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RESEARCH





MILESTONES

Kick-off:       15 April 2021
End date:    15 April 2024



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   Development of NFC interface sensors for the measurement of biomarkers in blood
E-crome: biosensori su carta wireless per la telemedicina in oncologia e la misura di emocromo ed elettroliti

Valore totale del progetto: 146.020,05 € di cui 146.020,05 € a titolo di sostegno finanziario ricevuto dalla Regione Lazio.

ORIGINE DEI FONDI: FESR Fondo Europeo di Sviluppo Regionale - Programma Operativo regionale del Lazio - Programmazione 2014-2020. Avviso Pubblico: "Progetti di Gruppi di Ricerca 2020".
 





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 lazioinnova
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Progetto realizzato con il contributo di:
Regione Lazio, Lazio Innova.

POR FESR Lazio 2014-2020.
Avviso pubblico "Progetti di Gruppi di Ricerca 2020".

TEAM

Prof.ssa Fabiana ARDUINI
 Prof.ssa Cecilia OCCHIUZZI
Dott.ssa Viviana SCOGNAMIGLIO
Dott.ssa Mattea C. CASTROVILLI
Dott. Armando ORLANDI
Prof. Pierpaolo LORETI

COLLABORATIONS





 
Background

English

The vast majority of oral anticancer treatments, administered at home, and intravenous infusions in medical oncology units, can lead to a limitation of physiological marrow, liver, and renal functions. Therefore, periodic determination of the blood count (hemoglobin, platelet count, and leukocyte formula) and plasma electrolytes (potassium, sodium, calcium, and magnesium) is mandatory for proper monitoring of drug toxicity and to identify the most appropriate dosage for each individual patient.
In recent years, the introduction of oral targeted molecular drugs in the treatment of hormone-sensitive metastatic breast carcinoma, such as cyclin-dependent kinase 4/6 inhibitors (CDK 4/6i), proteins that modulate the cell division cycle, have revolutionized the treatment of one of the most common oncological diseases. With the introduction of these drugs and a significant improvement in patient survival, there has been a reduction in hospitalization, but also the simultaneous need for careful monitoring of blood dyscrasia and electrolytes, especially in the first 4-6 months of treatment, in order to monitor the specific toxicity of these drugs and identify the correct dosage.
CDK 4/6 inhibitors (ribociclib, palbociclib, and abemaciclib) not only exhibit significant anticancer activity but also specifically inhibit marrow precursors causing neutropenia and cardiotoxicity (exclusively associated with ribociclib) with an increase in the QT interval of the electrocardiogram which can lead to alterations, even anecdotally fatal, in cardiac rhythm. This specific spectrum of toxicity necessitates monitoring of the blood count, leukocyte formula, and plasma electrolytes, whose homeostasis is essential for proper myocardial contraction.

Italiano

La quasi totalità dei trattamenti antineoplastici orali, somministrati a domicilio, ed endovenosi, infusi nelle unità assistenziali di oncologia medica, possono determinare una limitazione delle fisiologiche funzionalità midollare, epatica e renale. A fronte di ciò la determinazione periodica dell’emocromo (emoglobina, conta piastrinica e formula leucocitaria) e degli elettroliti plasmatici (potassio, sodio, calcio, e magnesio) risulta essere mandatoria al fine di un corretto monitoraggio della tossicità dei farmaci e di individuarne la più adatta posologia per ogni singolo paziente.
Negli ultimi anni l’introduzione di farmaci orali a bersaglio molecolare nel trattamento del carcinoma della mammella metastatico ormono-sensibile, come gli inibitori delle cicline chinasidipendenti 4/6 (CDK 4/6i) proteine modulatrici del ciclo di divisione cellulare, hanno rivoluzionato il trattamento di una delle patologie oncologiche più frequenti. A fronte dell’introduzione di tali farmaci con un significativo miglioramento della sopravvivenza delle pazienti, si è assistito ad una ridotta ospedalizzazione, ma alla contestuale necessità di un attento monitoraggio della crasi ematica e degli elettroliti, principalmente nei primi 4-6 mesi di trattamento al fine di monitorare la tossicità specifica di questi farmaci ed individuarne il più corretto dosaggio.
I CDK 4/6i (ribociclib, palbociclib e abemaciclib) presentano, oltre ad una significativa attività antineoplastica, una specifica inibizione dei precursori midollari causando neutropenia e tossicità cardiologica (legata esclusivamente al ribociclib) con incremento del tratto QT dell’elettrocardiogramma che può determinare alterazioni, anche aneddoticamente fatali, del ritmo cardiaco. Questo spettro specifico di tossicità rende necessario il monitoraggio dell’emocromo, della formula leucocitaria e degli elettroliti plasmatici, la cui omeostasi è essenziale per la corretta contrazione miocardica.


Goals (Obbiettivi)

English

Development of

  • Paper-based biosensor platform for blood count and electrolytes.
  • NFC potentiostat.
  • Digital Health App and Cloud.
  • Secure data sharing/transmission system.
Benefits:
  • Improved quality of life.
  • Time savings.
  • Cost-effectiveness.
  • Quality of service.

Italiano

Sviluppo di:

  • Piattaforma biosensoristica su carta per emocromo ed elettroliti.
  • Potenziostato NFC.
  • App e Cloud per Sanità Digitale.
  • Sistema di condivisione/trasmissione sicura dei dati.
Benefici:
  • Qualità della vita.
  • Risparmio di tempo.
  • Economicità.
  • Qualità del servizio.


FACILITIES

 
The NFC measurement station HF Voyantic TagFormance

C66 Mobile Computer (Android 11)





DISSEMINATION

5 Luglio 2021
Kick-off Meeting


12 Settembre 2022
Keynote - Conferenza IEEE RFID TA

Prof.ssa F. Arduini
arduini
 Design of novel paper-based devices for smart analysis
In the last decade, electrochemical paper-based (bio)sensors have garnered much attention in the sensing field thanks to their cost-effectiveness, easiness to use, and miniaturization. Besides these characteristics in common with the other electrochemical (bio)sensors, the features of paper, such as foldability and porosity, have opened new unprecedented electrochemical (bio)sensor configurations allowing for reagent-free measurements, origami-like set-up, and the absence of sample treatment. Furthermore, paper-based electrochemical devices have overcome the limitation of other electrochemical sensors, being able to detect the target analytes not only in solution but also in aerosol phase and surface without any additional instrument, matching one of the top 10 emerging technologies of 2021, namely diagnosing diseases with a puff of breath. In addition, after the measure, the device can be burned, reducing waste management with a relevant decrease in analysis costs in the case of biological fluids. In this keynote, I will report how we have exploited the features of paper to design smart biosensors able to treat the sample, contain any reagent needed for the measurement, on-site synthesize nanomaterials, and make the measurement delivering novel paper-based devices.
2 Ottobre 2023
Workshop - Villa Celimontana, Roma

Prof.ssa Occhiuzzi
workshop_ecrome


 E-CROME Workshop

The workshop is dedicated to the presentation of the research activity carried out within the E-CROME project: Development of biosensors with wireless RFID-NFC interface for telemedicine, in the context of home care for oncological and terminal patients, in line with the regional ecosystem of innovation (Digital Health) and the theatics proper to Life Sciences (biosensors, telemedicine) and Security (Cyber security and privacy) funded by POR FESR Lazio 2014 - 2020, Public Notice "Projects of Research Groups 2020", subject to the findings of the preliminary investigation carried out by Lazio Innova S.p.A.
PUBLICATIONS
Journals



UHF RFID and NFC Point-of-Care – Architecture, Security, and Implementation
G. M. Bianco, E. Raso, L. Fiore, V. Mazzaracchio, L. Bracciale, F. Arduini, P. Loreti, G. Marrocco, and C. Occhiuzzi, IEEE Journal of Radio Frequency Identification (2023)
Points-of-care (PoCs) augment healthcare systems by performing care whenever needed and are becoming increasingly crucial for the well-being of the worldwide population. Personalized medicine, chronic illness management, and cost reduction can be achieved thanks to the widespread adoption of PoCs. Significant incentives for PoCs deployment are nowadays given by wearable devices and, in particular, by RFID (RadioFrequency IDentification) and NFC (Near Field Communications), which are rising among the technological cornerstones of the healthcare internet of things (H-IoT). To fully exploit recent technological advancements, this paper proposes a system architecture for RFID- and NFC-based PoCs. The architecture comprises in a unitary framework both interfaces to benefit from their complementary features, and gathered data are shared with medical experts through secure and user-friendly interfaces that implement the Fast Health Interoperability Resource (FHIR) emerging healthcare standard. The selection of the optimal UHF and NFC components is discussed concerning the employable sensing techniques. The secure transmission of sensitive medical data is addressed by developing a user-friendly ”PoC App” that is the first web app exploiting attribute-based encryption (ABE). An application example of the system for monitoring the pH and cortisol levels in sweat is implemented and preliminarily tested by a healthy volunteer.



Microfluidic paper-based wearable electrochemical biosensor for reliable cortisol detection in sweat

L. Fiore, V. Mazzaracchio, A. Serani, G. Fabiani, L. Fabiani, G. Volpe, D. Moscone, G. M. Bianco, C. Occhiuzzi, G. Marrocco, F. Arduini, Sensors and Actuators B: Chemical (2023)
Herein, we report the first paper-based microfluidic device encompassing the filter paper to manage the flow and to load the reagents for a reagent-free competitive magnetic-bead-based immunosensor for cortisol analysis in sweat. The paper-based microfluidic pattern was made using wax printing and laser-cutter techniques, for the delivery of capillary-driven microfluidics. The presence of magnetic beads functionalized with monoclonal antibodies for the recognition of the cortisol in the reaction zone allows for the specific measurement of the target analyte. The competitive reaction between the target cortisol and the labeled cortisol with acetylcholinesterase enzyme gives a response inversely proportional to the target cortisol in the range of 10 and 140 ng/mL, by simply folding the pad loaded with the enzymatic substrate. The paper-based microfluidic device was successively combined with a Near-Field Communication wireless module to develop a flexible integrated wearable analytical tool for cortisol detection in sweat. The paper-based integrated device was successfully applied to determine the level of cortisol in sweat in one volunteer during cycling activities at two different times, demonstrating the reliability of this sustainable paper-based device.



Privacy-Aware Architectures for NFC and RFID Sensors in Healthcare Applications

E. Raso, G. M. Bianco, L. Bracciale, G. Marrocco, C. Occhiuzzi, and P. Loreti, Sensors MDPI (2022)


World population and life expectancy have increased steadily in recent years, raising issues regarding access to medical treatments and related expenses. Through last-generation medical sensors, NFC (Near Field Communication) and radio frequency identification (RFID) technologies can enable healthcare internet of things (H-IoT) systems to improve the quality of care while reducing costs. Moreover, the adoption of point-of-care (PoC) testing, performed whenever care is needed to return prompt feedback to the patient, can generate great synergy with NFC/RFID H-IoT systems. However, medical data are extremely sensitive and require careful management and storage to protect patients from malicious actors, so secure system architectures must be conceived for real scenarios. Existing studies do not analyze the security of raw data from the  radiofrequency link to cloud-based sharing. Therefore, two novel cloud-based system architectures for data collected from NFC/RFID medical sensors are proposed in this paper. Privacy during data collection is ensured using a set of classical countermeasures selected based on the scientific literature. Then, data can be shared with the medical team using one of two architectures: in the first one, the medical system manages all data accesses, whereas in the second one, the patient defines the access policies. Comprehensive analysis of the H-IoT system can be useful for fostering research on the security of wearable wireless sensors. Moreover, the proposed architectures can be implemented for deploying and testing NFC/RFID-based healthcare applications, such as, for instance, domestic PoCs.
Electrochemical paper-based devices: When the simple replacement of the support to print ecodesigned electrodes radically improves the features of the electrochemical devices

F. Arduini, Current Opinion in Electrochemistry (2022): 101090.
Paper-based electrochemical (bio)sensors have emerged as highly attractive analytical devices for their superior sustainable features, such as avoiding the use of polyester as support and the reduction of waste, being incinerated after use. However, paper-based electrochemical (bio)sensors have recently demonstrated further advantages, including the simple combination with vertical microfluidics and their use as a reservoir to deliver smart electrochemical (bio)sensors able to i) contain the reagents, ii) preconcentrate the target analyte, and iii) synthesize the nanomaterials inside the paper network. Furthermore, these devices have demonstrated their ability to overcome the limitations of the other printed electrochemical sensors in the measurement of entirely liquid samples by detecting the target analyte in the aerosol phase or solid sample, without the additional sampling system. These achievements highlight their valuable and varied advantages in the sensing sector.
Nanomaterials and paper-based electrochemical devices: merging strategies for fostering sustainable detection of biomarkers
V. Caratelli, E. Di Meo, N. Colozza, L. Fabiani, L. Fiore, D. Moscone, & F. Arduini, (2022), Journal of Materials Chemistry B.
In the last few decades, nanomaterials have made great advances in the biosensor field, thanks to their ability to enhance several key issues of biosensing analytical tools, namely, sensitivity, selectivity, robustness, and reproducibility. The recent trend of sustainability has boosted the progress of novel and eco-designed electrochemical paper-based devices to detect easily the target analyte(s) with high sensitivity in complex matrices. The huge attention given by the scientific community and industrial sectors to paper-based devices is ascribed to the numerous advantages of these cost-effective analytical tools, including the absence of external equipment for solution flow, thanks to the capillary force of paper, the fabrication of reagent-free devices, because of the loading of reagents on the paper, and the easy multistep analyses by using the origami approach. Besides these features, herein we highlight the multifarious aspects of the nanomaterials such as (i) the significant enlargement of the electroactive surface area as well as the area available for the desired chemical interactions, (ii) the capability of anchoring biorecognition elements on the electrode surface on the paper matrix, (iii) the improvement of the conductivity of the cellulose matrix, (iv) the functionality of photoelectrochemical properties within the cellulose matrix, and (v) the improvement of electrochemical capabilities of conductive inks commonly used for electrode printing on the paper support, for the development of a new generation of paper-based electrochemical biosensors applied in the biomedical field. The state of the art over the last ten years has been analyzed highlighting the various functionalities that arise from the integration of nanomaterials with paper-based electrochemical biosensors for the detection of biomarkers.


Origami Paper-Based Electrochemical (Bio)Sensors: State of the Art and Perspective

N. Colozza, V. Caratelli, D. Moscone F. Arduini,  Biosensors 11.9 (2021):328.

In the last 10 years, paper-based electrochemical biosensors have gathered attention from the scientific community for their unique advantages and sustainability vision. The use of papers in the design the electrochemical biosensors confers to these analytical tools several interesting features such as the management of the solution flow without external equipment, the fabrication of reagent-free devices exploiting the porosity of the paper to store the reagents, and the unprecedented capability to detect the target analyte in gas phase without any sampling system. Furthermore, cost-effective fabrication using printing technologies, including wax and screen-printing, combined with the use of this eco-friendly substrate and the possibility of reducing waste management after measuring by the incineration of the sensor, designate these type of sensors as eco-designed analytical tools. Additionally, the foldability feature of the paper has been recently exploited to design and fabricate 3D multifarious biosensors, which are able to detect different target analytes by using enzymes, antibodies, DNA, molecularly imprinted polymers, and cells as biocomponents. Interestingly, the 3D structure has recently boosted the self-powered paper-based biosensors, opening new frontiers in origami devices. This review aims to give an overview of the current state origami paper-based biosensors, pointing out how the foldability of the paper allows for the development of sensitive, selective, and easy-to-use smart and sustainable analytical devices.
Conferences



Professor Occhiuzzi presenting the work in Japan.
 Four-Channel NFC System for Electrochemical Sensing of Fluids

G. M. Bianco, V. Mazzaracchio, L. Fiore, F. Arduini, G. Marrocco and C. Occhiuzzi, presented at IEEE SENSORS 2024, Oct. 20-23, Kobe, Japan, 2024

Electrochemical analysis systems are increasingly important for applications like Point-of-Care diagnostics and Lab-on-Package sensing. Herein, we propose a system composed of four passive NFC (Near Field Communication) microchips capable of performing open circuit potentiometry through interactions with commercial smartphones. The multi-chip NFC system can be used to quantify four chemical quantities within a unique liquid sample thanks to a microfluidic circuit which feeds four ad-hoc screen-printed electrodes. In this contribution, preliminary calibration on four analytes is reported. The four target quantities considered in this paper are sodium, potassium, calcium, and pH. The sensing matrix will be human blood and fluids derived from food spoilage Thanks to further implementation with microfluidic channels currently under development, the NFC chemical analyses can facilitate domestic monitoring of patients and rapid, on-site test of pieces of food to check food quality and prevent foodborne illnesses.



Deployment of a Multi-Chip NFC System with Microfluidic for Electrochemical Sensing

G. M. Bianco, V. Mazzaracchio, L. Fiore, F. Arduini, G. Marrocco, and C. Occhiuzzi,  2024 IEEE International Symposium on Antennas and Propagation and ITNC-USNC-URSI Radio Science Meeting (AP-S/URSI 2024)

Fast, on-site chemical sensing can be a powerful tool for many applications, ranging from point-of-care analyses to food quality checks. NFC (Near Field Communications) devices capable of chemical sensing have recently become available. However, they are still limited to sensing a single chemical species at a time, whereas usually, an array of species should be quantified during the same analysis. Multi-chip NFC devices are still unavailable for chemical sensing, and the use of microfluidics with delay lines is also necessary for the correct delivery of liquid samples. Accordingly, this contribution explores the layout design of the first multi-chip NFC system integrated with microfluidics for electrochemical sensing using multiple boards simultaneously. The most functional arrangement of the responders is experimentally selected based on their read areas, the quality of the NFC communication, and the microfluidic characteristics. Lastly, a four-channel microfluidic system is integrated with the best board placement and validated by quantification of sodium in standard solution.



Design and Manufacture of Flexible Epidermal NFC Device  for Electrochemical Sensing of Sweat

A. B. Barba, G. M. Bianco, L. Fiore, F. Arduini, G. Marrocco and C. Occhiuzzi,  2022 IEEE International  Conference on Flexible and Printable Sensors and Systems (FLEPS)

Flexible and epidermal sensing devices are becoming vital to enable precision medicine and telemonitoring systems. The NFC (Near Field Communication) protocol is also becoming increasingly important for this application since it is embedded in most smartphones that can be used as pervasive and lowcost readers. Furthermore, the responder can be passive and can harvest enough power to perform electromagnetic sensing. Finally, the NFC coils are robust to bending and to the human body’s presence. This contribution details the design of a new flexible device, including an electrochemical sensor communicating through the NFC protocol. A spiral NFC antenna is designed, and a manufactured prototype is experimentally tested to quantify the robustness to the inter-wearer variability and the bending. Lastly, the sensory data retrieval is validated by comparison with a portable potentiostat. The realized sensor can be comfortably worn and be easily read by smartphones independently from the wearer and from the point of application and could be used in future for estimating the user’s psycho-physical health by analyzing the body’s sweat.


Towards a Hybrid UHF RFID and NFC Platform for the Security of Medical Data from a Point of Care

G. M. Bianco, E. Raso, L. Fiore, A. Riente, A. B. Barba, C. Miozzi, L. Bracciale,  F. Arduini, P. Loreti, G. Marrocco and C. Occhiuzzi,  2022 IEEE International  Conference on RFID Technology and Applications (RFID-TA)
In recent years, body-worn RFID and NFC (near field communication) devices have become one of the principal technologies concurring to the rise of healthcare internet of thing (H-IoT) systems. Similarly, points of care (PoCs) moved increasingly closer to patients to reduce the costs while supporting precision medicine and improving chronic illness management, thanks to timely and frequent feedback from the patients themselves. A typical PoC involves medical sensing devices capable of sampling human health, personal equipment with communications and computing capabilities (smartphone or tablet) and a secure software environment for data transmission to medical centers. Hybrid platforms simultaneously employing NFC and ultra-high frequency (UHF) RFID could be successfully developed for the first sensing layer. An application example of the proposed hybrid system for the monitoring of acute myocardial infarction (AMI) survivors details how the combined use of NFC and UHF-RFID in the same PoC can support the multifaceted need of AMI survivors while protecting the sensitive data on the patient’s health.

An RFID Sensor with Microfluidic for Monitoring the pH of Sweat During Sport Activity

A. Riente, G. M. Bianco, L. Fiore,  F. Arduini, G. Marrocco and C. Occhiuzzi,  17th European Conference on Antennas and Propagation (EuCAP2023)
Among the multiple healthcare applications and systems exploiting sensing RFID boards, monitoring sweat's pH can be extremely useful for sportsmen and sportswomen. Furthermore, given the multiple known benefits that sports yield, measuring pH during physical activity can be integrated with points-of-care (PoCs) for patients who need working out. This contribution details the experimental testing of an RFID sensor for measuring sweats pH during sporting activity. The electromagnetic (EM) performances are quantified over multiple wearers, and new, low-cost microfluidics made of absorbent paper is manufactured, characterized, and tested so that the use of the tag during exercise is proven feasible.


AWARDS

arduini
 Third Classified, Best Paper Award at IEEE RFID-TA 2022

G. M. Bianco, E. Raso, L. Fiore, A. Riente, A. B. Barba, C. Miozzi, L. Bracciale,  F. Arduini, P. Loreti, G. Marrocco and C. Occhiuzzi, "Towards a Hybrid UHF RFID and NFC Platform for the Security of Medical Data from a Point of Care"