ABSTRACT
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.
Subject(s)
Biosensing Techniques/instrumentation , Cell Culture Techniques/instrumentation , Culture Media/metabolism , Glucose/metabolism , Lactic Acid/metabolism , Culture Media/chemistry , Electrochemistry/instrumentation , Equipment Design , Glucose/analysis , Humans , Lactic Acid/analysis , Limit of Detection , Microelectrodes , Nanotubes, Carbon/chemistry , Nanotubes, Carbon/ultrastructure , U937 CellsABSTRACT
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.
Subject(s)
Electric Power Supplies , Prostheses and Implants , Telemetry/instrumentation , Animals , Cattle , Equipment Design , Humans , MeatABSTRACT
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.
Subject(s)
Biosensing Techniques , Microchip Analytical Procedures , Monitoring, Physiologic , Prostheses and Implants , Animals , Biomedical Engineering , Biotechnology , Delivery of Health Care , Humans , NanotechnologyABSTRACT
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.
