Field of Invention
The invention relates to a non-invasive photo-acoustic electronic apparatus adaptable to measure the concentration of body fluid components, in particular blood glucose levels.
Background of Invention
Hyperglycemia has been identified as the primary cause of the severe complications associated with diabetes, including premature death, blindness, kidney failure, amputations, heart disease and stroke. Diabetic patients require frequent monitoring of blood glucose at regular and short intervals for management of diabetes mellitus.
Such periodical monitoring plays an important role in patient management and helps physicians to make quick decisions including dietary adjustments, exercise patterns and medication prescriptions, etc. This way the giucose levels are kept within the prescribed limits to avoid the situations of both hyperglycemia as well as hypoglycemia.
According to American Diabetes Association, patients who adhere to intensive treatment (tight control) i.e. intensively monitor and maintain blood glucose level within a nearly normal range, reduce their chronic complications by 50-75%. Thus, in the surgical situations due to other complications, the glucose level monitoring becomes a highly critical element.

Commonly used current glucose level measurement methods require a blood sample for each measurement for analyzing it chemically off-line and reading the result optically. However, such off-line measurement may cause cell contamination, can be time consuming, labour intensive, and may not reflect the real-time status of the glucose. The use of needles and disposal of used blood samples and chemicals pose health risks and possibility of spread of diseases like hepatitis, HIV. Further, the patient is put to inconvenience each time a blood sample is required for analysts.
Although self-monitoring of blood glucose (SMBG) monitors have revolutionized the management of diabetes in which a drop of blood is collected for chemical analysis by finger lancing, but the discomfort, inconvenience and high recurring cost associated with such measurements are barriers for effective compliance.
There are non-invasive techniques employed for measuring biological constituents which offer enormous benefit compared to invasive one. This is due to the fact that not only is this method painless but also eliminates the requirement of any sample preparation before measurement. Most of the prior art techniques for non-invasive measurement are based on measurement of optical transmittance or reflectance due to easy availability of miniaturized optical sources and detectors. They are low cost and do not require any consumable reagent and are harmless to the tissue.
The known non-invasive techniques for measuring blood glucose are mostly based on measurement of transmittance and reflectance in the near infrared (NIR) range, Raman spectroscopy, spatially resolved diffused reflectance and

photoacoustic (PA) methods. Compared to other optical methods, PA method offers higher sensitivity as the detected signal is influenced not only by the optical absorption coefficient but also by other physical parameters of the sample
under observation like thermal expansion coefficient, specific heat and acoustic velocity. Also this method offers a higher degree of immunity from the scattering effect.
The PA effect is based on the sensitive detection of acoustic waves launched by the absorption of pulsed laser radiation by the sample under test via transient localized heating and subsequent expansion. For this, PA method uses a modulated narrow optical beam as an exciting energy. When the light hits the sample, some of the energy is absorbed by the molecules of sample resulting in a region of higher temperature. The rise in temperature will generate volumetric expansion, which will cause a pressure wave propagating away from the localized heat source. By adjusting the duty cycle of modulated signal, enough time can be provided for the sample to return to its original volume. If the optical energy is activated periodically then this expansion-contraction mechanism of the sample volume generates PA signal.
The US patent number US 5941821A entitled "Method and apparatus for noninvasive measurement of blood glucose by photoacoustics" discloses an apparatus based on the PA method. The block diagram of the patented invention is illustrated by Fig 1. This is a conventional photoacoustic measurement apparatus consisting of an excitation source 12, a lock-in amplifier 18, a modulator/controller 14, a processor 20 and a probe 16. The excitation source

12 generates a sound wave, which is transmitted to the human body through a transmitter and irradiated onto a biological tissue, such as skin. The probe 16 has a reference cell, a measurement cell, a window and a differential microphone. Finally the signal detected by probe 16 is transmitted to the lock-in amplifier. The processor 20 analyzes the frequencies of the signals extracted by the lock-in amplifier. Ultimately the conventional acoustic measurement apparatus determines the concentration of a target component based on this acoustic spectrum.
However, the acoustic signals are otherwise generated in the body by neurons or muscle cells that are always firing even when not specifically stimulated and also due to generation of natural vibrations caused by biological activities such as heartbeats. A major drawback of US 5941821A is that the interferences of such random noises that creep into the desired signal is not taken into account at all. Further, in this method acoustic wave is generated due to heat transfer of thin layer of irradiated tissue. But human body in normal condition also radiates heat which is highly dependent on physiological conditions of the patient. This is likely to introduce error. The cited patent does not take care of this factor as well.
US 6921366B2 entitled "Apparatus and method for non-invasively measuring bio-fluid concentrations using photoacoustic spectroscopy" teaches an apparatus that employs PA technique. Fig 2 shows the block diagram of this patented invention. As per this embodiment, the photoacoustic signal generated within the blood has to pass through subcutaneous fat, and tissue layers before being picked up by the acoustic transducer. This poses a serious limitation as the propagated acoustic signal characteristic would depend on thickness of the fat and tissue layer and hence would vary from individual to individual. The

invention seeks to control such variations in measurement of glucose levels, by assigning a compensation value N to compensate the tissue variation factor. However, the variations owing to the acoustic signals generated otherwise due to biological activities are not taken into account.
Therefore there is a need for an innovative and effective apparatus that could measure and monitor glucose level continuously in a noninvasive manner.
OBJECTS OF THE INVENTION
It is therefore an object of the invention is to propose a non-invasive apparatus for accurate measurement of the concentrations of body fluid components in particular blood glucose level, which eliminates the disadvantages of prior art.
Another object of the invention is to propose a non-invasive apparatus for accurate measurement of the concentrations of body fluid components in particular blood glucose level, which is capable of measuring the glucose levels at regular short intervals and even continuously,
Yet another object of the invention is to propose a non-invasive apparatus for accurate measurement of the concentrations of body fluid components in particular blood glucose level, which has a hand-held probe to be kept on the body part and hence easy to use.

Still another object of the invention is to propose a non-invasive apparatus for accurate measurement of the concentrations of body fluid components in particular blood glucose level, which can be adapted for on-line monitoring of blood glucose for the patients under intensive care.
A further object of the invention is to propose a non-invasive apparatus for accurate measurement of the concentrations of body fluid components in particular blood glucose level, which is easy to manufacture and cost-effective.
SUMMARY OF INVENTION
Accordingly, the present invention provides an apparatus for non-invasively measuring bio-fluid concentration comprising a light source for irradiating an incident light having predetermined wavelength band which can be absorbed into a target component of a living body on a predetermined part of a living body; an optical pulse generator circuit using which light source gives an optical pulse of optimum pulse width with proper repetition frequency; a transducer for detecbng the photoacoustic signal in a particular frequency band; and a signal processing block that recerves very low level signal which is amplified, Altered and digitally processed to remove noises and transformed to extract exact concentration of the target component in the human blood.
Tne apparatus further comprises a control unit to control the output optical power, a signal processing unit which consists of a front-end analog signal processing block including a digital processing block. The apparatus is enabled eliminate undesired noises coming due to noise and pressure change in human

body. The apparatus is provided with a spring loaded attachment to hold the finger In place. The probe has an Inbuilt transducer that can detect the acoustic signal, The light source, assisted by the pulse generator, produces a light beam of desired wavelength. The beam is allowed to fall upon a body part, normally finger. This results in generation of an acoustic signal within the body that propagates outwards. This propagated out coming acoustic signal amplitude is captured by the transducer that is kept below the body surface. The amplitude of this signal being a function of glucose concentration in the blood glucose, the glucose level is determined using the signal processing circuit. The signal processing unit has a built in chip embedded which compensates the effect of different sources of errors known to affect the signals. As the acoustic transducer that picks up the signal is in physical contact with the selected body part, the error due to variation of pressure exerted by the test site on to the transducer is compensated by suitable mechanical design of the housing.
In this method, the absorption of incident optical energy by the tissues and blood results in generation of acoustic signal within the body that propagates outward. The acoustic signal amplitude detected by a transducer at the body surface is a function of glucose concentration. But as the body experiences natural vibration due to constant cardiac and respiratory cycle or firing of neurons of muscle cells, which are of higher magnitude than the acoustic signal, so the detected acoustic signal representing blood glucose information is usually masked by the interfering signal from the body as well as other environmental and operating conditions. The glucose concentration information therefore is extracted from the photoacoustically generated signal using different signal processing logics, making the system insensitive to any change in subject dependent or any other sources of noise. Also the error due to varying pressure exerted by the subject

on to the transducer that is acoustically coupled to the body test site is eliminated by suitable mechanical design of the housing. Any variation in the desired information due to variation in either tissue character like melanin content of skin or variation in physiological conditions are suitably compensated.
BRIEF DESCRIPTION OF THE ACOMPANYING DRAWINGS
Fig. 1 shows a block diagram of a prior art apparatus for non-invasive measurement of blood glucose by photoacoustics.
Fig. 2 shows a block diagram of a prior art apparatus for non-invasively measuring bio-fluid concentrations using photoacoustic spectroscopy".
Fig. 3 shows a block diagram of a non-invasive bio-fluid concentration measuring system as per present invention.
Rg. 4 shows a block diagram of an optical pulse generator device used in the system of present invention.
Rg. 5 shows the interfacing of a transducer with the selected body part of a subject
Rg. 6 shows a spring loaded mechanical housing to ensure that the relative pressure variation between the test site and the transducer is negligible.

Rg. 7 depicts a flow chart for a first logic used for nullifying the effect of noises due to variation of pressure between the selected body part and the transducer, if any, and noise generated due to unwanted biological signals with respiratory and/or cardiac cycles,-skin/tissue characteristics etc.
Rg. 8 shows a second logic for extracting the desired information about the biological fluid from the decaying profile of the detected photoacoustic signal which is of damped oscillatory in nature.
Rg. 9 graphical representation on the variation of photoacoustic signal value for different glucose concentration in blood for a subject obtained using the first and the second logic of in Rg. 7 and Rg. 8.
Rg. 10 graphically shows correlation of signal value obtained using the first and second logics shown in Rg. 7 and Rg. 8 with a commercially available minimally invasive blood glucose meter.
DETAILED DESCRIPTION OF THE INVENTION
Rg. 3 shows the block diagram of an apparatus for non-invasive measurement of bio-fluid concentration according to an embodiment of the present invention. Referring to Rg. 3, an apparatus for non-invasively measuring bio-fluid concentration includes a light source 1. The light source (1) irradiates optical beam to human body 2, which is acoustically coupled with a transducer 4. Transducer signal is sent to signal processing block 3 for processing. As the light

Is illuminating a portion of body of the subject in pulsed nature to generate an acoustic signal, it is required to generate optical pulse with a desired pulse repetition frequency. Fig. 4 is the block diagram of optical pulse generator. An astable multivibrator 5 generates a square wave. The frequency of the wave is determined to achieve optimum signal to noise ratio. Then triggering a pulse generator 6 with the square wave generated in 5, electrical pulse is generated and taken into a driver 7 to drive a light source 1 to generate optical pulse.
In operation an optical pulse 1 with predetermined pulse width, repetition frequency and wavelength band, is applied to human body 2 on a predetermined portion of the human body. Normally the body part would be a finger. A targeted component of the human blood absorbs the incident optical energy. Here the target component of the human body 2 may represent a bio-fluid, such as glucose, hemoglobin etc. For different components the optical wavelength will be chosen accordingly. When the optical energy is absorbed by the predetermined part of the human body 2 a photoacoustic signal is generated as a consequence. The generated acoustic signal is sensed by the acoustically coupled transducer 4 whose resonance frequency is chosen according to the photoacoustic band. The signal obtained from the transducer 4, is processed using signal processing block 3.
Fig. 5 shows the placement of the finger with a first transducer (9). The first transducer 9 is placed below the finger (2) and ultrasound gel is used to couple' acoustic signal with the first transducer 9. Fig. 6 shows a spring loaded arrangement 8 for fixing the relative finger position with a second transducer 10 during the test. It is required because with little movement of human body, the pressure sensor will detect a pressure change giving a signal at output.

therefore the signal will change the original signal. But with this arrangement
the abovementioned problem can not be removed totally.
As the transducer senses pressure exerted on it so any pressure change due to hand movement of subject, gives an undesired signal at output. Beside this other human body noise also mixed with photoacoustic signal and remains in the same frequency band. These noises are coupled with random noises. To get rid of these problems a first logic as given in Fig 7 is used. In this logic, only op ca power dependent signal change is taken care. In Fig. 7 Ri is random noise which is removed in the averaging technique. HB is human body noise. This is independent of optical power applied on human body. PA1 and PA2 are PA signals at two different optical powers. So output S becomes independent of these noises.
Fig 8 shows a second logic used to extract the exact photoacoustic signal value from its decaying profile which is not constant for all subjects rather it changes with time even for a single subject. But to make the system subject independent it is indispensable to eliminate this effect. To do this the algorithm stated in Fig. 8 is used. Here the actual photoacoustic signal value PA is determined from ,ts decaying profile. To do so the received photoacoustic signal is transformed to a convenient domain. Here P (TR) is transformed photoacousbc signal. P (TR) contains actual signal value P and decaying factor D (TR). Then from transformed signal ft and ft are values of P (TR) at TR=TR1 and TR=TR2 respectively. Similarly D1 and D2 are decaying factors at TR1 and TR2 respectively. Then by division process relation between D1 and D2 is determined The result is given by K(TR) which is again function of TR. Then from the K (TR) value D1 is determined and from it PA value is extracted.

Fig. 9 shows the variation of extracted photoacoustic signal obtained using the first logic illustrated in Fig. 7 and Rg. 8, with time. In this experiment one subject drunk a glucose solution and examined the variation of signal value and

plotted against time. The variation is the same as the variation of glucose concentration in blood. In Fig. 9, the signal obtained using the first logic and the second logic stated in Fig. 7 and Fig. 8 is plotted against blood glucose concentration value obtained from commercially available invasive glucose meter. It shows same variation as of invasive meter. Therefore Fig. 9 and Fig. 10 show the potential of the algorithms used in the present invention.
The invention can be used to detect other biomolecules by changing the wavelength of the optical source. Wavelength has to be chosen according to the absorption spectra of the target component in the human body.
The apparatus would avoid taking out blood samples from the patients from time to time and could be very easy and convenient to uses. Such an apparatus would considerably improve the quality of life for diabetic patients, enhance the quality of health management, improve compliance for glucose monitoring and reduce complications and mortality associated with the disease.

WE CLAIM
1 A method for non-invasively measuring glucose concentration in blood comprising: irradiation of pulsed laser light beam of particular wavelength (900nm) falling
on finger tip;
wherein absorption of optical signals by glucose in the blood results in volumetric
expansion, and a photo acoustic signal generated during off period of the said
signal.
2. The method as claimed in claim 1, wherein the effect of noise signal nullified using an embedded signal processing device.
3. The method as claimed in claim 1, wherein the noise free photo acoustic signal displayed in embedded system.
4. The method as claimed in claim 3, wherein the features of displayed signal corresponds to the blood glucose level.