FIELD OF INVENTION

[001] The present invention relates to a low cost and portable diffuse reflectance spectral ratio based optical biopsy system for clinical diagnostics. This particularly relates to a non-invasive optical diagnostic system to identify tissue abnormalities in skin  oral cavity  cervix  prostate  lungs  gastro-intestine  urinary bladder  prostate  colon etc.

BACKGROUND OF INVENTION
[002] Spectroscopic analysis is generally considered as a simple  non-invasive tool to study the morphological properties of tissues since the optical spectral characteristics carry crucial information about its properties. Spectroscopic techniques can also be used to reveal key tissue features like cellular metabolic rate  intravascular oxygenation etc. A number of spectroscopic approaches such as diffuse reflectance spectroscopy  florescence spectroscopy and Raman spectroscopy have been reported for optical biopsy applications. Among these  diffuse reflectance spectroscopy is one of the simplest and cost effective methods for understanding biological tissue characteristics. Such methods can be used where standard excisional biopsy is hazardous or unadvisable.
[003] Diffuse Reflectance Spectroscopic technique involves detection and analysis of a portion of the incident light that under goes multiple elastic scattering owing to in-homogeneities in the refractive index of the tissue. Recent results have shown that tissue back scattering is altered as the size of the nucleus increases and the nuclear texture becomes coarser. The potential for using diffuse reflectance spectroscopic techniques is higher because elastic interactions are much stronger than inelastic interactions.
[004] Diffuse reflectance measurement system reported till now  employs a broadband light source such as tungsten halogen lamp and a Spectrophotometer as shown in Figure 1. The system uses a fiber probe  with multiple fibers as shown in Figure 2  for delivering light to the sample under investigation and to collect the diffuse reflected light back to the spectrophotometer. These equipments are bulky and expensive and hence can be used only in laboratories. Moreover such bulky solutions are not suited for upcoming point of care diagnostics for masses.

OBJECT OF INVENTION
[005] The main objective of the present invention is to provide a portable and low cost diffuse reflectance measurement system for biological tissue characterization and hence for diagnostic purpose. The system employs simple LEDs and PIN photo-detectors instead of bulky sources and costly spectrophotometers. The LEDs and photo detectors are selected based on the design calculations on central wavelength  spectral width  power and sensitivity. A time division multiplexed approach is developed to use individual LED sources at specific wavelengths and a single photodiode.
[006] A specific objective of the invention is to provide a portable and low cost cancer detection device for skin  oral cavity  cervix  prostate  colon etc. In another words  this provides a low cost solution for point of care ‘optical biopsy’ based on diffuse reflectance.
[007] Another objective of the present invention is to improve the performance of the diffuse reflectance measurement through techniques such as source modulation  referencing and averaging techniques.
[008] These and other aspects of the embodiments herein will be better appreciated and understood when considered in conjunction with the following description and the accompanying drawings. It should be understood  however  that the following descriptions  while indicating preferred embodiments and numerous specific details thereof  are given by way of illustration and not of limitation. Many changes and modifications may be made within the scope of the embodiments herein without departing from the spirit thereof  and the embodiments herein include all such modifications.

STATEMENT OF INVENTION
[009] The embodiments herein achieve a portable and cost effective diffuse reflectance spectral ratio based optical biopsy equipment  that employs multiple LED sources or a single white LED in combination with multiple or single PIN photodiode in a time multiplexed configuration for diagnosis of tissue abnormalities; wherein the system compares the differential spectral characteristics at multiple wavelengths to predict the tissue characteristics.
[0010] Referring now to the drawings  and more particularly to FIGS. 1 through 11  where similar reference characters denote corresponding features consistently throughout the figures  there are shown preferred embodiments.

BRIEF DESCRIPTION OF FIGURES
[0011] This invention is illustrated in the accompanying drawings  throughout which like reference letters indicate corresponding parts in the various figures. The embodiments herein will be better understood from the following description with reference to the drawings  in which:
[0012] Figure 1 depicts the laboratory model of a Reported Diffuse Reflectance Spectroscopic System;
[0013] Figure 2 depicts the structure of the fiber probe for diffuse reflectance measurement;
[0014] Figure 3 depicts a system architecture employing multiple LEDs and PIN photo-diodes  according to embodiments as disclosed herein;
[0015] Figure 4 depicts the optical schematics of the Optical Engine  according to embodiments as disclosed herein;
[0016] Figure 5 depicts a Generated multi-peak spectral profile  according to embodiments as disclosed herein;
[0017] Figure 6 depicts an Opto-mechanical assembly of Optical Engine  according to embodiments as disclosed herein;
[0018] Figure 7 depicts a system architecture employing a white light LED and a single PIN diode  according to embodiments as disclosed herein;
[0019] Figure 8 depicts a System Architecture employing an optical switch to combine light  according to embodiments as disclosed herein;
[0020] Figure 9 depicts a Block Diagram of the high sensitivity-detection circuit  according to embodiments as disclosed herein;
[0021] Figure 10 depicts a Mounting of Optical Engine on a PCB consisting of the high sensitive photo-detection circuit and processing unit  according to embodiments as disclosed herein; and
[0022] Figure 11 depicts a Mobile application based diffuse reflectance measurement system  according to embodiments as disclosed herein.

DETAILED DESCRIPTION OF INVENTION
[0023] The embodiments herein and the various features and advantageous details thereof are explained more fully with reference to the non-limiting embodiments that are illustrated in the accompanying drawings and detailed in the following description. Descriptions of well-known components and processing techniques are omitted so as to not unnecessarily obscure the embodiments herein. The examples used herein are intended merely to facilitate an understanding of ways in which the embodiments herein may be practiced and to further enable those of skill in the art to practice the embodiments herein. Accordingly  the examples should not be construed as limiting the scope of the embodiments herein.
[0024] The schematic of Diffuse Reflectance Spectral Ratio Measurement System is shown in Figure 3. The system comprises of:
- An “Optical Engine” with two or more LEDs at specific wavelengths with optics to combine these light and two or more PIN photo-detectors with optics to de-multiplex diffuse reflected wavelengths
- A multi-fiber Diffuse Reflectance Excitation and Collection Fiber Probe
- High Sensitivity Optical Detection System along with Data Acquisition and Control Module  Power Management Module and a Graphical User Interface
[0025] Light Emitting Diodes (LED) is used as excitation source owing to the compact size and low power consumption. For Diffuse Reflectance spectral characterization  an excitation spectrum with multiple spectral peaks may be required; the required spectral profile can be generated by combining light from multiple LEDs. In one such application for oral cancer detection  the required wavelengths are 545nm and 575nm with a spectral width of 10nm. The optical schematic of low cost optical engine is shown in Figure 4. The transmitter section of the optical engine assembly consists of LEDs  collimating lenses  dichroic mirror  focussing lenses and fiber adaptor. The generated excitation profile with multiple peaks is shown in Figure 5. The receiver path of the optical engine assembly  used to de-multiplex the different spectral components  consists of collimating lenses  dichroic filter  focussing lenses and PIN photo diodes as shown in Figure 4. In addition to the elements shown  suitable band pass filters can be used before the photo-diodes to improve the spectral isolation. The optical engine is assembled on precision mechanical rail like structure as shown in Figure 6  and is the Optical Engine. This optical engine is designed with half open structure  so that the elements can be assembled from the top. The precision of the mechanical structure ensures proper alignment between various optical elements  thus supporting passive alignment and hence fast assembly.
[0026] The power from LEDs is combined using dichroic combiners or using an all-fiber combiner. Typically LEDs with a fiber coupled power of 0.5mW is preferred. It is also possible to use a single white light LED instead of using multiple LEDs; in that case we can eliminate the multiplexing optics as shown in Figure 7. The typical power requirement of white LEDs are of the order of several W  to get required spectral power component. In another embodiment  the multiplexing optics can be eliminated using an optical switch as shown in Figure 8.
[0027] A stable LED drive circuit is required. These sources can be operated either in CW mode or pulsed mode. The pulse mode operation helps in improving the signal to noise ratio  by eliminating any ambient light that gets into the system. Different light sources can be modulated at different frequencies to further improve the isolation between different spectral components during the detection process.
[0028] The LEDs can be excited on a time division multiplexed manner so that a single photo-detector is required for detection.
[0029] Flexible and well designed fiber optic probes are required for carrying the excitation light to the sample and to collect the diffuse reflected light back from the sample to the detection unit. The probe is designed for the transmission of diffuse reflected light that supports the required spectral range. The efficiency of the probe depends on the fiber geometry arrangement and the polishing quality at the fiber tip. The fiber is selected in such a way that it has low attenuation in the required spectral band and has sufficient numerical aperture to cover the area under inspection. The excitation and collection fibers need not be the same. The excitation fiber is silica based with a diameter of 100µm or 400 µm  while the pickup fiber is having a diameter of 400 µm. The geometrical positioning of the fiber will be based in such a way that it has maximum collection efficiency. The probe is sterilize-able. This probe can be further enhanced to provide suitable lighting and direct image capturing provisions. Options for controlling the data capture and small display can also be integrated in the probe for easy operation and to make it ultra compact.
[0030] The Si-PIN detector leads from Optical engine are mounted directly on the Printed Circuit Board. The schematic of the high sensitivity synchronous detection circuit is shown in Figure 9. The output from the photodiode is amplified by a logarithmic Trans-impedance stage. In lock-in amplifier  a reference signal at known frequency is used to pulse the excitation source and the output signal is measured at the excitation frequency this eliminates majority of the noise from the measured signal. The data acquisition and control circuit consists of a micro-controller  DAC/ADC for analog/digital signal conversion and a Bluetooth module for communication with GUI. This circuit controls all aspects of the device operation. The circuit accepts the inputs (measurement settings) from the client  via USB interface. This section controls the LED power by sending set point voltages to the LED drive circuit. The circuit also reads the optical data (output of lock-in amplifier circuit) from both channels and analyze the data and stores it. The device is powered by a battery pack and external power supply. The power to the circuit is multiplexed between the battery and the dc adapter. When the adapter is connected it powers the circuits and charges the battery. This is achieved using a battery charger IC and a combination of diodes  so that there is a seamless transition between the two power sources. The Printed Circuit Board with all these functions is shown in Figure 10. The optical engine is connected directly to the PCB.
[0031] Before starting the measurement pre-registration of the diffuse reflected LED power  using a standard reflector  is done at the processor. This value is used to extract the exact amount of diffuse reflectance happening at the tissue under investigation. Since the diffuse reflected spectral power of individual LEDs are registered at the processor  before stating the measurement  LEDs with different fiber coupled power can be used in the system.
The tissue is exposed to light and the diffuse reflected spectral power is recorded at the processor again. This power is compared with the reference value and the differential spectral reflectance is estimated. This differential spectral reflectance gives an indication of the health of the tissue. Based on the value  the tissue can be graded as normal  pre-malignant or malignant.
[0032] The processing and display part can be implemented on a standard mobile platform as shown in Figure 11. This helps doctors to view the results in a graphical mode. This also allows the clinicians and doctors to save the results for future reference. There is a configuration mode  through which the settings of the device can be configured.
[0033] Even though the system described here is for tissue classification  the application of the system is not limited to medical field  but can be used in other industries like chemical  food industries etc.
[0034] Embodiments herein disclose a diffuse reflectance based optical biopsy equipment having LED at different wavelengths as excitation sources  where dichroic filters are used to combine different wavelengths  to generate a characteristic light with desired spectral content.
[0035] Disclosed herein is a diffuse reflectance measurement system having PIN photodiodes for electrical to Optical conversion  the diffuse reflected light is de-multiplexed using dichroic filters before giving to photodiodes
[0036] Disclosed herein is also using a single LED with the above disclosed systems  instead of multiple LEDs
[0037] Disclosed herein is also multiplexing of light from different LEDs in the above mentioned systems using an all-fiber method.
[0038] Disclosed herein is multiplexing of light from different LEDs implemented using an optical switch and the detection using a single PIN diode in the above mentioned systems.
[0039] Disclosed herein is operation of the different LEDs in a time division multiplexed manner to eliminate the need for multiple photo-diodes in the above mentioned systems.
[0040] Disclosed herein is employment of an optical engine designed in half open structure to facilitate easy alignment of components and stability to the above mentioned systems.
[0041] Also  disclosed herein is modulating the source to avoid the effect of ambient light  rather than using a continuous wave source. This modulation can also be used to avoid the requirement of multiple photo detectors.
[0042] Disclosed herein is also pre-recoding of the spectral power contents to take care of the different optical powers generated by the LEDs  thus not necessitating the requirement of equal power sources for the instrument.
[0043] Disclosed herein is classification of the biological tissues based on the diffuse reflectance absorption spectral ratio and displaying the results.
[0044] Systems disclosed herein can be used in cancer screening systems such as oral  cervical  breast  prostate  skin etc.
[0045] Systems disclosed herein can be used in combination with a mobile phone or similar gadgets for processing and display.
[0046] The foregoing description of the specific embodiments will so fully reveal the general nature of the embodiments herein that others can  by applying current knowledge  readily modify and/or adapt for various applications such specific embodiments without departing from the generic concept  and  therefore  such adaptations and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments. It is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation. Therefore  while the embodiments herein have been described in terms of preferred embodiments  those skilled in the art will recognize that the embodiments herein can be practiced with modification within the spirit and scope of the embodiments as described herein.

Dated: 2nd day of November Dr Kalyan Chakravarthy

ABSTRACT
Portable and cost-effective diffuse reflectance based optical biopsy system for clinical diagnostics. The present invention relates to a low cost and portable diffuse reflectance spectral ratio based optical biopsy system for clinical diagnostics. This particularly relates to a non-invasive optical diagnostic system to identify tissue abnormalities in skin  oral cavity  cervix  prostate  lungs  gastro-intestine  urinary bladder  prostate  colon etc. Most of the diffuse reflectance spectral analysis can be concluded analyzing those specific wavelengths  where the exact information is embedded. All other data available at other wavelengths do not contribute to any diagnostics in this specific case. This eliminates the need for a costly spectrophotometer as well as bulky sources for point-of-care diagnostics.