FIELD OF INVENTION
[001] This invention relates to a low cost and portable diffuse reflectance spectral ratio based optical biopsy system for clinical diagnostics, and more particularly to a non-invasive optical diagnostic system for real time and in-vivo monitoring of pre-malignant lesions in oral cavity, cervix, oesophagus, prostate, lungs, gastro-intestine, urinary bladder and colon and a portable, smart biopsy system for in-vivo epithelial cancer screening
BACKGROUND OF INVENTION
[002] Optical spectroscopic techniques provide non-invasive and real-time information sensitive to the biochemical and morphological properties of tissues like cellular metabolic rate, vascularity, intravascular oxygenation thereby to precisely locate neoplastic mucosal changes. Emerging new generation spectroscopic techniques like Raman, diffuse reflectance, auto-fluorescence are the promising modalities for optical biopsy applications. Among them, diffuse reflectance is the simplest and cost effective modality for early diagnosis of tissue malignancy. Such methods can perform as smart biopsy tool for large human population.
[003] Diffuse reflectance technique involves detection and analysis of the spectral regions of interest in the diffuse reflected light from an illuminated tissue under in-vivo examination. Spectral regions of interest involve the oxygenated hemoglobin absorption of visible light band. The

decrease in diffuse reflectance intensity of abnormal mucosa due to increased absorption at the thickened epithelium and local architectural changes at the cellular and sub-cellular levels, neo-vascularization etc. affects the elastic scattering properties of the tissue. As elastic interactions are much stronger, the potential of this technique is higher to discriminate between malignant and normal epithelial tissues.
[004] Diffuse reflectance measurement system reported till now employs a broadband white light source such as tungsten halogen lamp and a spectrometer (as shown in Figure 1). The system uses a fiber optic probe with multiple fibers (as shown in Figure 1), for light delivery towards the sample under investigation and to capture the diffuse reflected light back to the spectrometer. These bulky, expensive equipment are limited to laboratories thereby cannot effectively assist medical practitioners and hence not a viable solution for en masse diagnostics. OBJECT OF INVENTION
[005] The principal object of this invention is to propose a portable, low cost, diffuse reflectance based optical biopsy system. This system employs LED (Light Emitting Diode) sources, optical filters, aspheric lenses and PIN (Positive Intrinsic Negative) photo-detectors instead of bulky light sources and spectrometers, wherein the LEDs photodiodes, optical filters, lenses are selected based on the design calculations on central wavelength, spectral width, optical power and sensitivity.

[006] Another object of this invention is to provide a non-invasive optical biopsy system for real time and in-vivo monitoring of pre-malignant lesions in oral cavity, cervix, oesophagus, prostate, lungs, gastro-intestine, urinary bladder and colon.
STATEMENT OF INVENTION
[007] Accordingly the invention provides an apparatus comprising of a transmitter optical engine with an LED source having visible light spectrum, a novel fiber-optic probe to transport light towards the tissue and back, a receiver optical engine for de-multiplexing wavelengths which is characterized in that to provide precise optical alignments, a high sensitivity detection and amplification circuit to digitize the measurement values.
[008] There is also provided a method of combination with another device, wherein another device may be at least one of a mobile phone, tablet or computer with a Graphical User Interface (GUI) for processing and displaying the real-time results during examination.
[009] The novel fiber optic probe comprises of fibers equally spaced around a central, single optical fiber in such a way to eliminate the collection of specular reflected light.
[0010] 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.
BRIEF DESCRIPTION OF FIGURES
[0011] This invention is illustrated in the accompanying drawings, through out 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] Fig-1 depicts an optical biopsy system based on diffuse reflectance spectroscopic system for clinical diagnostics existing in prior art;
[0013] Fig-2 depicts the present invention of diffuse reflectance based portable optical biopsy device according to the embodiments as disclosed herein;
[0014] Fig-3 depicts block schematics of high sensitivity detection circuit according to the embodiments as disclosed herein;
[0015] Fig-4 depicts the optical schematics of transmitter optical engine, according to the embodiments as disclosed herein;

[0016] Fig-5 depicts the generated spectral profile for diffuse reflectance excitation, according to the embodiments as disclosed herein;
[0017] Fig-6 depicts the Optical schematics of de-multiplexing and thereby focusing of isolated spectral regions of interest towards photodiodes, according to the embodiments as disclosed herein;
[0018] Fig-7 depicts receiver optical engine, according to the embodiments as disclosed herein;
[0019] Fig-8 depicts the generated spectral profile of 577nm band focused on photodiode, according to the embodiments as disclosed herein;
[0020] Fig-9 depicts the generated spectral profile of 540nm band focused on photodiode, according to the embodiments as disclosed herein;
[0021] Fig-10 depicts algorithm for diffuse reflectance spectral ratio calculation, according to the embodiments as disclosed herein;
[0022] Fig-11 depicts the perspective view of fiber optic probe for diffuse reflectance measurement system, according to the embodiments as disclosed herein;
[0023] Fig-12 depicts the cross-sectional view of fiber position geometry inside the novel diffuse reflectance probe, according to the embodiments as disclosed herein;
[0024] Fig-13 depicts the cross-sectional view of illumination and collection geometry for tiny fibers, according to the embodiments as disclosed herein;

[0025] Fig-14 depicts the structure of bend probe for accessing inner oral areas, according to the embodiments as disclosed herein; and
[0026] Fig-15 demonstrates the formation of separation between illumination & collection fibers for elimination of specular reflection, according to the embodiments as disclosed herein.

DETAILED DESCRIPTION OF INVENTION
[0027] 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.
[0028] Shown in Fig-2 is the diffuse reflectance point care optical biopsy system generally indicated at 20, which embodies several aspects of the present invention. The system generally has a housing assembly 23, which contains a transmitter optical engine (32 in Fig-3) having a LED source, a receiver optical engine (37 in Fig-3) to de-multiplex diffuse reflected wavelengths and a high sensitivity detection and amplification circuit, control module are embedded in the printed circuit board (31 in Fig-3) to digitize the measurement values and transmit them wirelessly through Bluetooth module (36 in Fig-3). The digitized values transmitted are acquired through the serial port of the personal computer 27 or a tablet device 28. The tissue 26 to be diagnosed optically is kept in contact through

a detachable, bifurcated diffuse reflectance fiber probe 24 having a light transporting arm 40, connected to transmitter optical engine and a light collection arm 39, connected to receiver optical engine. For one application like Oral cancer detection, fiber probe is placed over the tissue ensuring normal light incidence during the diagnostic procedure. For each patient scan, medical grade, transparent, disposable sleeve 25 is used. The switched mode power supply 21 energizes the system through an electrical cord 19.
[0029] As shown in Fig-2, 27&28 are Laptop or personal computer and Tablet/palm-let type devices respectively for receiving the digitized values of measurement. These devices contain Graphical User Interface (GUI) for processing and displaying the real-time results during examination. This also helps clinicians and medical practitioners to save the results for future reference. There is a configuration mode through which the settings of the measurements can be configured.
[0030] As shown in Fig-4, transmitter optical engine contains diffuse reflectance excitation LED source positioned such that couple light directly into the illumination fiber of diffuse reflectance probe 24 which will be described later. The Excitation LED source 51 may have an output power of lOOmW emits wavelengths in the Green-Yellow band of light spectrum (see Fig-5). However other known white light sources having wavelengths in this band like halogen source also can be used.

[0031] Fig-6 illustrates the functional schematic of receiver optical engine. Diffuse reflected light received from collection arm 39 of fiber probe is collimated by coated aspheric lens 55 and hence de-multiplexed by dichroic long pass filter 56 into a reflected beam 66 of wavelength range 400-555nm and a transmitted beam 65 of wavelength range 565-750nm.Other wavelength ranges for reflected & transmitted beams corresponding to the spectral band to be measured are also under the scope of the present invention. The reflected beam 66 is filtered by an optical band pass filter 60, having a pass band of lOnm width and central wavelength of 540nm. Filtered beam is focused to the PIN photo-diode 62, by an aspheric lens 61. As described above, transmitted beam 65 is filtered by an optical band pass filter having lOnm width around 577nm central wavelength and then focused to PIN photo-diode 59 using an aspheric lens 58. Hence the photodiode 62 produces a photocurrent corresponding to light intensity at 540nm with lOnm bandwidth and photodiode 59 produces a photocurrent corresponding to light intensity at 577nm with lOnm bandwidth.
[0032] As best shown in Fig-7, optical elements are precisely positioned inside mechanical housing 70, which ensures proper alignment and whole structure is known as receiver optical engine. The precision of mechanical housing and threaded mounts 72 ensures passive alignments of lenses inside the engine. The threaded lock-rings 73 allow active alignment

of PIN photodiodes 62, 59 and rotatable mount 74 allows active alignment of dichroic filter 56. PIN photodiodes 62, 59 are electrically isolated by Teflon connector mount 75. The receiver engine can be any shape or size which is also under the scope of this invention.
[0033] As specified earlier, transmitter engine 32 and receiver engine 37 are carried inside the housing assembly 23 whose functional schematic as shown in Fig-3. Also within housing assembly 41 is the layout of circuit board comprising tans-impedance amplifiers 34, 44 for converting photodiode currents (usually in nano-amperes) into different voltage levels, a controller 35 that controls the operation of whole electronic circuit, a driver circuit 33 for excitation LED source and a Bluetooth module 36 for transmitting digitized values of individual photocurrent corresponding to the two wavelength bands. The controller can be any type of processor which includes embedded firmware for control logic.
[0034] Fig-10 describes the algorithm for calculation of diffuse reflectance spectral ratio. The digitized values received through the Bluetooth are converted to voltage levels for each photodiode channels. These voltage levels are converted to photocurrents signals corresponding to each photodiodes and filtering performed. Optical powers at each photodiodes are determined from its sensitivity. Using the efficiency measured for each de-multiplexed channels, diffuse reflected powers at

each wavelength band is calculated and ratio of the same determines the spectral ratio.
[0035] Fig-11 shows the conventional, flexible and elongated fiber optic probe for diffuse reflectance measurement which includes a few fibers closely positioned around a single optical fiber as described in cross-sectional view Fig-12. The inventers determined central fiber 94 for the delivery of excitation light towards the tissue and surrounding fibers 93 for collection of diffuse reflected light back to the receiver optical engine. The inventors also determined the fibers must have a low attenuation in the required spectral range and sufficient numerical aperture to illuminate the area under inspection. Other than conventional fiber probes, the present invention includes a spacing 91 between illumination 94 and collection 93 fibers to negate specular reflection inside the collection fibers which will be discussed later. Any such configuration of radial spacing between illumination and collection fibers is also under the scope of the present invention.
[0036] Referring more particularly to Fig-12, the invention is not limited to a single optical fiber and surrounding eight fibers but the configuration can be extended for many fibers constituting illumination and collection fibers separately. Fig-13 depicts another embodiment of fiber probe, as the cross-section shows an annular area 103 comprises several tiny optical fibers which deliver light towards tissue and tiny optical fibers

inside the annular area 102 collects diffuse reflected light back to the receiver optical engine. Here the spacing 105 avoids specular reflection entering into the collection fibers.
[0037] For one application like Oral cancer screening, straight end 29 of metallic part can access only proximal areas inside mouth. Shown in Fig-14 is the bend probe for accessing inner oral areas inside the mouth. Bending provides normal light incidence over tissues and hence can sufficiently collect diffuse reflected light.
[0038] Fig-15 depicts the side view of diffuse reflectance collection geometry inside the present invention of fiber probe. Fig-15 describes all the fibers with same numerical aperture inside the probe. However the scope of present invention includes separate numerical aperture for light excitation and collection of diffuse reflected light. The illumination fiber delivers a cone of light 30 having numerical aperture 111 towards the tissue 26. The specular reflected light rays 112 from the surface of tissue also have angle of reflection 111 same as that of numerical aperture. For a separation 110 between fibers 93 & 94, specular reflected light rays 112 do not couple inside the collection fibers. This separation is in direct proportion to the distance 110 and numerical aperture 111 of optical fibers.
[0039] Notwithstanding the detailed illustration of invention is based on present best practical and preferred embodiments, it is to be understood that the invention is not only limited to disclosed embodiments

but also cover the equivalent modifications and changes that are within the scope and intentions of claims appended. The features of any of these embodiments may be used with another in a way that will now be understood from the foregoing disclosure. It is to be understood that the terminologies employed herein are for the purpose of illustration and not of the limitation.
[0040] 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.

STATEMENT OF CLAIMS
We claim:
1. An optical biopsy equipment based on diffuse reflectance spectral ratio
for performing biopsy of a tissue, the equipment comprising
an optical transmitter engine for generating a light using a LED (Light Emitting Diode) source with desired spectrum for diffuse reflectance excitation;
a fiber optic probe for carrying the generated light towards the tissue and for transmitting diffused reflected light back to a detection unit; and
a compact receiver optical engine to de-multiplex wavelengths bands of the diffused reflected light and perform optical to electrical conversion of the de-multiplexed wavelength bands using photodiodes.
2. The optical biopsy equipment as claimed in claim 1, wherein the equipment differentiates neoplastic changes in tissues based on diffuse reflectance absorption spectral ratio and displaying the results insitu.
3. The optical biopsy equipment as claimed in claim 1, wherein a LED and excitation fiber is positioned inside the optical transmitter engine.
4. The optical biopsy equipment as claimed in claim 1, wherein the Aspheric lenses, Dichroic filters, Optical band-pass filters and Photodiodes are precisely positioned inside the optical transmitter engine for Optical alignment.

5. The optical biopsy equipment as claimed in claim 1, wherein the fiber optic probe comprises of fibers equally spaced around a central, single optical fiber in such a way to eliminate the collection of specular reflected light.
6. The optical biopsy equipment as claimed in claim 1, wherein the equipment is used in combination with another device, wherein another device may be at least one of a mobile phone, tablet or computer.