Absorption-based sensing
Absorption-based sensing is mainly focused on the development of optical fibre sensors for invasive application and on optical sensors coupled to microdialysis for the measurement of pH in the adipose tissue.
As for invasive applications, the general attitude of physicians is to undertake actions which can be easily tolerated by the patient and which introduce a minimum risk for the safety of the patient. From this point of view, non-invasive sensors are definitely preferable to invasive sensors. On the other hand, for several applications, the insertion of optical sensors inside the human body cannot be avoided. In this case, very severe regulations must be satisfied in order to guarantee the safety of patients. Optics can be an actual solution in many applications. The potential of optical fiber sensors for continuously monitoring physical and chemical parameters is enormous. The absence of electrical contacts or of the passage of electrical current in the transduction mechanism is of paramount importance in an area in which the safety of the patient is a fundamental aspect. In the case of invasive applications, physicians can also take advantage of the fact that optical fibres can guarantee unique performances, thanks to their geometrical versatility, easy handling, and high degree of miniaturisation. Optical catheters with a diameter of the order of dozens of micron and probe heads miniaturised up to 1 μm enable physicians to arrive at places inside the human body that would be unthinkable with other sensor technologies.
Attention is focused on the gastroesophageal apparatus and in the course of the activity of the group the following sensors were developed and tested in real clinical settings:
- pH sensor
- sensor for the detection of gastric carbon dioxide
- sensor for the detection of bile-containing reflux
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Continuous monitoring of gastric CO2 |
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As for the measurement in the adipose tissue, measurements were performed on both animal models and on volunteers by using as optical interface a microdialysis catheter capable to have access to the interstitial tissue.
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Projects
COMOCADOF (“Continuous Monitoring of Gastric Carbon Dioxide with Optical Fibres”)
CLINICIP (“Closed Loop Insulin Infusion for Critically Ill Patients”)
Main Publications on the subject
F. Baldini, G. Ghini, A. Giannetti, F. Senesi, C. Trono: A novel optical probe for pH sensing in gastro-esophageal apparatus, Proc. SPIE 7890, Advanced Biomedical and Clinical Diagnostic Systems IX (24-26 January 2011, San Francisco, USA), pp.78901J-78901J6, 2011.
Abstract :Monitoring gastric pH for long periods, usually 24 h, may be essential in analyzing the physiological pattern of acidity, in obtaining information on changes in activity during peptic ulcer disease, and in assessing the effect of antisecretory drugs. Gastro-esophageal reflux, which causes a pH decrease in the esophagus content from pH 7 even down to pH 2, can determine esophagitis with possible strictures and Barrett’s esophagus. One of the difficulties of the optical measurement of pH in the gastro-esophageal apparatus lies in the required extended working range from 1 to 8 pH units. The present paper deals with a novel optical pH sensor, using methyl red as optical pH indicator. Contrary to all acid-base indicators characterized by working ranges limited to 2-3 pH units, methyl red, after its covalent immobilization on controlled pore glass (CPG), is characterized by a wide working range which fits with the clinical requirements. The novel probe design here described is suitable for gastro-esophageal applications and allows the optimization of the performances of the CPG with the immobilised indicator. This leads to a very simple configuration characterized by a very fast response time.
E. Lubian, F. Baldini, A. Giannetti, C. Trono, T. Carofiglio: Solid-supported Zn(II) porphyrin tweezers as optical sensors for diamines, Chem Comm, 46, pp. 3678-3680, 2010
Abstract A melamine-bridged bis-Zn(II) porphyrin dyad covalently attached onto amino-functionalized TentaGel polymer beads or controlled pore glass (CPG) undergoes a reversible and marked colour change from purple to green upon exposure to a biogenic diamine such as cadaverine both in organic and aqueous media.
F.Baldini, A.Giannetti, A.Mencaglia: Optical Sensor for interstitial pH measurements, J. Biomedical Optics, 12 (2), 24024 (2007)
Abstract :An optical fiber sensor for measuring the pH in interstitial fluid is described. Microdialysis is the approach followed for extracting the sample from the subcutaneous adipose tissue. The interstitial fluid drawn flows through a microfluidic circuit formed by a microdialysis catheter in series with a pH glass capillary. The pH indicator (phenol red) is covalently immobilized on the internal wall of the glass capillary. An optoelectronic unit that makes use of LEDs and photodetectors is connected to the sensing capillary by means of optical fibers. Optical fibers are used to connect the interrogating unit to the sensing capillary. A resolution of 0.03 pH units and an accuracy of 0.07 pH units are obtained. Preliminary in vivo tests are carried out in pigs with altered respiratory function.
F.Baldini, F.Feichtner, A.Giannetti, G.Gori, A.A.Mencaglia, V.Pavoni, A.M.Perna, C.Trono: In-vivo characterisation of a microdialysis-based pH sensor, Proc.SPIE 6619, EWOFS’07 - Third European Workshop on Optical Fibre Sensors (4-6 July 2007,Napoli,Italia), pp.661922-1 - 661922-4, 2007
Abstract :A pH sensor based on optical fibres was developed. The analysed sample is the interstitial fluid drawn from the adipose tissue by means of a microdialysis catheter. The pH sensing layer is constituted by a pH indicator, phenol red, directly immobilised onto the internal wall of a glass capillary. The interrogation of the glass capillary is performed by an optoelectronic unit, developed in our laboratory, which makes use of a light emitting diode at 590 nm as source and a photodiode as detector. A suitable animal model was developed and in-vivo tests on pigs were carried out.
F.Baldini, A.Bizzarri, M.Cajlakovic, F.Feichtner, L.Gianesello, A.Giannetti, G.Gori, C.Konrad, A.A.Mencaglia, E.Mori, V.Pavoni, A.M.Perna, C.Trono: Carbon dioxide, oxygen and pH detection in animal adipose tissue by means of extracorporeal microdialysis, Proc.SPIE 6585, Optical Sensors (16-19 Aprile 2007, Prague, Czech Republic) pp.658510-1 - 658510-7 (2007) (ISBN 9780819467133)
Abstract :Typical physiological symptoms can be developed in healthy people under critically ill conditions. pH, pO2 and pCO2 are informative indicators of the conditions of a living system and can be valuable in determining the physiologic status of the critically ill patients. The continuous monitoring of these small molecules into the interstitial fluid (ISF) is a promising approach to reduce diagnostic blood loss and painful stress associated with blood sampling. Microdialysis is the approach followed for the extraction of the sample from the subcutaneous adipose tissue; the drawn interstitial fluid flows through a microfluidic circuit formed by the microdialysis catheter in series with a glass capillary on the internal wall of which the appropriate chemistry for sensing is immobilised. Absorption changes for pH sensor and modulation of the fluorescence lifetime for pO2 and pCO2 are the working principle. Phenol red covalently bound into the internal wall of a glass capillary by means of the Mannich reaction and platinum(II) tetrakis-pentafluorophenyl-porphyrine entrapped within a polymerised polystyrene layer are the chemical transducers used for pH and oxygen detection; the ion pair 8- hydroxypyrene-1,3,6-trisulfonic acid trisodium salt/tetraoctylammonium hydroxide, dissolved in a silicon-based polymeric matrix, is used for the carbon dioxide detection. A suitable hemorrhagic shock model was developed in order to validate clinically the developed sensors in the condition of extreme stress and the obtained results show that the adipose tissue can become an alternative site for the continuous monitoring of pH, pO2 and pCO2.
F. Baldini: In vivo monitoring of the gastrooesophageal system using optical fibre sensors, Anal. Bioanal. Chem., 375, 732-743, 2003
Abstract :In the present paper optical fibre sensors for the detection of foregut diseases are described, in particular, sensors for the detection of bile, carbon dioxide and pH. Bile-containing refluxes are measured by means of a sensor which uses bilirubin as natural marker. The sensor, which is already present on the market, has been clinically validated by various hospitals. The clinically relevant parameter is the exposure time of the stomach/oesophagus mucosa to the bile. When measured in the oesophagus, it has been shown to be closely correlated with the onset of Barrett’s oesophagus or general oesophagitis. Recently, optical fibres have been proposed for the continuous monitoring of carbon dioxide in the stomach: an important parameter in critically ill patients. A clinically validated prototype has shown its superiority in comparison with the traditional method, that is based on gastric tonometry. For the sake of completeness, also gastric pH sensors are considered, although at the moment their development is stationary at the laboratory stage.
F.Baldini, A.Falai, A.R.De Gaudio, D.Landi, A.Lueger, A.Mencaglia, D.Scherr, W.Trettnak: Continuous monitoring of gastric carbon dioxide with optical fibres, Sensors and Actuators B, 90, 132-138, 2003
Abstract An optical fibre sensor for the continuous monitoring of gastric carbon dioxide is described, based on the utilisation of a sensing layer, in which the colour of the layer is dependent on the CO2 concentration. The CO2-sensitive layer consists basically of a dye/quaternary ammonium ion pair, dissolved in a thin layer of ethylcellulose. The sensor was thoroughly characterised in laboratory and its performances were compared with those of Tonocap, the instrument based on gastric tonometry, which is the present method for detecting partial pressure of gastric carbon dioxide. Its measurement range, 0–150 h Pa, its accuracy, 2.5 h Pa, and its response time, less than 1 min, were capable of satisfying the physicians’ requirements for clinical application. The clinical tests, carried out on volunteers and on intensive care patients, showed that the developed sensor is definitely superior to the sensor that is at present available on the market: thanks to its short response time, the optical fibre sensor is able to detect rapid changes in pCO2, currently unknown because of the lack of a tool with which to measure them.
F.Baldini, P.Bechi, S.Bracci, F.Cosi: In vivo optical fibre pH sensor for gastro-esophageal measurements, Sensors and Actuators B, 29 (1-3), pp.164-168, 1995.
Abstract :The present work is concerned with the development of an optical-fibre sensor for monitoring pH in the foregut in the extended range 1.0-8.0. Controlled pore glasses (CPGs),with covalently bound chromophore, are fixed at the end of plastic optical fibres using a proprietary process. A good sensitivity, fast response time, the small dimensions of the probe and the biocompatibility of the materials utilized make the sensor suitable for in vivo measurements.
Patents
F.Baldini, C.Trono: Fiber optic probe and measuring sensor using said probe, European Patent EP 2645931 B1 (07-01-2015)
F.Baldini, S.Bracci, F.Cosi, R.Falciai: Method for fixing vitreous support particles to the tip of a fiber-optic chemical sensor, and sensors so constructed, European Patent EP0633465 (1-11-95)
F.Baldini, S.Bracci, F.Cosi, R,Falciai: Method and apparatus for the immobilization of vitreous supports at the ends of plastic or glass optical fibers for the construction of fiber-optic chemical sensor, USA Patent Number US 5,530,779 (25-06-1996)
R.Falciai, A.M.Scheggi, F.Baldini, P.Bechi: Method of detecting enterogastric reflux and apparatus for the implementation of this method, European Patent 0323816B1 (6-11-91)
R.Falciai, A.M.Scheggi, F.Baldini, P.Bechi: Method of detecting enterogastric reflux, USA Patent Number US 4,976,265 (11-12-1990)
