Jacopo Olivo

Energy Harvesting and Remote Powering for Implantable Biosensors

This paper reviews some popular techniques to harvest energy for implantable biosensors. For each technique, the advantages and drawbacks are discussed. Emphasis is placed on the inductive links that are able to deliver power wirelessly through the biological tissues and enable bidirectional data communication with the implanted sensors. Finally, high-frequency inductive links are described, focusing also on the power absorbed by the tissues.

Fully Integrated Biochip Platforms for Advanced Healthcare

Recent advances in microelectronics and biosensors are enabling developments of innovative biochips for advanced healthcare by providing fully integrated platforms for continuous monitoring of a large set of human disease biomarkers. Continuous monitoring of several human metabolites can be addressed by using fully integrated and minimally invasive devices located in the sub-cutis, typically in the peritoneal region. This extends the techniques of continuous monitoring of glucose currently being pursued with diabetic patients. However, several issues have to be considered in order to succeed in developing fully integrated and minimally invasive implantable devices. These innovative devices require a high-degree of integration, minimal invasive surgery, long-term biocompatibility, security and privacy in data transmission, high reliability, high reproducibility, high specificity, low detection limit and high sensitivity. Recent advances in the field have already proposed possible solutions for several of these issues. The aim of the present paper is to present a broad spectrum of recent results and to propose future directions of development in order to obtain fully implantable systems for the continuous monitoring of the human metabolism in advanced healthcare applications.

Design, development, and validation of an in-situ biosensor array for metabolite monitoring of cell cultures

Conventional pharmaceutical processes involving cell culture growth are generally taken under control with expensive and long laboratory tests performed by direct sampling to evaluate quality. This traditional and well-established approach is just partially adequate in providing information about cell state. Electrochemical enzyme-based biosensors offer several advantages towards this application. In particular, they lend themselves to miniaturization and integration with cheap electronics. In the present work we go through the design, the development, and the validation of a self-contained device for the on-line measurement of metabolites in cell culture media. We microfabricated a sensing platform by using thin film technologies. We exploited electrodeposition to precisely immobilize carbon nanotubes and enzymes on miniaturized working electrodes. We designed and realized the electronics to perform the electrochemical measurements and an Android application to display the measurements on smartphones and tablets. In cell culture media glucose biosensor shows a sensitivity of 4.7 ± 1.3 nA mM(-1)mm(-2) and a detection limit of 1.4mM (S/N = 3σ), while for lactate biosensor the sensitivity is 12.2 ± 3.8 nA mM(-1)mm(-2) and the detection limit is 0.3mM. The whole system was then validated by monitoring U937 cell line over 88 h. Metabolic trends were fully congruent with cell density and viability. This self-contained device is a promising tool to provide more detailed information on cell metabolism that are unprecedented in cell biology.

A Subcutaneous Biochip for Remote Monitoring of Human Metabolism: Packaging and Biocompatibility Assessment

This paper represents the extended version of the conference paper “Developing highly-integrated subcutaneous biochips for remote monitoring of human metabolism” presented at the IEEE Sensors Conference 2012, and presents data on assembly, packaging and short term in vitro and in vivo biocompatibility evaluation of a fully implantable biosensor array. The device was realized integrating three building blocks: 1) a multielectrode platform; 2) an inductive coil; and 3) an integrated circuit. The entire system measures 2.2 mm × 2.2 mm × 15 mm. Corrosion of electronic components and leaking of potentially hazardous substances in the body is prevented with a conformal coating of Parylene C, while an outer package of medical grade silicone was employed to create a soft shell suitable for implantation. Biocompatibility experiments did not show in vitro cytotoxicity in the considered period of 7 days, while comparison between 7 and 30 days in vivo implantations showed significant reduction of the inflammatory response in time, suggesting normal host recovery.

IronIC patch: A wearable device for the remote powering and connectivity of implantable systems

A wearable device to power implanted sensors by means of an inductive link is presented. The system, having size 69 × 40 mm2, is designed to be embedded into a skin patch and located over the implantation area. The system can transfer up to 15 mW within 6 mm in air. Tested with a 17 mm thick beef sirloin placed between the inductors, the device is able to deliver up to 1.17 mW. Downlink communication with the implanted sensors is performed at 100 kbps by using amplitude modulation. Uplink communication is performed at 66.6 kbps by using load modulation. Long range communication between the system and remote devices is enabled by a bluetooth module. The system is powered by two rechargeable lithium-ion polymer batteries and has an autonomy of 10 h in stand-by mode and about 1.5 h in transmitting mode.

New Approaches for Carbon Nanotubes-Based Biosensors and Their Application to Cell Culture Monitoring

Amperometric biosensors are complex systems and they require a combination of technologies for their development. The aim of the present work is to propose a new approach in order to develop nanostructured biosensors for the real-time detection of multiple metabolites in cell culture flasks. The fabrication of five Au working electrodes onto silicon substrate is achieved with CMOS compatible microtechnology. Each working electrode presents an area of 0.25 mm2, so structuration with carbon nanotubes and specific functionalization are carried out by using spotting technology, originally developed for microarrays and DNA printing. The electrodes are characterized by cyclic voltammetry and compared with commercially available screen-printed electrodes. Measurements are carried out under flow conditions, so a simple fluidic system is developed to guarantee a continuous flow next to the electrodes. The working electrodes are functionalized with different enzymes and calibrated for the real-time detection of glucose, lactate, and glutamate. Finally, some tests are performed on surnatant conditioned medium sampled from neuroblastoma cells (NG-108 cell line) to detect glucose and lactate concentration after 72 hours of cultivation. The developed biosensor for real-time and online detection of multiple metabolites shows very promising results towards circuits and systems for cell culture monitoring.

A Study of Multi-Layer Spiral Inductors for Remote Powering of Implantable Sensors

An approach based on multi-layer spiral inductors to remotely power implantable sensors is investigated. As compared to single-layer inductors having the same area, multi-layer printed inductors enable a higher efficiency (up to 35% higher) and voltage gain (almost one order of magnitude higher). A system conceived to be embedded into a skin patch is designed to verify the performance. The system is able to transmit up to 15 mW over a distance of 6 mm and up to 1.17 mW where a 17 mm beef sirloin is placed between the inductors. Furthermore, the system performs downlink communication (up to 100 kbps) and uplink communication based on the backscattering technique (up to 66.6 kbps). Long-range communication is achieved by means of a bluetooth module.

Modeling of printed spiral inductors for remote powering of implantable biosensors

Fully implantable biosensors require small size to be minimally invasive. To avoid embedded batteries, power can be supplied by means of printed spiral inductors located on the skin, close to the implanted devices. Reliable models are required to optimize the design of such inductors. In this paper, a RLC model to describe the electrical properties of printed spiral inductors is proposed. The model is based on the geometrical and physical characteristics of the inductors. The accuracy of the model is finally compared with the experimental measurements.

Optimal frequencies for inductive powering of fully implantable biosensors for chronic and elderly patients

The paper aims at exploring advantages and drawbacks of using high-frequency inductive links to transmit power wirelessly to implanted biosensors. A system with an external transmitting coil located into a skin patch and a receiving coil embedded into a fully implanted biosensor is simulated. The effects of the geometry of the coils on the optimal working frequencies and on the power gain have been analyzed. For applications dedicated to elderly and chronic patients, attention has been posed to the effects on link efficiency of different implantation sites and possible misalignments between the coils.

Glucose and lactate monitoring in cell cultures with a wireless android interface

Advancements in technology can noticeably extend the knowledge of molecular biology for several types of cell cultures. However, at present there is a lack of available systems for real-time monitoring of cell behavior in-vitro. In this paper we propose a sensor for real-time monitoring of glucose and lactate in cell cultures, with the possibility to extend the detection to other metabolites. We explore electrodeposition as a method to precisely immobilize multi-walled carbon nanotubes and different enzymes on multiple Au electrodes in a single step. The sensor performs amperometric measurements and is connected to portable devices, such as smartphones and tablets, by means of an Android application. The application, named BlueCells, communicates to remote devices via Bluetooth and enables the user to select the species to be monitored and the measurement setup. Finally, it enables online monitoring of the species directly on the device screen. The whole system has been tested by chronoamperometries of glucose and lactate in cell culture media. The sensor achieves a sensitivity of (4.67 ± 1.26) nA=(mM·mm2) and a detection limit of (1.41 ± 0.90) mM for the glucose, while it results in a sensitivity of (12.16 ± 3.8) nA=(mM·mm2) and a detection limit of (0.28 ± 0.17) mM for the lactate.