nanbiosis U8 Micro– Nano Technology Unit  will defend hir PhD thesis on Friday 23 of July, at 11 am, at the Graus Room of the Faculty of Sciences and Biosciences of the UAB about “Inkjet printing technology is driving the innovation of sensors for point-of-care devices”

Thesis directors: Gemma Gabriel and Eloi Ramon

Further information and registration for the event, onñine, here

Abstract: 

The ‘Inkjet printing’ technology is called to be the next generation of flexible electronics capable of performing functions that were only accessible with state-of-the-art microfabrication technologies. This is due, in part, to the versatility of digital, non-contact patterning techniques but also to the substantial investment in research and development for inkjet printing of functional materials in recent years. Inkjet printing is an additive manufacturing technology based on the contact-less deposition of micro-droplets of a functional material with micrometer precision on the desired substrate area, through a digital design. Moreover, inkjet printing is capable of modifying the printing pattern in real time. Consequently, design changes can be introduced without any additional costs, allowing to create personalized designs with unique features. Nowadays, industrial inkjet printing has reached high standards of flexible, robust, and reliable performances.

The consensus is that inkjet printing will facilitate the production of flexible electronics in a cost-effective, on circular-economy, and reducing waste manner, enabling the development of currently unavailable wearable and disposable devices. This is the point at which Point-of-Care testing devices (PoCT) enter in the equation due to their importance in medical trails. These devices are defined as medical diagnostic testing at or near the patient. PoCT devices rely on a fast and accurate measurement based on sensors that provide the physician with a set of important data to make a diagnosis. However, major limitations of state-of-the-art PoCT devices include cost, disposability, biodegradability, and reliability. Inkjet printing technology offers solutions to address these problems where its great promises are low-cost, non-contact, rapid prototyping, material varieties, and wide range of substrates. Moreover, in the last 15 years, this technology has already shown its potential in the fabrication of reliable and quantitative sensors which form the essential components of PoCT devices. However, our understanding of the technology and its capabilities are still in a promising or potential stage, and further expertise needs to be acquired to facilitate the development of complete fully printed PoCT devices.

Identifying these problems and possible solutions, this thesis focuses on showing the potential of inkjet printing to develop sensors on flexible plastic substrates and porous paper, challenging technology to its current limit. The first part addresses the formulation, printing, and characterization of new functional inks that allow us to obtain new conductive inks to be used in the area of sensing analytes of interest. On flexible plastic, two potentiometric pH sensors have been developed. The first shows the importance of the intrinsic roughness property of a new platinum ink based on nanoparticles to provide mechanical stability to iridium oxide, a pH-sensitive material, grown electrochemically on it. For this purpose, a pH sensor was developed using the new Pt ink and the stability over a year of this iridium oxide layer was studied, which showed a clear improvement in its performance. The second pH sensor goes one step further and is, to date, the first pH sensor entirely fabricated by inkjet printing. To meet this objective, a new polymeric ink was formulated composed of a mixture of polypyrrole and pH-sensitive polyaniline. This ink was printed on a previously printed gold microelectrode and, to finally obtain a fully printed pH sensor, the fabrication was completed with a printed silver/silver chloride pseudo-reference electrode. The second part addresses the challenge of printing a sensor on a more eco-sustainable substrate such as paper, an important factor for disposable PoCs. On any paper substrate, the difficulty in printing is greater due to the porosity, delicacy, and hydrophilicity of this material. In a first work, the challenge of printing conductive functional inks such as gold or silver, and dielectric inks such as SU8 on the substrate in an efficient and easy-to-reproduce way to obtain an electrochemical sensor is addressed. The printing of a new hydrophobic ink that allows to selectively block the area of the paper where the printing of the conductive inks that make up the electrochemical sensor will be required is proposed and studied. Finally, in a second work, a cortisol immunosensor was implemented on these sensors printed on a paper substrate and its response was characterized and compared with other reported sensors, demonstrating the good performance of this technology in the detection of biological target molecules in biological samples.

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Three Nanbiosis units work in the development of new sensors for the better detection of the fungus P. jirovecii, responsible for Pneumocystis pneumonia

Researchers from the CIBER-BBN have succeeded in developing detection systems for Pneumocystis jirovecii, an atypical fungus responsible for very serious pneumonia in immunosuppressed patients. These results, published in the journal Nanomaterials, are the result of collaboration between the CIBER-BBN groups led by Laura Lechuga, Ramon Eritja and Ramón Martínez Máñez, and the CIBERESP group led by Enrique J. Calderón.

The researchers acknowledge the paricipation of three NANBIOSIS units of CIBER-BBN:

The detection of the fungus in patients, who may be asymptomatic carriers until they develop pneumonia, is currently carried out using the PCR technique, requiring several hours, adequate facilities and qualified personnel to detect it. Now, the application of Nanotechnology has allowed the development of more sensitive and efficient biosensors to detect specific sequences corresponding to pathogens responsible for infectious diseases in a shorter time and without the need for large infrastructures.

In this case, a specific sequence corresponding to the gene belonging to the ribosomal subunit (mtLSU rRNA) of the P. jirovecii fungus has been detected using hairpin-shaped capture probes. These specific probes, as pointed out by Dr. Aviñó, a researcher at CIBER-BBN at the IQAC-CSIC, “are more efficient and are capable of recognizing a specific genomic sequence of the fungus and forming very stable triplex structures that can be detected on different platforms. biosensor “.

Laura Lechuga’s team at ICN2, through the use of an optical biosensor based on SPR technology, has detected in real time and without the use of markers, P. jirovecii in bronchoalveolar lavages and nasopharyngeal aspirates with a detection limit of nM level and in just a few minutes.

Likewise, the group led by Ramón Martínez-Máñez, scientific director of CIBER-BBN and principal investigator of the IQMA-IDM group at the Universitat Politècnica de València, has used the strategy of molecular gates composed of an anodic albumin matrix to develop a sensor capable of to efficiently detect real P. jirovecii samples without previous amplification steps in as little as one hour.

“These advances in the diagnosis of PCP have great potential for the development of highly sensitive point-of-care devices using direct patient samples and applicable in a wide variety of settings,” says the CIBERESP group leader. Enrique J. Calderón from the Virgen del Rocío University Hospital in Seville.

The researchers also emphasize that these techniques are very selective and can discriminate patients with other respiratory diseases derived from other microorganisms, thus allowing a more reliable diagnosis of infectious diseases.

Articles of reference:

Calvo-Lozano, O., Aviñó, A., Friaza, V., Medina-Escuela, A., S Huertas, C., Calderón, E. J., Eritja, E., Lechuga, L. M. (2020). Fast and accurate pneumocystis pneumonia diagnosis in human samples using a label-free plasmonic biosensor. Nanomaterials, 10(6), 1246. https://doi.org/10.3390/nano10061246

Pla, L., Santiago-Felipe, S., Aviñó, A., Eritja, R., Ruiz-Gaitán, A., Pemán, J., Friaza, V., Calderón, E.J. Martínez-Máñez, R., Aznar E. (2020). Triplex hybridization-based nanosystem for the rapid screening of Pneumocystis pneumonia in clinical samples. Journal of Fungi, 6(4), 292. https://doi.org/10.3390/jof6040292

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Non-invasive glucose sensing in tears

Currently numerous medical diagnoses or follow-ups of many diseases are carried out by conventional methods such as clinical tests in laboratories and hospitals, being these invasive, slow and expensive.

Thanks to advances in technology, Point-of-Care (PoC) devices allow testing and monitoring of a multitude of biomedical markers or parameters in order to: (i) reduce costs, save time and reduce the complexity of the analysis; (ii) allow analysis in medical centers, primary care centers or even at home and (iii) real-time results allow to accelerate the decision-making on a patient. Thus, PoC devices respond to a demand from medical doctors as is the efficient health service thanks to the rapid availability of the laboratory analysis results.

In this context, a team of scientists from Barcelona have collaboratively developed a non-enzymatic sensor for glucose sensing in a non-invasive manner in tears. The work, cover of the magazine Applied Materials Today, demonstrates the proof of concept of the functionality of this electrochemical sensor.

Ana Moya, researcher of the CIBER-BBN and member of the research group of the Institute of Microelectronics of Barcelona CSIC, responsible for the sensors manufacture explains how these devices are fabricated by the innovative technology of Printed Electronics. Specifically, electrochemical glucose sensors have been manufactured by printing microelectrodes using Inkjet Printing Technology (IJP) on a flexible substrate of polyethylene terephthalate (PET) with silver and gold inks. The IJP dispenses small drops of the material to be printed under a graphic environment. This direct writing approach without the need of masks drastically reduces the total manufacturing time and cost of the sensors, and facilitates iterative design changes during sensor development.

Gemma Gabriel, Scientific Coordinator of  NANBIOSIS U8. Micro–Nano Technology Unit and researcher of the CIBER-BBN in the Institute of Microelectronics of Barcelona CSIC, explains how the IJP is a promising and low-cost alternative to conventional microelectronic manufacturing technology, which will allow the creation of a multitude of highly specific sensor platforms and sensitive with analytical application in the medical area. In line with the research group, the advance in novel functional materials with these technologies is of paramount importance for the development of new generations of disposable sensor platforms to solve a wide range of applications in the medical field.

Agostino Romeo, member of the Smart nano-bio-devices Group at the Institut de Bioingenieria de Catalunya (IBEC) led by Samuel Sánchez, highlights how the use of copper oxide microparticles (CuO) has allowed the successful modification of the electrodes, leading to a sensitive, stable and cost-effective platform for the non-enzymatic detection of glucose. The selectivity, reproducibility and life time provided by this functionalization with CuO has shown that these sensors are reliable tools to perform a personalized diagnosis of the health of an individual.

The good sensitivity and selectivity of the electrochemical sensor presented here has made it particularly suitable for the non-invasive sensing of glucose in tears. This has been demonstrated in this study in which the glucose level in human samples has been measured and correlated with commercial devices.

All this allows us to foresee that the use of this type of sensors for the diagnosis of eye diseases such as diabetes, where it is possible to achieve a painless and non-invasive monitoring, has a great opportunity in a disease as widespread in the world as it is this one. Thus, versatility, short manufacturing time and low cost makes IJP a valuable technology alternative to traditional sensor manufacturing techniques. Thus, the technology here presented can be adapted for the detection of many other substances of interest in other fluids such as saliva or urine.

 

Article of Reference:

Romeo A, Moya A, Leung TS, Gabriel G, Villa R, Sánchez S.  “Inkjet printed flexible non-enzymatic glucose sensor for tear fluid analysis“. Applied Materials Today 10 (2018) 133-141

(DOI)

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