| Optical-chemical and biochemical sensing is being | | | | patient, but they also offer physicians the right tool |
| researched extensively all over the world, and these | | | | for correct and rapid diagnosis.6 High-density optical |
| sensors are finding an increasing number of | | | | microarray platforms have already been developed: |
| applications in industry, environmental monitoring, | | | | thousands of 50–100µ m spots have been |
| medicine, biomedicine, and chemical analysis.(fiber | | | | deposited on glass slides or on microliter plate wells, |
| optic patch cable )with fiber optic patch cable widely | | | | each of which carry a different chemistry for the |
| used.The main physical phenomena exploited for | | | | detection of different parameters. A high-density |
| optical chemical sensing are absorption and | | | | optical fiber microarray platform has also been |
| fluorescence, although chemical luminescence, Raman | | | | developed:7 this uses a 1mm-diameter optical fiber |
| scattering, and plasmon resonance have also been | | | | bundle that contains 50,000 individually-addressable |
| used. Optical sensors are mainly based on | | | | 3µm-diameter fibers. |
| amplitude-modulation: the intensity of the light is | | | | Novel approaches |
| directly modulated by the parameter being | | | | Two new approaches have recently been proposed: |
| investigated (which has optical properties) or by a | | | | a ‘mechanical’ approach, based on the use |
| chemical transducer whose optical properties vary | | | | of microcantilever sensors, and a resonant approach, |
| with the concentration of the parameter under study. | | | | in which the optical interaction takes place in a |
| In the case of fluorescence, time- or | | | | resonant microcavity. |
| phase-modulation is often preferred to | | | | The use of microcantilevers as transducers for |
| amplitude-modulation, since sensor response is | | | | chemical and biochemical sensing has only become |
| practically unaffected by the photobleaching of the | | | | widespread in the last few years, mainly due to their |
| chemical transducer in the latter case.(fiber optic | | | | use in the development of microsensor arrays.7 |
| patch cable ) | | | | However, the invention of scanning-force |
| Health-care is unquestionably the application field | | | | microscopy, in which the microcantilever plays the |
| which seems to have the most potential for future | | | | fundamental role of force transducer, goes back to |
| development.2,3 Optical biosensors are finding | | | | the 1980s. The idea is quite simple: the surface of the |
| ever-increasing applications in different branches of | | | | cantilever, a rectangular thin beam clamped at one |
| medicine for several reasons. | | | | end, is chemically modified so that it can react with |
| Invasive sensors | | | | specific compounds. The mass deposition that follows |
| First of all, miniaturization (by using fiber optic patch | | | | the chemical reaction causes a stress, and this leads |
| cable , for instance) can make it possible to directly | | | | to a detectable bending of the cantilever (see Figure |
| measureme biomedical parameters by allowing the | | | | 2). Recent work has shown the capability of these |
| probe to be placed either in contact with human skin | | | | micromechanical structures to investigate DNA |
| or inside the body. Optical catheters with diameters | | | | hybridization and antibody-antigen recognition. |
| of the order of dozens of microns, and probe heads | | | | Figure 2. Sketch of the working principle of a |
| miniaturized to a few microns, enable physicians to | | | | microcantilever-based chemical sensor. A single |
| arrive at places inside the human body that would be | | | | cantilever is typically 500µm long and 200µm wide. |
| unthinkable with other sensor technologies. | | | | Displacements of the order of few nanometers can |
| In collaboration with Joanneum Research (Graz, | | | | be detected. |
| Austria), we have developed an optical fiber sensor | | | | In terms of resonance, dielectric microspheres with |
| for the continuous monitoring of carbon-dioxide partial | | | | diameters in the 50–300µm range are used as |
| pressure in the stomach.4 The sensor is based on | | | | optical cavities. The principle is based on the |
| the color change of a CO2-sensitive indicator layer. | | | | frequency shift of the resonance modes caused by |
| This layer is attached to the distal end of an optical | | | | adsorption/binding of the chemicals under |
| fiber positioned in the stomach or in the esophagus. | | | | investigation on the surface of the microspheres (see |
| The optoelectronic unit is connected to a laptop that | | | | Figure 3)8 For a silica-glass microsphere with a |
| is used for data acquisition and processing, and for | | | | diameter of 200µm, the distance the resonant |
| calibration (see Figure 1). | | | | wave covers is roughly 20m: the light mode |
| Figure 1. Sketch of an optical sensor for CO2 | | | | circumnavigates the equator roughly 60,000 times. |
| detection in the stomach or oesophagus. | | | | This potentially makes the approach very sensitive, |
| Another example of the potential of optical sensors | | | | since the light interacts with the external medium |
| in biomedicine is the development of an intelligent | | | | along a very great distance. From a theoretical point |
| system for improved monitoring of critically ill patients. | | | | of view, even single-protein detection is possible. |
| This is the aim of the four-year EU-funded project | | | | Figure 3. Sketch of the working principle of a |
| CLINICIP (Closed Loop INsulin Infusion for Critically Ill | | | | microcavity resonator. Light from a tunable laser |
| Patients) that began in 2004.5 The system under | | | | diode, modulated in wavelength, is coupled to a |
| development includes optical sensors for the | | | | single-mode laser fiber. The resonant modes of the |
| determination of glucose, pH, pO2 and pCO2. | | | | microcavity are excited by means of evanescent |
| Microdialysis is used to extract samples from either | | | | coupling. |
| the subcutaneous adipose tissue or blood: the drawn | | | | Conclusions |
| sample flows through a microfluidic circuit formed by | | | | Optical sensors are under continuous development |
| the microdialysis catheter in line with the sensors, | | | | and offer physicians reliable and efficient tools for |
| with the chemical transducers on the internal walls of | | | | diagnoses. The instruments already available on the |
| the glass capillaries. | | | | market, and the many systems now at advanced |
| Sensor arrays | | | | stage in labs, demonstrate that optical sensors are |
| Another important possibility for clinical diagnostics is | | | | some of the best options for scientists and |
| the development of multiarray biochips for the | | | | physicians when in-vivo continuous monitoring is |
| analysis of multiple parameters in parallel. Not only are | | | | necessary. |
| these essential for immediate rapid screening of the | | | | |