DESC:A SMARTPHONE BASED ORAL CANCER DETECTION DEVICE USING COMBINED TECHNIQUES OF FLUORESCENCE SPECTROSCOPY AND IMAGING
Field of Invention:
The present invention relates to the field of detection of oral cancer. The Invention particularly provides an efficient smartphone based oral cancer detection device based on integrated functioning of fluorescence spectroscopy and imaging.
Background of the Invention.
The following background discussion includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication expressly or implicitly referenced is prior art.
Globally, oral cancer is emerging as a major health issue, ranking as the second most prevalent cancer in India with 1.35 lakh new cases, and 0.75 lakh deaths reported by International Agency for Research on Cancer (IARC) in GLOBOCAN 2020. In India, high rate of growth of oral cancer incidences can be seen from the fact that 1.7 million cases are projected to be reported in 2035 as compared to 1million cases reported in 2012. High mortality shown by 5-year survival rate to be less than 45%, poses as a big challenge. In India, this is mainly attributed to late diagnosis, lack of effective diagnostic tools in rural areas and high prevalence of risk factors such as consumption of tobacco/pan masala. Early and effective diagnosis is needed to improve the present scenario of high morbidity and high mortality rates related to oral cancer.
Screening methods used for identifying oral cancer and pre-cancer stages are Conventional Oral Examination (COE), oral cytology, oral brush biopsy, staining (Toluidine Blue, Lugol’s Iodine, Methylene Blue) and light-based detection systems. The confirmatory diagnosis of oral cancer is tissue biopsy followed by histological examination. However, this procedure is invasive in nature and time consuming. Identifying the infected area is crucial to avoid unnecessary removal of normal regions. Hence, before biopsy, an effective and non-invasive screening technique is required. When tissue in the oral cavity is illuminated with UV-visible light, fluorescence occurs due to the various fluorophores naturally present in the epithelial lining and submucosa, the major ones being tryptophan, collagen, nicotinamide adenine dinucleotide (NADH), flavin adenine dinucleotide (FAD) and porphyrin. There are changes in the concentration of these fluorophores with progression of the disease. Fluorescence based optical techniques have the potential of early diagnosis of cancer since they are sensitive to subtle morphological and biochemical changes as the disease develops. Various optical techniques have been used in last several decades among which fluorescence spectroscopy and fluorescence imaging have independently emerged as most effective and widely explored by the researchers for early detection of various types of cancers. Both these techniques have high sensitivity and specificity, and are less time consuming. However, it seems very challenging when these bulky systems are transferred from lab to the clinics or for commercial use due to high cost and bulky size of different components. These days, with increase in the number of users, smartphone has become a suitable option to design portable and cost-effective systems. It is equipped with advanced technologies for imaging, sensing and networking, and can also be utilized for analysis purpose.
However, there is no integrated device that examines the oral abnormality, scans the infected area and performs point-based measurement of the area along with better wavelength resolution. There is also a need of a smart device for the detection of oral cancer which is robust, user-friendly and cost-effective.
Object(s) of the present invention:
The primary objective of the present invention is to overcome the drawback associated with prior art.
Another object of the present invention is to provide an efficient smartphone based oral cancer detection device based on integrated functioning of fluorescence spectroscopy and imaging.
Another object of the present invention is to provide an integrated device that examines the oral abnormality, scans the infected area and performs point-based measurement of the area along with better wavelength resolution.
Another object of the present invention is to provide a smart device for the detection of oral cancer which is robust, user-friendly and cost-effective.
Another object of the present invention is to provide a smartphone-based spectra-imaging device for oral cancer detection which has the ability to capture both spectra and image of an oral tissue on the same platform and is also able to analyze them further.
Summary of the invention:
In an aspect of the present invention there is provided a smartphone based oral cancer detection device based on fluorescence spectroscopy and imaging, comprising:

a) an imaging unit, wherein the imaging unit comprising:
a 405nm laser source with collimating lens (C),
a 70:30 beam splitter (BS) to illuminate the tissue sample with laser light and allow the resultant fluorescence image towards the mobile phone camera,
a 11 cm long cylindrical tube for easy access to the oral cavity and for the collection of maximum fluorescence at the detector end,
a 450nm long pass filter (LPF) to eliminate the source effect and
a smartphone to capture the output image in a RAW image format;

b) a spectroscopy unit, wherein the spectroscopy unit comprising two additional optical components other than the already existing components in the imaging unit: a collecting lens (CL) at the tip of the cylindrical tube for focussed light to be incident on the sample and a visible transmission grating to convert the emitted fluorescence signal into a spectral image and get recorded in the smartphone camera;

wherein the device is a bi-modal device, capturing the unprocessed FS and FI in RAW image format and analysing them further.
In an embodiment, the imaging unit scans an area of 10 mm (approx.).
In an embodiment, the spectroscopy unit records multiple spectra of the area scanned by the imaging module, with a resolution of 0.2658 nm/pixel.
In an embodiment, the device is able to capture fluorescence images (FI) and fluorescence spectra (FS) sequentially on a single platform with minimum changes in the overall geometry.
In an embodiment, FI and FS of some known fluorophores such as Flavin Adenine Dinucleotide (FAD) and Proto-porphyrin (PpIX), have been captured by the smartphone in .dng extension.
In an aspect of the present invention there is provided a method of operation of the device for capturing the fluorescence images (FI) and fluorescence spectra (FS) sequentially on a single platform with minimum changes in the overall geometry, comprising the steps of:
a) capturing the fluorescence spectra by a 1.2cm focal length collecting lens at the distal end and a visible transmission grating, parallel with the mobile phone camera;
b) capturing the raw image of the sample, wherein the fluorescence signal is coming from the grating arranged at 45 degrees and processing the captured raw images are in ADOBE READER PHOTOSHOP software and converting into a readable .tiff format which are further processed in MATLAB to generate the resultant fluorescence images and spectra.

This together with the other aspects of the present invention along with the various features of novelty that characterized the present disclosure is pointed out with particularity in claims annexed hereto and forms a part of the present invention. For better understanding of the present disclosure, its operating advantages, and the specified objective attained by its uses, reference should be made to the accompanying descriptive matter in which there are illustrated exemplary embodiments of the present invention.
Brief description of Drawings:
The accompanying drawings, which are incorporated in and constitute a part of this disclosure, illustrate exemplary embodiments and, together with the description, explain the disclosed principles. The reference numbers are used throughout the figures to describe the features and components. Some embodiments of system and/or methods in accordance with embodiments of the present subject matter are now described, by way of example only, and regarding the accompanying figures, in which
Figure 1: illustrates the photograph of the smartphone-based oral precancer detection device Figure 2: illustrates 3D design of holders for (a) laser source and various optical components, (b) smartphone and (c) device stand
Figure 3: illustrates 3D-CAD model of the smartphone-based oral precancer detection device
Figure 4: illustrates typical fluorescence spectra of (a) FAD and (b) porphyrin captured from the device
Figure 5: illustrates typical fluorescence images of (a) FAD and (b) porphyrin collected from the device
Figure 6: illustrates fluorescence spectra of FAD at different concentrations (0.003-0.500 mM)
Figure 7: illustrates fluorescence images of FAD at different concentrations (0.003-0.500 mM)
Figure 8: illustrates fluorescence spectra of buccal mucosa and inner lip captured from the device
Figure 9: illustrates fluorescence images of (a) buccal mucosa and (b) inner lip captured from the device
Detailed description of the invention:
In the present document, the word "exemplary" is used herein to mean "serving as an example, instance, or illustration." Any embodiment or implementation of the present subject matter described herein as "exemplary" is not necessarily to be construed as preferred or advantageous over other embodiments.
While the disclosure is susceptible to various modifications and alternative forms, specific embodiment thereof has been shown by way of example, in the drawings and will be described in detail below. It should be understood, however, that it is not intended to limit the disclosure to the specific forms disclosed, but on the contrary, the disclosure is to cover all modifications, equivalents, and alternative falling within the spirit and the scope of the disclosure.
The terms “comprises”, “comprising”, “includes”, or any other variations thereof, are intended to cover a non-exclusive inclusion, such that a setup, device or method that comprises a list of components or steps does not include only those components or steps but may include other components or steps not expressly listed or inherent to such setup or device or method. In other words, one or more elements in a system or apparatus proceeded by “comprises... a” does not, without more constraints, preclude the existence of other elements or additional elements in the system or method.
The invention provides an efficient smartphone based oral cancer detection device based on integrated functioning of fluorescence spectroscopy and imaging. The integrated device examines the oral abnormality, scans the infected area and performs point-based measurement of the area along with better wavelength resolution. The device is a smart device for the detection of oral cancer which is robust, user-friendly and cost-effective.
In an embodiment, the device is a smartphone-based spectra-imaging device for oral cancer detection which has the ability to capture both spectra and image of an oral tissue simultaneously and is also able to analyze them further. In another embodiment, the device is shown in figure 1.
In an aspect of the present invention there is provided a smartphone based oral cancer detection device based on fluorescence spectroscopy and imaging, comprising:

a) an imaging unit, wherein the imaging unit comprising:
a 405nm laser source with collimating lens (C),
a 70:30 beam splitter (BS) to illuminate the tissue sample with laser light and allow the resultant fluorescence image towards the mobile phone camera,
a 11 cm long cylindrical tube for easy access to the oral cavity and for the collection of maximum fluorescence at the detector end,
a 450nm long pass filter (LPF) to eliminate the source effect and
a smartphone to capture the output image in a RAW image format;

b) a spectroscopy unit, wherein the spectroscopy unit comprising two additional optical components other than the already existing components in the imaging unit: a collecting lens (CL) at the tip of the cylindrical tube for focussed light to be incident on the sample and a visible transmission grating to convert the emitted fluorescence signal into a spectral image and get recorded in the smartphone camera;

wherein the device is a bi-modal device, capturing the unprocessed FS and FI in RAW image format and analysing them further.
In an embodiment, the imaging unit scans an area of 10 mm (approx.).
In an embodiment, the spectroscopy unit records multiple spectra of the area scanned by the imaging module, with a resolution of 0.2658 nm/pixel.
In an embodiment, the device is able to capture fluorescence images (FI) and fluorescence spectra (FS) sequentially on a single platform with minimum changes in the overall geometry.
In an embodiment, FI and FS of some known fluorophores such as Flavin Adenine Dinucleotide (FAD) and Proto-porphyrin (PpIX), have been captured by the smartphone in .dng extension.
In an aspect of the present invention there is provided a method of operation of the device for capturing the fluorescence images (FI) and fluorescence spectra (FS) sequentially on a single platform with minimum changes in the overall geometry, comprising the steps of:
a) capturing the fluorescence images by keeping the entire optical assembly along with cylindrical tube fixed and perpendicular with the mobile phone camera;
b) while capturing the fluorescence spectra, a 1.2 cm focal length collecting lens and a visible transmission grating are also employed. An arrangement has been made to place the grating at 45 degrees, keeping the smartphone fixed, with fluorescence signal coming from the sample side.
c) all the captured raw images are then processed in ADOBE READER PHOTOSHOP software and converted into a readable .tiff format which are further processed in MATLAB to generate the resultant fluorescence images and spectra.
In an embodiment, the device comprises following components:
Imaging module: It consists of a 405nm laser source with collimating lens (C), a 70:30 beam splitter (BS) to illuminate the tissue sample with laser light and allow the resultant fluorescence image towards the mobile phone camera, a 7cm long cylindrical tube for easy access to the oral cavity and for the collection of maximum fluorescence at the detector end, a 450nm long pass filter (LPF) to eliminate the source effect and then a Redmi K20 smartphone to capture the output image in a RAW image format.
Spectroscopy module: This module consists of two additional optical components other than that already described in the imaging module: a collecting lens (CL) at the tip of the cylindrical tube for focussed light to be incident on the sample and a visible transmission grating to convert the emitted fluorescence signal into a spectral image and get recorded in the smartphone camera.
In an embodiment, the holders for various optical components, source and smartphone are being designed on a 3D CAD designing ZW3D software and printed through a 3D printing machine using a non-fluorescent and biodegradable PLA material. Figure 2 shows the detailed design of all the holders.
In an embodiment, Figure 3 shows an embodiment of the device. The device captures fluorescence images and spectra of some known fluorophores and oral tissue samples. For imaging, the smartphone camera is perpendicular to the optical path, While capturing the fluorescence spectra, a 1.2cm focal length collecting lens at the distal end and a visible transmission grating, parallel with the mobile phone camera, are also used for recording. An arrangement has also been made to place the grating and camera at 45 degrees, to the optical path, with fluorescent signal coming from the sample side. The captured raw spectral images are then processed in ADOBE READER PHOTOSHOP software and converted into a readable .tiff format which are further processed in MATLAB to generate the resultant fluorescent images and fluorescence spectra (shown in figure 3).
In an embodiment, Figure 4 shows the ability of the device in collecting the raw response of fluorescent dyes. Figure 5 represents the original recorded fluorescent images of FAD and porphyrin with their respective RGB bands. The images confirm that major component of FAD lies in the green band while porphyrin intensity in the red band. This device has the ability to capture both the spectra and images of different samples and provides satisfactory outcomes. FI and FS for different concentrations of FAD (0.003 – 0.500 milli-molar) have also been recorded to find out the limit of detection (LoD) of the device for both the modules. From figures 6 and 7, it shows that device can is able to detect concentrations as low as 0.007 mM.
In an embodiment, FI and FS have also been captured from buccal mucosa and inner lip of a normal human oral cavity with no symptoms and past history of oral diseases. Both the spectra, shown in figure 8, have major peaks around 520nm corresponding to the FAD fluorescence (a typical FS of FAD has been showcased in figure 4a). A small porphyrin peak is also visible in the case of buccal mucosa around 670 nm. Similarly, fluorescence images also have green band (around 520nm) intensity higher than the red band (around 630nm) in both the oral sites as demonstrated in figure 9.
In an embodiment, the fluorescence images and spectra (FI and FS) recorded from different oral cancer patients display an enhancement in the red band (porphyrin) as compared to those
from the normal volunteers. Porphyrin to FAD ratio (Iporphyrin/IFAD), referred to red to green ratio (Ired/Igreen) is taken as the diagnostic marker for classification among the groups.
Further, receiver operating characteristic analysis (ROC) is
employed on the intensity ratio values (Iporphyrin/IFAD). ROC is a
statistical method to check the performance of a test. In ROC analysis,
binary data sets among the various groups are classified by computing the
cut-off values. While applying ROC analysis in a diagnostic test, a two
dimensional curve is generated, known as ROC curve. It is a plot of
sensitivity and specificity. Sensitivity and specificity are the
probabilities of identifying unhealthy and healthy groups as positive and
negative respectively. Area under the ROC curve is also a parameter to
check the performance of a given diagnostic test. Sensitivity and
specificity are defined as
Sensitivity= ((True positive))/((True positive+False negative) )
Specificity= ((True negative))/((True negative+False positive) )

The device has following advantages:
A light weight, cost-effective and portable device which collects native fluorescence from oral tissue sample in the form spectra and images.
Both the fluorescence spectroscopy and imaging are performed on a single platform using mobile phone camera as detector.
Usage of miniaturized laser source along with several other optical components makes it more compact and user friendly.
Inclusion of a novel and unique methodology to calibrate the device and also to get the more accurate and reliable images.
Incorporation of smartphone for image collection, data analysis and display unit prove its applicability to be used as a standalone tool even in the remote areas.
The device is based on optical components of very small dimension which make it a very compact and easy to handle device.
Inclusion of smartphone in detection assembly replaces the commonly used bulky imaging and spectroscopic systems and data storage device.
The below table provides a comparison of device provided by the present invention with respect to the existing devices in terms of technical and financial features:
Specific features ViziLitePRO (Zila, Batesville, AR, USA) OralScan(Sascan
Meditech
Pvt. Ltd.) VELscope (LED Dental Inc., Vancouver, Canada) Identafi 3000 (DentalEZ, Bay Minette, AL, USA) Present invention
Size Small in size but requires external accessories Small screening tool attached with a data storage device Handheld, small in size but requires external accessories Small screening tool but requires external accessories Handheld and small in size with smartphone attached within the device
Technique Fluorescence
imaging Diffuse reflectance and fluorescence imaging Fluorescence
imaging Multispectral fluorescence and reflectance imaging Fluorescence imaging and spectroscopy combined
Handling Expertise requires to handle the device and interpret the screening outcomes Expertise requires to handle multiple accessories and interpret the screening outcomes Easy to handle but with a little bit experience Expertise requires to handle the device and interpret the screening outcomes Portable and easy to handle with a little bit experience
Cost Around 3 lakhs Around 5.9 lakhs Around 4.5 lakhs Around 2.25 lakhs Around 1 lakhs

,CLAIMS:We Claim:
1. A smartphone based oral cancer detection device based on the integrated fluorescence spectroscopy and imaging unit, comprising:

a) an imaging unit, wherein the imaging unit comprising:
i. a laser source, to be positioned in a Laser holder, with collimating lens (C),
ii. a beam splitter (BS) to illuminate the tissue sample with laser light and allow the resultant fluorescence image towards the mobile phone camera,
iii. approx. 11 cm long cylindrical tube, with disposable cap, for easy access to the oral cavity and for the collection of maximum fluorescence at the detector end,
iv. a 450nm long pass filter (LPF) to eliminate the source effect and
v. a smartphone to capture the output image in a RAW image format;

b) a spectroscopy unit, wherein the spectroscopy unit comprising two additional optical components, other than the already existing components in the imaging unit, comprising atleast a collecting lens (CL) at the tip of the cylindrical tube for focused light to be incident on the sample and a visible transmission grating to convert the emitted fluorescence signal into a spectral image and get recorded in the smartphone camera;

wherein the device is a bi-modal device, capturing the unprocessed FS and FI in RAW image format and analysing them further, for the detection of cancer.
2. The device as claimed in claim 1, wherein the smartphone camera is positioned perpendicular to the optical path for imaging.
3. The device as claimed in claim 1, wherein while capturing the fluorescence spectra, a 1.2cm focal length collecting lens at the distal end and a visible transmission grating, parallel with the mobile phone camera, are positioned for recording, wherein the grating and camera are positioned at 45 degrees, to the optical path, with fluorescent signal coming from the sample side.
4. The device as claimed in claim 1, wherein device can is able to detect concentrations as low as 0.007 mM.
5. The device as claimed in claim 1, wherein the imaging unit scans an area of 10 mm (approx.).
6. The device as claimed in claim 1, wherein the spectroscopy unit records multiple spectra of the area scanned by the imaging module, with a resolution of 0.2658 nm/pixel.
7. The device as claimed in claim 1, wherein the device is able to capture fluorescence images (FI) and fluorescence spectra (FS) sequentially on a single platform with minimum changes in the overall geometry.
8. The device as claimed in claim 1, wherein FI and FS of fluorophores comprising Flavin Adenine Dinucleotide (FAD) and Proto-porphyrin (PpIX), have been captured by the smartphone in .dng extension.
9. A method of operation of the device as claimed in claim 1, for capturing the fluorescence images (FI) and fluorescence spectra (FS) sequentially on a single platform with minimum changes in the overall geometry, comprising the steps of:
a) capturing the fluorescence images by keeping the entire optical assembly along with cylindrical tube fixed and perpendicular with the mobile phone camera;
b) while capturing the fluorescence spectra, a 1.2 cm focal length collecting lens and a visible transmission grating are also employed. An arrangement has been made to place the grating at 45 degrees, keeping the smartphone fixed, with fluorescence signal coming from the sample side.
c) all the captured raw images are then processed in ADOBE READER PHOTOSHOP software and converted into a readable .tiff format which are further processed in MATLAB to generate the resultant fluorescence images and spectra.