Course: Nanotechnology and Nanosensors by Prof. Hossam Haick

Transcription

1 Course: Nanotechnology and Nanosensors by Prof. Hossam Haick FINAL PROJECT: SMART GLUCOSE-SENSITIVE NANOSENSOR Student: Antonella D'Alessandro

2 Student's short biography: Assistant Professor of Construction Science, Department of Civil and Environmental Engineering, University of Perugia. She currently teaches Laboratory of Structural Analysis and Design. She graduated cum laude in Civil Engineering at University of Perugia in She received her PhD in Civil Engineering in Thesis: "The Use of Nanotechnologies for the Production of Strain- Sensitive Cementitious Materials". She won in 2014 the ACI Italy Chapter-Federbeton Award "Innovation in Concrete Structures and Cementitious Materials". Research topics: Self-sensing cement-based nanocomposites, Innovative materials for constructions, Structural Health Monitoring, Fire engineering. Some papers: 1) A.D'Alessandro, F.Ubertini, A.L.Materazzi, M.Porfiri, S.Laflamme. "Electromechanical Modelling of New Nanocomposite Carbon Cement-based Sensors for Structural Health Monitoring"StructHealthMonit(2014) 2) S.Laflamme, F.Ubertini, H.Saleem, A.D'Alessandro, A.Downey, H.Ceylan, A.L.Materazzi. "Dynamic Characterization of a Soft Elastomeric Capacitor for Structural Health Monitoring"ASCE(2014) 3) F.Ubertini, S.Laflamme, H. Ceylan, A.L.Materazzi, G.Cerni, H.Saleem, A.D'Alessandro, A.Corradini. "Novel Nanocomposite Technologies for Dynamic Monitoring of Structures: a Comparison between Embedded and Surface Sensors" SmartMaterStruct(2014) 4) F.Ubertini,. A.LMaterazzi, A.D Alessandro, S.Laflamme. "Natural frequencies identification of a reinforced concrete beam using carbon nanotube cementbased sensors"engstruct(2014) 5) A.L.Materazzi, F.Ubertini, A.D Alessandro, "Carbon nanotube cement-based transducers for dynamic sensing of strain"cemconcrcomp(2013) 6) A.D'Alessandro, F.Ubertini, A.L.Materazzi, M.Porfiri. "Electrical Modelling of Carbon Nanotube Cement-based Sensors for Structural Dynamic Monitoring"AIP(2014) 2

3 Table of content: Student's short biography...2 Abstract...4 Project's goal...4 Introduction...5 Literature review...6 Project description...8 Conclusions and recommendations...9 References

4 Abstract My project concerns a smart Glucose-sensitive nanosensor to better control glucose levels in blood, in a non invasive way. It could be as an invaluable tool in the treatment of diabetes. The current invasive method makes it difficult for diabetic patients to perform frequent blood glucose measurements and maintain better control of their glucose levels, crucial in reducing the risks of complications. The objective of this project is to investigate the problems of common glucose sensors, to provide deeper quantitative understanding to the challenges related to and to propose a new smart device to overcome present issues. The recent development of nanotechnology has allowed the occurrence of new interesting tools and materials. Nanomaterials and nanosensors offer some significant advantages owing to their small size. High specific surface allows larger signals, better catalysis and the more rapid movement of analyte through sensors, and enhances optical characteristics, as quantum dot fluorescence, gold nanoparticle quenching. Project's goal The final project's goal is to develop a new type of glucose sensors with enhanced properties, non invasive and easy to use, utilizing the new materials and instrumentations provided by nanotechnology. These novel sensors could be very useful for diabetes patients and for their health control strongly related to glucose fluctuations in blood. Smart glucose sensors could improve the quality of life significantly for hundreds of millions of people in the world. 4

5 Introduction Diabetes is a growing worldwide issue. In the United States alone, there are 25.8 million affected patients. The annual cost of medical treatment and indirect for diabetic patients is $174 billion. The negative complications of diabetes could be avoided through a constant control of the values of glucose in the blood. Many of these patients are instructed to monitor closely their blood glucose levels to manage the disease. It is extremely important to control the levels of glucose in the blood many times as possible. Some complications linked to badly controlled diabetes (High values of glucose in the blood) are eye complications, foot complications, skin complications, hypertension, mental health, hearing loss, gastroparesis, nephropathy, stroke, infections, healing of wounds. On the other hand, very low blood sugar levels may cause some symptoms, such as weakness, fatigue, extreme thirst and even fainting. There are several tools for patients with diabetes to manage and monitor their condition but none of them is perfect. At present the main type of control is carried out directly in a sample of blood. Therefore, patients should take a small amount of blood to carry out the control, with evident disadvantages. The pain associated with this technique can discourage people from keeping tabs on their glucose regularly. Self-monitoring results essential for the regulation of glucose levels as close to normal as possible, with a frequency of controls of more than three times a day. Bypassing the limitations of the actual methods of measurement of glucose with less invasive systems, the living conditions of a large number of patients can improve. The ideal solution would be a small sensor, easy to use and change and minimally invasive. Nanotechnology could be useful for glucose sensors due to different reasons and applications. First, the nanoscale dimensions of possible sensor components, and secondly for the enhanced properties of nanoscale elements. 5

6 Literature review In recent years, there has been a rise in the development of nanotechnology for drug delivery. One interesting topic is diabetes care. Nanotechnology has been incorporated into glucose sensors because sensors can be designed incorporating a nanomaterial or they could have nano dimensions. These sensors, owing to their size, would be implanted if used for continuous monitoring. These sensors offer some advantages over traditional sensors for continuous monitoring: they would be injectable, which could lead to the easier administration of the sensing system than the current implantation approach. Additionally, because of the small size of these sensors, they could potentially avoid the foreign body response of the immune system and they have longer useful lives. The most common application of nanotechnology for sensors in diabetes is the use of nanomaterials to assist the standard enzymatic electrochemical detection of glucose. Wang provided an overview of work on electrochemical glucose biosensors. A review by Pickup and colleagues, concerning nanomedicine for diabetes care, tksal about nanosensors. CNTs can also be coupled with other nanomaterials or polymers to form nanocomposites for glucose detection. A variety of nanostructured electrodes can improve conventional macrostructured electrodes. For instance, zinc oxide deployed as nanowire or nanotube arrays has been used for glucose detection. Magnetic nanoparticles, commonly made from iron oxide, have also been used for glucose sensors. The magnetic nature of these nanoparticles simplifies the assembly of GOx-labeled nanoparticles onto the electrode. Some technical difficulties are identified to be those caused by complex interferences from other physiological variables and the weak near infrared glucose signals. Thus, the success of such a method hinges on adequately isolating the glucose signals from among the interferences. These sensors are a radical change from current continuous monitoring sensors, and there is little clinical data on these systems, so further research is needed before these nanosensors can be of use to patients. For there reasons such new nano materials and nano devices are not already available to diabetes patients. Most of them still perform a discontinuous control of their glucose levels in the blood. 6

7 Even if new ways to measure glucose levels in real-time throughout the day and night are available ( they still own downsides. Above all, the available sensors produce a hole in the skin which leaves a mark for a certain period of time, may cause infection and scarring and has to move after a few days. Also, you need a special tool to put it correctly. 7

8 Project description A glucose-sensitive nanosensor could be implanted in diabetic patients for an in vivo continuous monitoring of glucose level, bypassing some disavantages of the current terapy of this disease. Electrochemical detection technologies represent a large proportion of research into glucose detection and dominate the field of commercially available sensors. However, for in vivo continuous monitoring, fluorescence-based sensors offer several advantages. Semiconductor Quantum Dots have very good optical properties and are suitable for sensors. They could interact with glucose GOx. Their luminescence is reduced by the originated hydrogen peroxide, in presence of glucose. This allows to recognize the glucose concentration with colorimetric quantification. New nano glucose sensors could be fabricated through attachment of GOx to a QD reporter. In the presence of glucose, the enzyme generates hydrogen peroxide, which quenches the QD, providing an optical signal change proportional to glucose concentrations. Nanosensors is synthesized to contain glucose recognition elements and reporter molecules. In the absence of glucose, the binding of the glucose recognition elements with the reporter molecules result in the formation of fluorescent complexes. In the presence of glucose, the glucose recognition elements bind glucose, which displaces them from a complex with the reporter molecules, and thus, leads to a decrease in fluorescence intensity. Such sensors could be implanted into the skin, as a patch, resulting in a greater ease of use. The innovation of this novel sensor compared to available sensors concerns the realization of novel nano engineered materials improving the enzymatic activity and the stability. Nanomaterials would be nanoinclusions into these sensors, to increase surface area and improve catalytic action. This could be accomplished through the use of single types of nanomaterials such as CNTs, or multiple nanomaterials working together. 8

9 Conclusions and recommendations Nanoscale sensors have the potential to drastically improve continuous glucose monitoring capabilities and improve diabetes patient quality of life. Continuous monitoring, like that achieved by some of the systems discussed before, is a necessary part of this long-term goal. Implanted sensors minimize patient inconvenience and pain. The nanomaterials and nanofabrication techniques improve sensitivity as well as yield extremely low limits of detection. Although one sensor has been demonstrated in human plasma doped with extremely low concentrations of glucose, there is little other research on the clinical applicability of these sensors or improvement over commercial sensors for the care of patients with diabetes. In addition to the cost, other questions remain about the ability for these approaches to impact clinical care, their biocompatibility and sensor lifetime. Some other issues that need to be addressed include the possibility of the body mounting an immune response against the nanosensor. In addition, there may be a delay time in measuring blood glucose levels since the skin implantation does not directly sample the blood. Lastly, there needs to be clinical evidence that this nanosensor is as much efficient as other monitoring methods currently available to diabetes patients. 9

10 References Wu, P. et al.(2010) Conjugation of glucose oxidase onto Mn-doped ZnS quantum dots for phosphorescent sensing of glucose inbiological fluids. Anal. Chem.82, J. W. Chen (2013) The Potential of Nanotechnology for Diabetes Management Akin J, Materials for Drug Delivery. Harvard University Science in the News Flash Newsletter. Li, Y.et al.(2009) Glucose biosensor based on the room-temperature phosphorescence of TiO2/SiO2 nanocomposite.biosens. Bioelectron. 24, Tang, B. et al. (2008) A new nanobiosensor for glucose with high sensitivity and selectivity in serum based on fluorescence resonance energy transfer (FRET) between CdTe quantum dots and Au nanoparticles.chemistry - A European Journal14, Cash, K.J. and Clark, H.A. (2010) Nanosensors and nanomaterials for monitoring glucose in diabetes Trends in molecular medicine 16(12) Wang, J. Electrochemical glucose biosensors. Chem. Rev. (Washington, DC, U.S.). 2008; 108: Pickup, J.C. et al. Nanomedicine and its potential in diabetes research and practice. Diabetes Metab. Res. Rev. 2008; 24: Nano-yarn carbon nanotube fiber based enzymatic glucose biosensor. Zhu, Z.G. et al. Nanotechnology. 2010; 21 SiO2 coated Fe3O4 magnetic nanoparticle dispersed multiwalled carbon nanotubes based amperometric glucose biosensor. Baby, T.T. and Ramaprabhu, S. Talanta. 2010; 80: A fast and sensitive potentiometric glucose microsensor based on glucose oxidase coated ZnO nanowires grown on a thin silver wire. Ali, S.M.U. et al. Sensors and Actuators B-Chemical. 2010; 145: Hollow spherical nanostructured polydiphenylamine for direct electrochemistry and glucose biosensor. Santhosh, P. et al. Biosens. Bioelectron. 2009; 24: Synthesis of magnetic nanoparticles composed by Prussian blue and glucose oxidase for preparing highly sensitive and selective glucose biosensor. Li, J.P. et al. Sensors and Actuators B-Chemical. 2009; 139: