Design and Realization of Biomedical Applications

Activity Abstract

MiNES Group is active in several branches of Biomedical Engineering. The trait d’union is the design of integrated low power electronic interfaces, in combination with the realization of innovative biosensors.

The most important activities are:

• Low Power Smart Electronic Systems for Drug Delivery Implantable Devices
• Design and implementation of low-power wireless interfaces for biosignals and biodevices
• Realisation of electronic systems for cell cultures and organs-on-chips
• Study of ElectroChemiLuminescent sensors for biomolecules

Low Power Smart Electronic Systems for Drug Delivery Implantable Devices.

Implantable devices are one of the most interesting solution for future biomedical monitoring and treatment technologies.

In this area MiNES researchers are cooperating with the team of Alessandro Grattoni and Mauro Ferrari at the Houston Methodist Hospital,  working on the design of Smart Electronic Systems with Low Power solutions, bridging the request of long term implants and an efficient exchange of data with the devices.

A very important achievment has been reached with the publication in Nature Communications “G. Bruno, N. Di Trani, R. L. Hood, E. Zabre, C. S. Filgueira, G. Canavese, P. Jain, Z. Smith, D. Demarchi, S. Hosali, A. Pimpinelli, M. Ferrari, and A. Grattoni, Unexpected behaviors in molecular transport through size-controlled nanochannels down to the ultra-nanoscale, Nature Communications, vol. 9, no. 1, p. 1682, Apr. 2018“.

As product of this activity, several other papers were published in important International Journals as:

• G. Bruno, G. Canavese, X. Liu, C. S. Filgueira, A. Sacco, D. Demarchi, M. Ferrari, and A. Grattoni, “The active modulation of drug release by an ionic field effect transistor for an ultra-low power implantable nanofluidic system” Nanoscale, vol. 8, no. 44, pp. 18718–18725, Nov. 2016.
• M. Farina, C. Y. X. Chua, A. Ballerini, U. Thekkedath, G. Torchio, J. F. Alexander, J. R. Rhudy, D. Fraga, R. R. Pathak, M. Villanueva, C. S. Shin, J. A. Niles, R. Sesana, D. Demarchi, A. G. Sikora, G. S. Acharya, A. O. Gaber, J. E. Nichols, and A. Grattoni, “Transcutaneously refillable, 3D-printed biopolymeric encapsulation system for the transplantation of endocrine cells” Biomaterials, vol. 177, pp. 125–138, 2018.
• M. Farina, A. Ballerini, D. W. Fraga, E. Nicolov, M. Hogan, D. Demarchi, F. Scaglione, O. M. Sabek, P. Horner, U. Thekkedath, O. A. Gaber, and A. Grattoni, “3D Printed Vascularized Device for Subcutaneous Transplantation of Human Islets”, Biotechnol J, vol. 11, no. 9, p. 1700169, Jul. 2017.
• M. Farina, A. Ballerini, G. Torchio, G. Rizzo, D. Demarchi, U. Thekkedath, and A. Grattoni, “Remote magnetic switch off microgate for nanofluidic drug delivery implants”, Biomed. Microdevices, vol. 19, no. 2, p. 42, Jun. 2017.

 

Design and implementation of low-power wireless interfaces for biosignals and biodevices

This Activity it is directly related to the realization of Ultra-Low-Power Wireless Devices, the application of Bio-Inspired Electronics and the experience in the design of ReadOut Circuits for Robotics. These different Group knowledges are applied for the realization of innovative biomedical devices.

The best example of the MiNES Activities in this field is the work presented in the paper “S. Sapienza, M. Crepaldi, P. Motto Ros, A. Bonanno, and D. Demarchi, On Integration and Validation of a Very Low Complexity ATC UWB System for Muscle Force Transmission, IEEE Trans. Biomed. Circuits Syst., pp. 497-506, May 2015” where it is presented the application of the thresholding of Surface ElectroMyoGraphic (sEMG) signals, i.e., Average Threshold Crossing (ATC) technique, for reducing the amount of data to be processed enabling circuit complexity reduction and low power consumption (see the picture, extracted from this paper, courtesy of IEEE).

The work investigated the lowest level of complexity reachable by an ATC system through measurements and by in-vivo experiments, with an embedded prototype for wireless force transmission, based on asynchronous Impulse-Radio Ultra Wide Band (IR-UWB), the feasibility of the system was proven. The prototype is composed by the acquisition unit, a wearable PCB 23×34 mm2, which includes a full custom IC integrating a UWB transmitter and the receiver.

The system is completely asynchronous, it acquires a differential sEMG signal, generates the ATC events and triggers a 3.3 GHz IR-UWB transmission.

Other works related to the detection, elaboration and trasmission of biosignals, done by MiNES Group, are described in the papers:

• A. Gabrielli, S. Bastianini, M. Crepaldi, G. D’Amen, D. Demarchi, I. Lax, P. Motto Ros, and G. Zoccoli, “Low power wireless ultra-wide band transmission of bio-signals,” Journal of Instrumentation, vol. 9, no. 1, p. C12002, Dec. 2014
• A. Shahshahani, M. Shahshahani, P. Motto Ros, A. Bonanno, M. Crepaldi, M. Martina, D. Demarchi, and G. MASERA, “An All-Digital Spike-based Ultra-Low-Power IR-UWB Dynamic Average Threshold Crossing Scheme for Muscle Force Wireless Transmission,” presented at the DATE, 2014, pp. 1–6
• P. Motto Ros, M. Paleari, N. Celadon, A. Sanginario, A. Bonanno, M. Crepaldi, P. Ariano, and D. Demarchi, “A wireless address-event representation system for ATC-based multi-channel force wireless transmission,” Advances in Sensors and Interfaces (IWASI), 2013 5th IEEE International Workshop on, pp. 51–56, 2013
• M. Crepaldi, M. Paleari, A. Bonanno, A. Sanginario, P. Ariano, D. H. Tran, and D. Demarchi, “A quasi-digital radio system for muscle force transmission based on event-driven IR-UWB,” presented at the Biomedical Circuits and Systems Conference (BioCAS), 2012 IEEE, 2012, pp. 116–119

Activities related to the use of UWB technique for biomedical applications were focused to the design and realization of in-vivo dosimeters and radiation measurements, as reported in the following papers:

• E. G. Villani, M. Crepaldi, D. Demarchi, A. Gabrielli, A. Khan, E. Pikhay, Y. Roizin, A. Rosenfeld, and Z. Zhang, “A monolithic 180 nm CMOS dosimeter for wireless In Vivo Dosimetry,” Radiation Measurements, vol. 84, pp. 55–64, Jan. 2016
• A. Gabrielli, M. Crepaldi, D. Demarchi, P. M. Ros, and G. Villani, “Wireless ultra-wide-band transmission prototype ASICs for low-power space and radiation applications,” Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, vol. 765, pp. 219–222, Nov. 2014
• F. Fuschino, A. Gabrielli, G. Baldazzi, R. Campana, S. Valentinetti, M. Crepaldi, D. Demarchi, and G. Villani, “A wireless transmission low-power radiation sensor for in vivo dosimetry,” J Inst, vol. 9, no. 2, pp. C02016–C02016, Feb. 2014
• S. Bastianini, M. Crepaldi, D. Demarchi, A. Gabrielli, M. Lolli, A. Margotti, G. Villani, Z. Zhang, and G. Zoccoli, “A 0.18μm CMOS low-power radiation sensor for asynchronous event-driven UWB wireless transmission,” Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, vol. 730, pp. 105–110, Dec. 2013;
• E. G. Villani, A. Gabrielli, D. Demarchi, and M. Weber, “Novel approaches to radiation detection and readout using the latch up effect,” Nuclear Instruments and Methods in Physics Research Section A, vol. 604, no. 1, pp. 416–419, Jun. 2009

 

Realization of electronic systems for cell cultures and organs-on-chips

In cell cultures the efficiency of sensors is one of the important features nowadays requested for obtaining integrated and efficient systems. MiNES Group is active in the realization of electronic interfaces for biosensors useful in cell culturing in general, and in organs-on-chip ion particular, thank you to a cooperation with the Khademhosseini Lab former in Boston, MA, now in UCLA, CA.

The best result obtained in the cooperation with Khademhosseini’s lab is the design and realisation of a soft-robot based on cardiac cells. To create life-like movements, living muscle actuator technologies have borrowed inspiration from biomimetic concepts in developing bioinspired robots. In this work, the development of a bioinspired soft robotics system, with integrated self-actuating cardiac muscles on a hierarchically structured scaffold with flexible gold microelectrodes has been implemented. Inspired by the movement of living organisms, a batoid-fish-shaped substrate was designed and reported, composed of two micropatterned hydrogel layers.

“S.-R. Shin, B. Migliori, B. Miccoli, Y. C. Li, P. Mostafalu, J. Seo, S. Mandla, A. Enrico, S. Antona, R. Sabarish, T. Zheng, L. Pirrami, K. Zhang, Y. S. Zhang, K. T. Wan, D. Demarchi, M. R. Dokmeci, and A. Khademhosseini, “Electrically Driven Microengineered Bioinspired Soft Robots,” Adv. Mater., vol. 30, no. 10, Jan. 2018“.

 

A significant paper is “Y. S. Zhang, F. Busignani, J. Ribas, J. Aleman, T. N. Rodrigues, S. A. M. Shaegh, S. Massa, C. B. Rossi, I. Taurino, S.-R. Shin, G. Calzone, G. M. Amaratunga, D. L. Chambers, S. Jabari, Y. Niu, V. Manoharan, M. R. Dokmeci, S. Carrara, D. Demarchi, and A. Khademhosseini, Google Glass-Directed Monitoring and Control of Microfluidic Biosensors and Actuators, Sci Rep, vol. 6, p. 22237, 2016“.

In this work, summarized in the image extracted from the cited paper (courtesy of Nature-Macmillan Publishers), it is implemented an integral set of hardware, software, and Glassware that enables wireless transmission of sensor data onto the Google Glass for on-demand data visualization and real-time analysis. The platform allows the user to control outputs entered through the Glass, achieving a bi-directional Glass-device interfacing. In this work it is demonstrated the capability of the system in monitoring physical and physiological parameters such as temperature, pH, and morphology of liver- and heart-on-chips.

Such an innovative platform, along with its concept, has set up for the first time a premise in wearable monitoring and controlling technology for a wide variety of applications in biomedicine.

Other results obtained from this Activity arev reported in tfollowing papers:

• L. E. Bertassoni, M. Cecconi, V. Manoharan, M. Nikkhah, J. Hjortnaes, A. L. Cristino, G. Barabaschi, D. Demarchi, M. R. Dokmeci, Y. Yang, and A. Khademhosseini, “Hydrogel bioprinted microchannel networks for vascularization of tissue engineering constructs,” Lab Chip, vol. 14, no. 13, pp. 2202–2211, Jul. 2014
• G. Camci-Unal, D. Cuttica, N. Annabi, D. Demarchi, and A. Khademhosseini, “Synthesis and characterization of hybrid hyaluronic Acid-gelatin hydrogels.,” Biomacromolecules, vol. 14, no. 4, pp. 1085–1092, Apr. 2013
• A. Patel, A. K. Gaharwar, G. Iviglia, H. Zhang, S. Mukundan, S. M. Mihaila, D. Demarchi, and A. Khademhosseini, “Highly elastomeric poly(glycerol sebacate)-co-poly(ethylene glycol) amphiphilic block copolymers.,” Biomaterials, vol. 34, no. 16, pp. 3970–3983, Feb. 2013;
• F. Piraino, S. Selimović, M. Adamo, A. Pero, S. Manoucheri, S. Bok Kim, D. Demarchi, and A. Khademhosseini, “Polyester μ-assay chip for stem cell studies,” Biomicrofluidics, vol. 6, no. 4, pp. 044109–044109–14, 2012

 

Study of ElectroChemiLuminescent sensors for biomolecules

In recent times, there is a lot of interest into green, renewable and possibly low cost bio-resources as an alternative way to produce efficient sensing elements for different kind of sensors. Among them, carbon based sensors are more attractive for the development of biosensors due to their intrinsic biocompatibility. The main objective of this work is to discover highly efficient, cost effective and environmental friendly electrode material for the detection of Ruthenium Tris Bypiridil (Ru(bpy)32+) using ElectroChemiLuminescence (ECL) technique.

The Activity is a historical topic on which MiNES Group has worked, starting from standard metal-based electrochemical cells, passing to innovative material exploitation as Carbon Nanotubes (CNTs), Silicon Carbide, and recently green and low cost carbon-based materials for electrodes as bamboo and pistachio shells.

In general the use of Carbon-based electrodes has been demonstrated to give very interesting results in terms of efficiency and detection limit. Carbon it is also of particular interest for Biomedical applications and some tests have been done functionalizing CNT-based electrodes with DNA probes, for the realization of more efficient DNA sensors.

The work carried out in this field is reported in several International Journals:

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