WO2019202410A1

WO2019202410A1 - Non invasive point of care diagnostics for sickle cell disease

Info

Publication number: WO2019202410A1
Application number: PCT/IB2019/050846
Authority: WO
Inventors: Ayepalayam Ramaswamy POONGOTHAI; Meka VENKATESWARA; Vegulada DURGA RAO
Original assignee: Chrogene Aarogyam Biotech Private Limited
Priority date: 2018-04-18
Filing date: 2019-02-03
Publication date: 2019-10-24

Abstract

The portable device is a non-invasive and battery operated detection device that identifies sickle cell disease in the human finger tissue. The device comprises a multi wavelength radiating means, a photo detecting means, a wavelength selector, a magnetic means, a pre-amplifier, a sampling and holding means, an amplifying and filtering means, a controlling means and a display. The multi-wavelength radiating means is configured to emit a light beam on the human finger tissue with a selected wavelength. The photo detecting means placed below the tissue to detect the absorbance of the light beam. The electromagnetic ring is configured to apply a magnetic field through the tissue. The controlling means is configured to control the light wavelength and the magnetic field excitation. The controlling means is incorporated with specially algorithm that receives the photo detecting means output and processes the data to obtain parameters to identify the sickle cell disease.

Description

NON INVASIVE POINT OF CARE DIAGNOSTICS FOR SICKLE CELL DISEASE DESCRIPTION

Field of Invention:

[0001] The present invention relates in general to the non-invasive diagnostics for sickle cell disease. More specifically, the invention relates to a non-invasive portable device and method that utilizes a specially designed algorithm to identify the sickle cell disease based on different wavelength absorbance responses from the human finger tissue.

Background of the invention:

[0002] Sickle-cell disease (SCD) is a group of blood disorders typically inherited from person's parents. Sickle cell disease may occur from the birth stage itself, but disease symptoms cannot be observed in most of the infants until they are few months old. Symptoms of the sickle cell disease are not similar for everyone. In some people, they are mild and in others they are severe and require hospitalization. Millions of people are affected by SCD worldwide such as sub-saharan Africa, central India, and eastern Brazil. Every year, six million children are born with SCD or sickle cell trait. Up to 90% of the newborns with SCD die soon after their birth from this disease, if undiagnosed.

[0003] Sickle-cell disease occurs when a person inherits two abnormal copies of the haemoglobin gene, one from each parent. SCD is one of the most common inherited blood disorders in the world. SCD is caused by the inheritance of two copies of the gene encoding hemoglobin S, a protein that results from a missense mutation in the b-globin sub unit of hemoglobin A.

[0004] In sickle cell disease, inherited group of disorders, red blood cells contort into a sickle shape. The cells die early, leaving a shortage of healthy red blood cells which is referred as sickle cell anemia and the cells can block blood flow causing pain which is referred as sickle cell crisis. This leads to a rigid, sickle-like shape to the cells under certain circumstances. The symptoms caused by the sickle cell disease include infections, pain and fatigue.

[0005] A typical measurement procedure for SCD detection involves invasive method where the extraction of fluids or cells are required from the human. The methods existed for the characterization of the hemoglobin disorders, for example the sickle cell disease include electrophoresis, high performance liquid chromatography (HPLC) and PCR based techniques. These techniques require well trained staff with well-maintained equipment with reasonable laboratory facilities. Currently the involved diagnostic methodologies are expensive, time-consuming and cannot be performed at the point-of-care.

[0006] Thus, there is a need for a non-invasive diagnostics for the sickle cell disease which can be performed at the point of care. A portable and battery operated device is required that does not require any blood samples for the diagnostics. A specially designed methodology is required for the SCD detection that avoids well trained staff with well maintained equipment. There is a requirement for a cost-effective and less time consuming SCD detection, through which the mass screening of even rural population can be accomplished without affecting their routine work. Therefore, an environmental friendly device is required which can be safe and easily operated by the normal staff.

Objectives of the invention:

[0007] The primary objective of the invention is to provide a non-invasive diagnostic device to identify sickle cell disease which can be performed at the point of care.

[0008] The other objective of the invention is to provide a portable and battery operated device for the diagnostics of the sickle cell disease.

[0009] The other objective of the invention is to detect the SCD using multi -wavelength radiating means through which light beam can be passed through the human finger tissue.

[0010] Another objective of the invention is to detect different wavelength absorbance responses from the human finger tissue at a varying magnetic field.

[0011] Another objective of the invention is to provide a special algorithm for accurate and rapid evaluation of the disease detection.

[0012] Another objective of the invention is to implement an algorithm by the controlling means of the device to process the absorbance responses from the human finger tissue and evaluate the parameters.

[0013] Another objective of the invention is to facilitate a cost-effective and less time consuming SCD detection through which mass screening of even rural population can be accomplished without affecting their routine work.

[0014] Another objective of the invention is to provide an accurate and amplified output signal using an amplifying and filtering means.

[0015] Further objective of the invention is to facilitate an environmental friendly device which can be easily operated by the normal staff without requiring any laboratory facility. Summary of the Invention:

[0016] The invention proposes a non invasive point of care diagnostics for sickle cell disease. The following presents a simplified summary in order to provide a basic understanding of some aspects of the claimed subject matter. This summary is not an extensive overview. It is not intended to identify key /critical elements or to delineate the scope of the claimed subject matter. Its sole purpose is to present some concepts in a simplified form as a prelude to the more detailed description that is presented later.

[0017] According to an exemplary aspect, the invention in general relates to a device and a method for identifying the sickle cell disease. The device utilizes a multi-wavelength radiating means and a magnetic means either separately or simultaneously for subsequent determination of the disease. More specifically, the invention relates to a non-invasive portable device for the direct measurement of the SCD through the absorbance levels of the light beam at different wavelengths. The absorbance levels of the light beam at different wavelengths are collected by applying varying magnetic field upon the tissue through the magnetic means. The varying magnetic field is accomplished in two conditions i.e., magnetic field ON condition and magnetic field OFF condition.

[0018] According to another exemplary aspect, the portable non-invasive device comprises, a multi-wavelength radiating means, a photo detecting means, a wavelength selector, a magnetic means such as an electromagnetic ring and an electromagnet excitation circuit, a pre-amplifier, a sampling and holding means, an amplifying and filtering means, a controlling means and a display. The multi-wavelength radiating means emanates light through the human finger tissue with at least one wavelength which is accomplished by the controlling means. At least one wavelength is selected through a wavelength selector.

[0019] The magnetic means is configured to apply a varying magnetic field on the human finger tissue i.e., the magnetic field is applied upon the tissue through the electromagnetic ring and the electromagnet excitation circuit. The absorbance response of light having said at least one wavelength is detected by the photo detecting means. The absorbance response of light at different wavelengths are collected during ON condition and OFF condition of the magnetic field. The detected absorbance response of light from the photo detecting means is pre-amplified by means of a pre-amplifier. The obtained output is separated into corresponding channel output through the sampling and holding means. Further, the channel output is processed by amplifying and filtering using amplifying and filtering means and is sent to the controlling means. The controlling means then manipulates the multi-wavelength radiating means and the magnetic means and then evaluates the disease parameters through an algorithm.

[0020] According to another aspect of the invention, the procedure of detecting sickle cell disease using non-invasive device comprises emanating light through the human finger tissue with at least one wavelength, applying a varying magnetic field on the human finger tissue, detecting absorbance response of light having said at least one wavelength, separating different absorbance response wavelengths into corresponding channels, processing channel output by amplifying and filtering, evaluating disease parameters through an algorithm and displaying evaluated diagnosis response.

[0021] According to another aspect of the invention, a specially designed algorithm for evaluating disease parameters comprises receiving light absorbance signals from a human finger tissue, computing ratios of different wavelength absorbance responses at varying magnetic field, considering the ratios of different wavelength absorbance responses as parametric responses of the human finger tissue, multiplying the parametric responses with scale factors and then adding, evaluating a critical number and finally comparing the critical number with a threshold value to confirm the disease.

[0022] The exemplary device is configured with the components as per the function described above, whereas the device can be further configured with other components or circuits or modules that aid either in the light transmission technique or absorption technique or evaluation technique of the disease. The algorithm which is implemented above by the controlling means for the evaluation of the parameters can be further simplified or modified or extended for the enhanced evaluation. The device apart from employing the disclosed components, can be equipped with other extended components that adds supplemental features to the device.

Description of Drawings:

[0023] The accompanying drawings, which are incorporated in and constitute a part of the specification, illustrate an embodiment of the invention, and, together with the description, serve to explain the principles of the invention.

[0024] Fig. 1 depicts a schematic form of a device 100 for non-invasive detection of the sickle cell disease according to an embodiment of the invention. [0025] Fig. 2 illustrates an exemplary procedure of sickle cell disease detection using noninvasive device.

[0026] Fig. 3 illustrates an exemplary designed algorithm for evaluating disease parameters according to an embodiment of the invention.

Detailed description of Drawings:

[0027] An exemplary embodiment of the present invention will be described in reference to the accompanying drawings. Wherever possible, same or similar reference numerals are used in the drawings and the description to refer to the same or like parts or steps.

[0028] According to an exemplary embodiment, Fig. 1 depicts a schematic form of a device 100 for non-invasive detection of the sickle cell disease. The device identifies the disease basing on different absorbance levels of the light beam at different wavelengths passing through the human finger tissue. The device 100 mainly consists of a multi-wavelength radiating means 101, a photo detecting means 102, a wavelength selector 103, a magnetic means such as an electromagnetic ring 104 and an electromagnet excitation circuit 105, a pre-amplifier 106, a sampling and holding means (S&H) 107, an amplifying and filtering means 108, a controlling means 109 and a display 110.

[0029] The multi-wavelength radiating means 101 may comprise a halogen bulb, LED or diode laser and thereof. As an example, the invention considers surface mount device (SMD) LEDs that are mounted in a specifically designed LED holder. This helps in emanating light as a narrow beam and which is then projected out. This projected light beam is passed over a human finger tissue as shown in fig. 1. The light beam reached out from the other side of the finger is detected by the photo detecting means 102. The photo detecting means 102 can be selected, based on the range of wavelengths that are chosen and also on the response time.

[0030] As an example during the process, each LED of the multi-wavelength radiating means 101 is glown for a short time interval with a selected wavelength using the wavelength selector 103. As the LED glows, the light beam passes through the finger and reaches the photo detecting means 102. The output from the photo detecting means 102 is amplified suitably, by means of a pre-amplifier 106. The output from the pre-amplifier 106 in turn is provided to the output channel which is selected and enabled by the corresponding activation of a particular wavelength LED. The separation of the different wavelength responses of the tissue to a corresponding channel can be achieved by placing an S&H circuit 107 at the input stage of each channel. The S&H circuit 107 of a corresponding channel is enabled, when the particular wavelength LED is glown. Therefore, the channel output is the absorbance response of the tissue for that particular wavelength. The output

from the S&H circuit 107 is further amplified and filtered using the amplifying and filtering means 108. This removes the switching noise and other noise signals.

[0031] In order to maintain time synchronism among the signals, all the channels are designed to have the similar time response characteristics. The channel outputs are provided to the controlling means 109 as analog signals. These analog signals are sampled by the controlling means 109 to perform the analysis.

[0032] The controlling means 109 controls the switching of different LEDs of the multi wavelength radiating means 101 and enables respective S&H circuits. The controlling means 109 is also responsible to control the electromagnetic ring 104 through electromagnet excitation circuit 105 to provide two different conditions i.e., ON and OFF. During the ON condition, the controlling means 109 applies magnetic field over the tissue and collects the tissue absorbance at different wavelengths in a time synchronized manner. The same process continues to collect the tissue absorbance during the OFF condition, where the magnetic field is not applied.

[0033] The controlling means 109 analyses the tissue absorbance signals by applying a specially designed algorithm and obtains certain parameters which are subsequently used to identify the sickle cell disease. The controlling means 109 is further provided with a closed feedback loop to obtain gain control. The evaluated diagnosis response is displayed on the display 110 which can be an LCD or visible diode display.

[0034] According to another exemplary embodiment of the invention, Fig. 2 represents a procedure of detecting sickle cell disease using non-invasive device 200. The procedure comprises emanating light through the human finger tissue with at least one wavelength at step 201. The light is emanated by means of the multi-wavelength radiating means. At step 202, a varying magnetic field is applied on the human finger tissue through an electromagnetic ring. At step 203, absorbance response of light from the tissue with at least one wavelength is detected. At step 204, different absorbance response wavelengths are separated into corresponding channels using a sampling and holding means. At step 205, the channel output is further processed by amplifying and filtering. At step 206, the disease parameters are evaluated using an algorithm and finally the evaluated diagnosis response is displayed on the display at step 207.

[0035] According to further exemplary embodiment of the invention, an algorithm for evaluating disease parameters is depicted in fig. 3. At step 301, the controlling means receives the channel outputs of the light absorbance signals from the human finger tissue. At step 302, the ratios of different wavelength absorbance responses are computed at varying magnetic field i.e., in two conditions of the magnetic field excitation given to the electromagnetic ring. For example, the wavelength absorbance responses are measured when the magnetic field is applied (ON condition) and also when the magnetic field is removed (OFF condition). At step 303, the ratios of different wavelength absorbance responses are considered as parametric responses of the human finger tissue. At step 304, the parameters are multiplied with scale factors and then the multiplied results are added. At step 305, a critical number is evaluated. At step 306, the critical number is compared with a threshold value. The threshold value can be obtained from the normal and the sickle cell readings. At step 307, the sickle cell disease is confirmed if the critical number is more than the threshold value. Otherwise the sickle cell disease is rejected and the person is considered normal.

[0036] The SCD disease can also be detected by considering other tissues such as a toe, an earlobe apart from the finger as mentioned in the complete description. The magnetic field applied by the electromagnetic ring can also be accomplished by the magnetic plates as well. Output from the controlling means can also be provided with an audio-visual alarm for real-time results. Further, a provision can be facilitated to store the information electronically.

[0037] Thus, the proposed device is a non-invasive diagnostics device to identify sickle cell disease which can be performed at the point of care. The device is a portable and battery operated through which the detection of the SCD can be accomplished using multi 10 wavelength radiating means. The output of different wavelength absorbance responses at a varying magnetic field is noted and computed with a special algorithm. The device facilitates a cost-effective and less time consuming SCD detection through which the mass screening of even rural population can be accomplished without affecting their routine work. Further, the invention facilitates an environmental friendly device which can be easily operated by the normal staff without requiring any laboratory facility. [0038] It will readily be apparent that numerous modifications and alterations can be made to the processes described in the foregoing examples without departing from the principles underlying the invention, and all such modifications and alterations are intended to be embraced by this application.

Claims

CLAIMS We Claim:

1. A device for non-invasive detection of sickle cell disease comprising: a multi-wavelength radiating means to emanate light through human finger tissue with at least one wavelength; a magnetic means to apply a varying magnetic field on said human finger tissue;

a photo detecting means to detect absorbance response of light having said at least one wavelength;

a sampling and holding means to separate different absorbance wavelengths from said photo detecting means into corresponding channels;

an amplifying and filtering means to process channel output from said sampling and holding means; and

a controlling means to manipulate said multi-wavelength radiating means, said magnetic means and to evaluate disease parameters through an algorithm.

2. The device for non-invasive detection of sickle cell disease as claimed in claim 1 , wherein said at least one wavelength is selected through a wavelength selector.

3. The device for non-invasive detection of sickle cell disease as claimed in claim 1, wherein said magnetic means may comprise an electromagnetic ring and an electromagnetic excitation circuit.

4. The device for non-invasive detection of sickle cell disease as claimed in claim 1 , wherein said varying magnetic field may be accomplished in two conditions i.e., ON and OFF.

5. The device for non-invasive detection of sickle cell disease as claimed in claim 1, wherein said absorbance response of light at different wavelengths are collected during magnetic field ON condition and OFF condition.

6. The device for non-invasive detection of sickle cell disease as claimed in claim 1 , wherein said detected absorbance response of light from said photo detecting means is preamplified by means of a pre-amplifier.

7. A procedure of detecting sickle cell disease using non-invasive device comprises:

emanating light through human finger tissue with at least one wavelength;

applying a varying magnetic field on said human finger tissue;

detecting absorbance response of light having said at least one wavelength;

separating different absorbance response wavelengths into corresponding channels;

processing channel output by amplifying and filtering;

evaluating disease parameters through an algorithm; and

displaying evaluated diagnosis response.

8. An algorithm for evaluating disease parameters comprises:

receiving light absorbance signals from a human finger tissue;

computing ratios of different wavelength absorbance responses at varying magnetic field; considering said ratios of different wavelength absorbance responses as parametric responses of said human finger tissue;

multiplying said parametric responses with scale factors and then adding;

evaluating a critical number; and

comparing said critical number with a threshold value to confirm disease.