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Self-Healthcare for breast cancer detection using an INtegrated paper-based Electrochemical device

Periodic Reporting for period 1 - SHINE (Self-Healthcare for breast cancer detection using an INtegrated paper-based Electrochemical device)

Berichtszeitraum: 2019-01-07 bis 2021-01-06

Among women, breast cancer is the largest killer in the world. Detecting breast cancer at a curable stage will improve the chance of survival. Although mammography and alternative techniques can diagnose breast cancer, these tests require specialized laboratories and skilled personnel, and suffer of many drawbacks ranging from limitation of mammography to over 40 to the extremely invasive (painful) tissue biopsies. Moreover, tremendous limitations are encountered in low-resource countries, where the maldistribution of cancer care centers, the scarcity of specialists and financial restrictions don't allow all the women to easily access breast cancer screening tests. The presence of circulating mutations opens to a cutting-edge opportunity in cancer diagnosis. Detection of mutations in blood, known as liquid biopsy, offers a revolutionary non-invasive procedure for cancer detection and therapies monitoring. The objective of this project is the development of a hand-held electrochemical microfluidic paper-based analytical device that will enable the rapid detection of breast cancer by the quantitative detection of circulating tumour DNA in whole blood (SHINE).The relevance of this proposal will be in the development of a sensitive, rapid, and cost-effective device that will be used in the personalized medicine by nonspecialists, going beyond the state of the art represented by methods that require skilled personnel, expensive equipment and complicate/time consuming work flow. SHINE will be the first point-of-care device for breast cancer detection that is not currently available. It will be available all over the world and in particular will be used in the developing countries that cannot afford costs of the current breast cancer screening. In addition, SHINE will be a starting point extensible to others cancer liquid biopsies, i.e. pancreatic cancer that is very difficult to detect at a curable stage so far.
The rising demand for user-friendly analytical devices high-lights the versatility and potential of paper-based tools as a pivotal forerunner for the development of (bio)sensors. Emerging technologies, such as liquid biopsy, have been coupled with electroanalytical platforms and corresponding technologies with easy fabrication routes. During the period covered by the report (three months), the two most common strategies for detection of nucleic acids have been utilized for DNA analysis. Signal ON and Signal OFF systems, i.e. signal increases in presence of the mutation (ON) and signal decreases in presence of the mutation (OFF), have been implemented towards the determination of a single strand DNA relative to a missense mutation in breast cancer, specifically H1047R (A3140G) missense mutation in exon 20 in breast cancer. The results have been achieved in collaboration with the Hospital Sant Joan de Déu of Barcelona, and according to literature, a DNA sequence related to a mutation in PIK3CA oncogene has been identified and the complementary probe has been designed.
This study has also allowed to produce a protocol, highlighting some key factors that should be considered prior to the fabrication and use of the paper-based strip applied for DNA analysis.
Beyond the state of the art, the detection of circulating mutation has been evaluated with the two above cited approaches, highlighting the Signal OFF platform as the optimal compromise of manufacturing and ease of use.

The objective related to the reported period was achieved following periodically seminars and/or workshops on the resolution of specific tasks related to the project acquiring additional scientific and complementary skills.

As part of the dissemination and communication activities, among the various deliverables, during the three-month period of work, two main activities have been produced to spread the SHINE project. In particular, a seminar for members of ICN2 has been held and the project has been also explained within a communication science contest that was dedicated to non-specialized audience. In particular, the Barcelona Science Slam has been organized by the Marie Curie Alumni Association encouraging PhD students and postdoctoral researchers to participate, providing an exciting opportunity to learn about a broad range of scientific fields and to share their research closer to society. In addition to this, the contest offered the possibility to attend a two-day workshop for enhancing the communication skills, trained by experts in communication at the Centre for Genomic Regulation.
The progress beyond the state of the art, relatively to the reported period, can be described by the following points:

- Identification of missense mutation in breast cancer for diagnosis and evaluation of the therapeutic process: this sequence can be used as the starting point to develop novel system to enhance the self-healthcare in the field of cancer treatment;
- Analytical characterization and comparison between two approaches of nucleic acid sensing, i.e. Signal ON and Signal OFF: future researcher will be able to decide which is the optimal platform for detecting nucleic acids, even for other application not only in the clinical field but also in the environmental and agri-food fields.
- Protocol for developing paper-based electrochemical DNA tools: as the exploitable result is the capacity in designing a paper-based strip including all the steps and modification.

The potential impact of SHINE could encompass social, economic and environmental aspects as well, following a common sustainability vision.

1) Social aspect. The use of paper-based platforms offers the possibility to furnish miniaturised, cost-effective, and environmental friendly devices. These devices allow to perform measurements by un-skilled personnel without requiring laboratory set-up, delivering useful devices especially in those resource-limited areas.

2) Economic aspect. It has been reported that merely by replacing plastic by filter paper in strips fabrication, the cost is reduced of more than 50% at laboratory scale manufacturing process. Just considering the glucose test strips used every year by diabetic patient (750 millions, http://www.glucometrix.de/eng/markt.php) as case of study for this discussion, the replacing of plastic-based strips will have a tremendous economic impact on the strips manufacturing process, delivering more cost-effective strips even in the field of cancer care.

3) Environmental aspect. Regarding the analytical methodologies, the 11th of the 12 Principles of Green Chemistry established by Anastas and Warner is focused on the development of real-time analysis to accomplish the environmentally friendly approach. In addition, a sustainable analytical method should minimise the production of hazardous waste to reduce the environmental impact even because the strips are fabricated from non toxic materials and they can be easily incinerated after the measurement reducing the waste.
Scheme of SHINE and electrochemical response with the ON e OFF approaches for determining mutations