The present invention relates to the field of medical devices, and in particular, measuring physiological parameters of blood based on photon density to sense concentration of partial pressure oxygen in arterial blood. BACKGROUND OF THE INVENTION

In medical perspective, oxygen level in blood of a patient should ideally be monitored continuously for determining the general health of the patient. It is impractical to determine the oxygen level in blood with blood sampling regularly and withdrawing via an arterial blood sample from the patient. The condition is severe when the patients are elderly suffered from collapsed veins, or infants at average may only have 125 cm ³ of blood. Currently, amperometric or galvanic method oxygen sensors are bulky and inefficient due to electrical interference. This could lead to a misleading data generation. While development an optical oxygen sensor may solved the above issues, the continue developments of the optical oxygen sensor have progressed rapidly in improving sensitivity, selectivity and response time towards the oxygen sensor. These factors are important for the sensor to measure accurately and quantitatively of many acutely ill hospitalized patients. However, none of these technologies can improve sensitivity, selectivity and response time towards the oxygen sensor. The present invention provides a system having an optical oxygen sensor and combination with fiber optics and planar waveguide platforms have made dramatic progress in the appearance, sensitivity, selectivity, response time through direct and indirect measurement detection technique using chemical indicator. The present invention further provides a considerable reduction of materials with even greater efficiency and economically during operation. SUMMARY OF THE INVENTION

The present invention provides a system for measuring oxygen concentration in blood comprising a light source module to provide a collimated ultra-violet light beam and split the ultra-violet light beam into a first light beam to generate photon to stimulate to a sensor material and a second light beam to generate an entangled photon pair; a detector module having a first detector to determine the photon reflected from the sensor material upon sensing the oxygen in blood and a second detector to determine a first photon from the entangled photon pair as a reference; a sensor material receiving a combination source of photons of a second photon from the entangled photon pair and the photon from the first light beam to sense a presence of oxygen in blood and providing an optical response via reflected photon to the first detector; and a controller to synchronize the light source module and determine the oxygen concentration in blood by providing a comparison between the first photon from the entangled photon pair as a reference and the optical response via reflected photon to the first detector.

In one of the embodiment of the present invention, a beam splitter is provided to split the ultra-violet light beam. In yet another embodiment of the present invention, the first light beam to stimulate sensor material is directed via to a reflecting mirror to guide and align the first light beam to an optical shutter and an optical coupling before reaches to a fiber.

In another embodiment of the present invention, the fiber is used as a waveguide to guide the first light beam to the sensor material.

In one of the embodiment of the present invention, the optical shutter is controlled by the controller which allows the first light beam pass through for a predetermined duration to excite the sensor material and to block the optical shutter when the sensor material is fully excited.

In another embodiment of the present invention, the second light beam is collimated to a non-linear crystal Beta Barium Borate (BBO) Type 1 and triggered Spontaneous Parametric Down-Conversion (SPDC) process to generate the entangled photon pair. The entangled photon pair consists of a signal photon source measured by a second detector to determine a first photon from the entangled photon pair as a reference; and an idler photon source in combination with the photon from the first light beam to sense a presence of oxygen in blood.

In another embodiment of the present invention, the sensor material is a reagent-mediated chemical sensor with a viologen compound to sense presence of oxygen molecule and the ratio between the first photon from the entangled photon pair as a reference and the reflected photon to the first detector is measured by average photon per pulse according to Poison distribution.

A method of measuring oxygen concentration in blood using comprising generating an entangled photon pairs which each photon in a pair have the same exact quantum state by a light source module; detecting a first photon source from one of the generated photon pair by a first photon detector as a reference; guiding a second photon source from generated photon pair to a sensor material with viologen compound; absorbing the incoming photons when presence of oxygen molecules in blood by the sensor material and reflecting back the photons to a second photon detector when absence of oxygen molecules; synchronizing the first photon detector with the second photon detector by a controller to calculate amount of photon absorption by the sensor material; comparing the detection measurement by the controller between the photon pair generated by entanglement at the first photon detector and second photon detector and determining on the oxygen concentration in blood by measuring the reflected photon.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated in and constitute a part of the specification, illustrate embodiments of the invention and, together with the description, serve to explain the principles of the invention.

Figure 1 illustrates a system for measuring oxygen concentration in blood of optical configuration setup for the photon counting measurement in optical absorption solid state sensor using entangled photon source in accordance of the present invention. Figure 2 illustrates a flow chart of a method of measuring oxygen concentration in blood using the system in accordance of the present invention.

DETAILED DESCRIPTIONS OF THE INVENTION

The present invention will now be described in detail in connection with specific embodiments with reference to the accompanying drawings.

Optical oxygen sensor and combination with fiber optics with planar waveguide platforms have made dramatic progress in the appearance, sensitivity, selectivity, response time through direct and indirect measurement detection technique using a chemical indicator.

In general, some analyte can response directly to the chemical indicator and use optical way to measure and quantify the analyte concentration. However, oxygen has no convenient intrinsic optical property such as absorption or luminescence when using chemical indicator. Therefore the alternative option is to use a reagent mediated chemical sensor. In the reagent mediated sensing system, a change in the optical response of an intermediate agent which usually an analyte-sensitive dye molecule corresponds to the analyte concentration. The present invention describes a system to sense concentration of partial pressure oxygen in arterial blood. The reagent-mediated chemical indicator uses solid form viologen compound and attaches onto a distal end of a fiber optic. Viologen compound is Ν,Ν'- disubstituted -4,4'-dipyridinium based salt. A viologen, such as dibenzyl viologen diffuse away if exposed to water but may be suspended in a polar polymer, such as polyvinyl pyrrolidone) or poly(vinylbenzylchloride) to produce insoluble poly(benzylviologenco- benzy (chloride). These polymers are highly charged and very polar, they interact significantly with water. Hence, this viologen compound is stable in an aqueous environment over period of time. This chemical compound i.e. viologen has been characterized experimentally by Roger A. Wolthuis et. al (1992) which able to respond to the partial oxygen concentration. The sensing mechanism based on optical absorption with presence oxygen, after stimulated by ultraviolet light is illustrated to as follows: >- -<"·-·€Η -"'- Κ ' ";::;:.::::; '·*

Source: Roger A. Wolthuis et. al (1992)

Ultra-violet light transforms the viologen dication, having two positive charges per molecule to a colored viologen cation with single positive charge per molecule. This viologen cation transforms back to viologen dication by absorbing energy supplied by a light source over 600 nm of wavelength with presence of oxygen molecule with energy around 3.31 E-19 J. The oxygen molecules as sensed in the present invention are based on dynamic quenching principle. Dynamic quenching is time dependent and occurred within at an excited state life time of viologen compound.

Oxygen molecule is a collisional quencher. Dynamic quenching does not induce complex formation. The viologen compound and quencher collided creates viologen cation, inducing loss of energy and the two molecules again separated into viologen dication while absorbing the photon (at 600 to 650nm wavelength). When more oxygen molecules quench with the viologen compound molecules, more photons will be absorbed. (J. R. Albani 2007, Roger A. Wolthuis et. al 1992).

The experimental results show that the relationship between the optical absorption and the reflected supplied over 600nm wavelength light source (Roger A. Wolthuis et. al 1992). Therefore, this relationship concluded that the amount of energy absorbed optically as supplied is monitored by the reflected light detected. The present invention works on the optical configuration and detection measurement of supplied photon source while monitoring precisely the partial oxygen concentration in real time based on photon counting detection.

In general, single photon source generated by entangled photon pair through spontaneous parametric down conversion (SPDC) obeyed poison or sub-poison distribution. The formula for this is as follows: u ⁿ e ^~ "

(w. //) = - , " = 0, 1.2.. where, P is the distribution probability ,

n is number photon,

μ is mean photon number

Example for μ=0.1 , the probability of detecting photon, P (n >0) = 1 - P (n=0) since the detector could not differentiate single photon or multiple photons

Photon number, n

Entanglement photon pair namely signal and idler used in the present invention has exactly same frequency and phase, generated naturally when a high energy wavelength is pumped onto non-linear crystal such as Lithium Niobate, LiNb0 ₃ or Beta Barium Borate, BBO and transmit a pair of lower energy wavelength.

The ratio between generated photon source from the entangled photon pair and the reflected photon beam from the viologen compound is measured by average photon per pulse according to Poison distribution with other parameters such as time bin, quantum efficiency of the single photon detector, quantum yield of sensor material which requires to be characterized accordingly. Photon propagation is generally dictated by scattering and absorption in the medium through which the waves are moving. Like other waves, photon density waves undergo refraction, diffraction, interference, dispersion, attenuation, and so forth.

Figure 1 illustrates a system for measuring oxygen concentration in blood of optical configuration setup for the photon counting measurement in optical absorption solid state sensor using entangled photon source. The system for measuring oxygen concentration in blood comprising a light source module 100 to provide a collimated ultra-violet light beam and split the ultra-violet light beam into a first light beam to generate photon to stimulate to a sensor material 300 and a second light beam to generate an entangled photon pair, a detector module 200 having a first detector to determine the photon reflected from the sensor material 300 upon sensing the oxygen in blood and a second detector to determine a signal photon source from the entangled photon pair as a reference, a sensor material 300 receiving a combination source of photons of the idler a second photon source from the entangled photon pair and the photon from the first light beam to sense a presence of oxygen in blood and providing an optical response via reflected photon to the first detector and a controller 400 to synchronize the light source module and determine the oxygen concentration in blood by providing a comparison between the first photon from the entangled photon pair as a reference and the optical response via reflected photon to the first detector.

The light source module begins with a single light source 101 triggered by the controller 400 to provide collimated ultra-violet (UV) at 325nm wavelength light beam to the 50/50 beam splitter 102 which splits the light beam into two light beam with same intensity. One of the splitted UV light beam is used to excite the sensor material 300 is guided by a mirror 103 to pass through an optical shutter 104 before coupled using an optical coupling 105 to the fiber. The fiber used in the present invention as a waveguide to guide the splitted UV light beam to the sensor material 300. The sensor material 300 is a reagent-mediated chemical sensor with a viologen compound at the excited state to sense presence of oxygen molecule.

The optical shutter 104 is controlled by the controller 400 which only allows the UV light beam pass through for a period of time to the extend to excite the sensor material 300. The controller 400 is then triggered the optical shutter 104 to block the UV beam from further passing through when the sensor material 300 is fully excited.

Meanwhile, the other UV light beam collimated to a non-linear crystal, 106 Beta Barium Borate (BBO) Type 1 and triggered Spontaneous Parametric Down-Conversion (SPDC) process to generate the entangled photon pair that is a signal photon source and an idler photon source at lower energy 650nm wavelength due to conservation of energy principle. The signal photon source from the entangled photon pair coupling to a fiber is delivered via an optical coupling 107 to a spectral filter 204 before measured by a single photon detector 203. The controller 400 triggered the photo detector 203 to open detector detection window and subsequently calculates the average photon number per pulse based on poison distribution. The idler photon source from the entangled photon pair coupling to a fiber is delivered to the optical coupling 107 to the sensor material 300. While the fiber for idler photon source combined with the fiber which delivers UV light beam to form into a single fiber. This single fiber is capable to deliver both UV light beam and the idler photon source from the entangled photon pair in a same fiber tip coated with sensor material 300. Another fiber used to couple from sensor material 300 used to deliver the idler photon reflected from sensor material to the single photon detector 201. However, a combination of a single fiber, a bifurcated fiber or a trifurcated fiber can be used to couple the light beam from optical coupling 105, 107 and a first detector 201 onto the sensor material 300. A spectral filter 202 used to allow photon at the wavelength at 650 nm to pass through before reaching the single photon detector 201.

It is known to the person skilled in the art that the photon and oxygen are two different mediums. Therefore, in the present invention, a reagent mediated chemical sensor such as the viologen compound and the like is used. The change in optical response (by absorbing the photon at the presence of oxygen molecules) of this viologen compound corresponds to the oxygen concentration. In operation, the light source module 100 generates an entangled photon pairs which each photon in a pair have the same exact quantum state as illustrated in Figure 2. The signal photon source from entangled photon pair 107 is detected by the second photo detector 203 as a reference. While the idler photon source from generated entangled photon pair is guided to the sensor material 300 such as the viologen compound. The sensor material 300 absorbs the incoming idler photon from entangled generated photon source when presence of oxygen molecules and reflects back the photons to first detector 201 when absence of oxygen molecules. The first photo detector 201 is synchronized with second photo detector 203 by the controller 400 in order to calculate amount of photon absorption by the sensor material 300. During comparison, the detection measurement by the controller 400 between the photon pair generated by entanglement 107 at second photo detector 203 and first photo detector 201, is calculated and determined on the oxygen concentration by measuring the reflected photon. The photon absorption by sensor material 300 is calibrated to the different partial oxygen concentration value to setup as the system prior to use for accuracy and precision measurement purposes.

The entangled photon source obeyed Poisson distribution when synchronizing "pulse" or detecting photons present at a preset time window. During this detection window, the electronic controller will trigger the single photon detector such as Avalanche Photo Diode (APD) or Photo Multiplier Tube (PMT) in receiving any incoming photons. n=3 n=1 n=0

Entangled photon

source , * » ,

I 1 I 1 I 1 I 1 Gating by the t t„. ₂ t„., t„ detector

Table 1 below depicts the calculated model in measuring oxygen concentration. While the second detector acts as a reference and receives the incoming photons directly from entangled photon pair source, the first detector detects the incoming photons from the sensor material. If the oxygen molecules presence, the sensor material absorbs the photon supplied by the entangled pair source and no incoming photons reflect back from the sensor material. The sum result shows the oxygen concentration at given time period, t _n and any error result is discarded from the table.

Table 1

One of the advantages of the present invention is that the system having an optical oxygen sensor and combination with fiber optics and planar waveguide platforms have made dramatic progress in the appearance, sensitivity, selectivity, response time through direct and indirect measurement detection technique using chemical indicator. Furthermore, the system of the present invention is avoided from various types of noise and interference which creates inaccuracies. For example, electrical noise, physiological noise, and other interference can contribute to inaccurate blood flow characteristic estimates.

The foregoing embodiment and advantages are merely exemplary and are not to be construed as limiting the present invention. The description of the embodiments of the present invention is intended to be illustrative and not to limit the scope of the claims and many alternatives, modifications and variations will be apparent to those skilled in the art.

REFERENCES:

1. Wolthuis RA, McCrae D, Hartl JC, Saaski E, Mitchell GL, Garcin K, Willard R. 1992.

Development of a medical fiber-optic oxygen sensor based on optical absorption change. IEEE Transactions on Biomedical Engineering. 39(2): 185-93.

2. J. R. Albani,2007. Principles and applications of fluorescence spectroscopy.

Blackwell Publishing.