Publications

Infoscience

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Books

1. Sandro Carrara, Krzysztof Iniewski, (Eds), Handbook of Bioelectronics, Cambridge University Press, Cambridge, 2015 // 2. Sandro Carrara (Aut), Bio/CMOS Interfaces and Co-Design, Springer, New York, 2013 // 3. W.Burleson & S.Carrara (Eds), Security and Privacy for Implantable Medical Devices, Springer, NY, 2014 // 4. Sandro Carrara (Ed), Nano-Bio-Sensing, Springer, New York, 2011 // 5. Sandro Carrara (Aut), Che cosa è il tempo? (italian), Simonelli, Milan, 2011 // 6. Alexander Schmid, al. et S.Carrara (Eds), Nano-Net, Springer, Berlin, 2009 // 7. C.A. Nicolini, S. Carrara, et al. (Auts), Molecular Bioelectronics, World Scientific, Singapore, 1996

EPFL patents

S. Carrara, F. Stradolini, T. Kilic (2017), Fouling-resistant Pencil Graphite electrode, international Patent Application n° PCT/IB2017/053175 G. Köklü, S. Carrara, G. De Micheli (2013), A novel CMOS Image Sensor with Event/Change Detection and Reduced Data Redundancy. Provisional U.S. Patent Application No. 61/816,197 I. Taurino, M. Arnaud, F. Laszlo, G. De Micheli, S. Carrara, (2013) Close and Selective Integration of Carbon Nanomaterials by CVD onto working microelectrodes of multi sensing electrochemical biosensors, filed on September 13th 2013, European Patent Registration # EP 13184291.6

Recherche

Present research projects

H2020 project Cybercare: Integrated Sensing Architectures and Tools for Health Care
This research project addresses high-risk, high-reward research of integrated sensing and computing architectures, as well as of models, methods and tools for their design and operation. Such architectures provide the bridge between bio-systems and information processing systems. Breakthroughs in data acquisition, processing and decision making support will enable new smart-health applications. This project also aims at the development of wearable multi-sensing platform for ion-sensing. Sweat is used here as main sample fluid because it represents a promising substitute to blood thanks to the simple artificial reproducibility and to the large accessibility that does not require invasive or painful procedures.

SNF/Fondazione San Paolo project CoMofA
Every year, 30,000 people undergo anesthesia and remain awake, still feeling pain while not being able to move, due faulty drug administration. Proper anesthesia requires the achievement of a certain target plasma concentration of drugs, typically injected by Target Controlled Infusion (TCI) systems, with prediction errors in control models reaches 20-30% due to the patients' diversity. Therefore, continuous monitoring of anesthetic agents circulating in body fluids would contribute to better individualization of patients' management. We propose to create a system with a semi-closed-loop control for anesthesia delivery based on the anesthetics monitoring in human fluids.

CTI/project: Integrated ion-sensor platform for remote monitoring of water networks
The company Microsens, a company of the EPFL Scientific Park, has more than 20 years experience on devices for water quality monitoring. On the other hand, École Polytechnique Fédérale de Lausanne, EPFL is currently developing electrochemical sensors for monitoring ions. Therefore, EPFL and Microsens would like to merge the ideas and technologies for investigation of innovative nano-sensors for continuous monitoring of the water quality. Electrochemical sensors are chosen because they can be easily integrated with electronics to provide automated monitoring in the field, including wireless transmission thank to an approach that we have already successfully demonstrated for medical applications.

Past research projects

Breast cancer-on-a-chip with integrated sensors for drug screening
The goal of the present project is to design a breast-cancer-on-a-chip with integrated electrochemical sensors for circulating miRNA and exosome detection to test efficacy of chemotherapeutics. Herein, BC spheroids will be cultured 3D in PDMS based microfluidic bioreactor that is connected to multiple electrochemical sensors for on-line monitoring of biomarker secretion. The results obtained via EC sensors will be evaluated via additional methods such as qRT-PCR and ELISA and will provide the basis for future exosome and circulating miRNA detection from cell culture media since it will be the first study in literature. Overall, this project aims to open new approaches for chemotherapeutic screening and help prevention the global population suffering from breast cancer.

UE COST Action MemoCiS
The invention of the transfer resistor, or transistor as it is know today, is considered to be the greatest invention of the 20th century, as it forms the basis of all electronic systems. The next technological revolution will come through self-organizing and self-programming circuits and systems, which are similar to biological brains in that they can learn to perform tasks. This COST action is aimed at bringing together researchers of different backgrounds to work in unison so as to overcome multidisciplinary barriers in the area of memristors. The creation of the hardware basis for future self-organizing/self-programming systems will really open up a wide range of application areas and new industries, e.g. humanoid robots to look after the elderly, self-driven vehicles etc.

Pierre Fabre: Feasibility Study for Nicotine detection on skin sweat
The company PIERRE FABRE MEDICAMENT, IRPF is conducting a product development program regarding the detection of nicotine inside human perspiration. On the other hand, École Polytechnique Fédérale de Lausanne, EPFL is currently developing electrochemical sensors for monitoring biomarkers such as drugs, metabolites inside human perspiration. Therefore, EPFL and Pierre Fabre would like to merge the ideas and technologies for investigation of electrochemical sensor development for the detection of nicotine inside perspiration.

SNF project Reprogramming of Tie-2 Expressing Monocytes (TEM) in breast cancer
The key scientific purpose of this new project proposal is to understand the functional behavior of TEM in breast cancer in order to design optimal treatments able to reverse TEM into cells promoting protective anti-tumor immune responses. To this end, we will take advantage of our nanowire detection approach using multiplexed nanowire arrays sensing a panel of secretion markers reflecting TEM hemangiogenic, lymphangiogenic, immune suppressive, tumoricidal and anti-tumor activities. We plan also to use nanowire arrays to capture TEM landscape directly on the tumor tissue. This approach represents the first attempt to capture the tumor microenvironment leaving intact the tumor tissue for complementary characterization by confocal microscopy.

Food-Allergy-Chip: platform to investigate food allergy
Food allergy tests are done by Skin tests, including the prick test and the scratch test however, these tests are dangerous because of anaphylaxis by serum antibodies. Therefore, a safe, simple and rapid method for detecting allergic reaction is required for clinical use and in the food industry. A recent study on mice showed that common bacteria called Clostridia help prevent sensitization to food allergens in mice. While IL-22 is known to be a key signaling molecule to decrease the permeability of the intestinal lining to prevent allergens to enter your bloodstream. Therefore, the aim of this project is to study food allergy and the effect of gut microbiome against food allergens by a Food-Allergy-Chip where electrochemical biosensors will monitor food-allergy biomarkers, including interleukin-22 (IL-22).

UE ITN Project on Prostate Cancer
The Marie Curie Initial Training Network PROSENSE aims at training a new generation of young scientists in the interdisciplinary techniques and methods required to meet the major challenges in the development of diagnostic tools for prostate cancer. A full program of cross-disciplinary and cross-sectorial students exchange, training and events will enable PROSENSE to promote interaction, knowledge exchange and collaboration in the multidisciplinary field of biosensor design with the aim of developing improved devices for prostate cancer diagnosis, prognosis and treatments.

Pierre Fabre: Feasibility Study for Drugs in Schizophrenia
The company PIERRE FABRE MEDICAMENT, IRPF is conducting a development program regarding new product with also organic small molecule with property as anti-cancer agent, exclusive property of PIERRE FABRE MEDICAMENT. On the other hand, the EPLF is currently developing devices that also integrate electrochemical sensors for the continuous monitoring of exogenous substances such as drugs, including compounds for schizophrenia treatment. Therefore, both parties joined the efforts to investigate the possibility to apply the technology under development in EPFL to the PIERRE FABRE’ products.

NTF IronIC
The project aims to develop a new system for continuous monitoring of critical patients in intensive care units (ICU). Patients in intensive care units are typically under the risk of fatal due to Systemic Inflammatory Response Syndrome (SIRS), a generic systemic response. If not treated within the first 48 h in ICU, it usually evolves to Multiple Organ Failure Syndrome (MOFS) and, then, in the death of the patient. However, commonly monitored physiological parameters do not allow early diagnosis and prediction of deterioration toward multiple organ failure. Therefore, this project aims to development of definitely new diagnostic tools capable of continuous monitoring of some critical metabolites in interstitial fluid (ISF) might significantly reduce mortality of these patients.

EPFL CNU project BactoChip
The intestinal epithelium provides a selective barrier that protects the human organism from the invasion of pathogens and other undesired external factors but, at the same time, allows an efficient uptake of nutrients from the diet. In order to let macronutrients present in foods to be transferred across the intestinal barrier, the ingested macromolecules need to be broken into their building blocks. Recent research has demonstrated that commensal bacteria participate to a significant extend to the metabolism of nutrients by producing digestive enzymes as well as by influencing the intestinal transport of nutrients. We aim now to develop a new Lab-on-a-Chip platform (the BactoChip) that integrates a biofilm of a commensal E. coli strain to mimic the distal part of the intestine that is highly populated by bacteria.


System for Drug Monitoring in Personalized Therapy (Prolongation)
The aim of this project is to address the novel issues that emerged during the first stage of the research. To this end, we target now the development of new multi-panel array including linear and non-linear approaches to improve sensors specificity at system level, the design and implementation of an external control unit to improve the efficiency of the Remote Powering System for the final tests in vivo with Freely Moving Mice; the monitor active drugs in vivo, and the design, cloning, and expressing mutants of some probe P450 isoforms to improve the enzymes-substrates kinetics.

Tie-2-expressing monocytes - Appealing targets in breast cancer angiogenesis
This project proposes a new detection methodology based on memristive-effect registered on silicon nanowire to detect a new class of cancer markers. The nano-wires are fabricated by an innovative lithographic technique that allows precise and selective etching at the nanoscale. The wires are obtained in three main steps. Initially, a photoresist line defines the wire position. In a second step, silicon deep reactive ion etching is performed to obtain a scalloped trench. In the final step, the trench is reduced to a suspended nanowire after wet oxidation. The obtained wires present are functionalized with antibodies in order to sense the cancer markers on dried samples.

IronIC/Nanotera Project
The aim of this project is to study an innovative, multi-metabolites, highly integrated, fully implantable, and real-time monitoring system for human metabolism. The monitored metabolic molecules are not limited to lactate, glucose, ATP, Arachidonic Acid, Bilirubin, and others. To pursue this aim, the project is developing an innovative technology by integrating SW/HW/RF/micro/nano/bio systems in three devices: (i) a fully implantable sensors array for data acquisition; (ii) a wearable patch for remote powering and data acquisition; (iii) a Bluetooth connection to a smartphone.

Sinergia Project on Drug Monitoring
A fully mature biochip system capable of continuous monitoring drugs and biomarkers in blood, or in sub-cutaneous districts is under development and it constitutes a major breakthrough in molecular medicine for personalizing therapy of complex diseases. The aim of the present project is to undertake a multidisciplinary approach to substantially advance the state-of-the-art of implantable devices. The project requires a strong convergence between micro-nano-bio-medical technologies with the motivation to provide a new tool for the direct monitoring of the patient's drug metabolism in personalized pharmacological treatments.

NutriChip/Nanotera Project
The NutriChip project will combine biological sciences, nanotechnology, micro-technology and system integration aspects applied by a multidisciplinary team to develop an efficient analytical tool to gain holistic insight into the contribution of dairy products to human nutrition and health. Cells surface receptors called TLR2/4 were recently found to be down regulated in overweight and obese patients, and TLR4 is a receptor for dietary fat. So, a hardware interface is under development in order to detect TLR receptors in CaCo2 cells by combining a CMOS low-noise imager and required super-resolution algorithms.

iNeedle/Nanotera Project
The project aims at the realization of an acupuncture i-needle for measuring Temperature, pH, and rotational velocity in animal tissues. A feasibility study is also conducted in order to evaluate the possibility to integrate molecular sensors in the i-needle I order to measure metabolites released in the extracellular matrix by the acupuncture treatment. Therefore, this project aims at providing a new tool to address the currently lacking systematic and scientific evidence of the physical and molecular mechanisms acting behind the acupuncture therapy.

To see more details on the research, please, link to the page:
https://icwww.epfl.ch/~scarrara/Research.htm

National and International Collaborations

Running
Pantelis Georgiou(Imperial Collage, London)
Jun Ohta (Nara Institue of Science and Technology)
Marie-Agnès Doucey (Ludwig Institute for Cancer Research)
Christine Nardini (Karolinska Institute, Sweden)
Danilo Demarchi (Politecnico di Torino)
Thierry Buclin (CHUV, University of Lausanne)
Catherine Dehollain (EPFL, Lausanne)

Former
Ali Khademhosseini (Harvard, Boston)
Ralph Etienne-Cummings (Johns Hopkins University, Baltimore)
Anthony Guiseppi-Elie (Clemson University/South Carolina)
Mohamad Sawan (École Polytechnique de Montréal, Canada)
Elisabetta Chicca (Universty of Bielefeld/DE)
Ursula von Mandach (Zurich University)
Linda Thöny-Mayer (EMPA/San Gallen)
Pedro Estrela (University of Bath/UK)
Qiuting Huang (ETHZ, Zurich)
Fabio Grassi (IRB/Bellinzona)
Paolo Silacci (ALP/Posieux)
Guy Vergères (ALP/Bern)
Pascal Colpo (EU JRC/Ispra)
Yusuf Leblebici (EPFL, Lausanne)
Martin Gijs (EPFL, Lausanne)
Philippe Renaud (EPFL, Lausanne)
Giacomo Indiveri (University of Zurich, ETHZ)