WO2020053881A1

WO2020053881A1 - A device to detect stroke

Info

Publication number: WO2020053881A1
Application number: PCT/IN2019/050653
Authority: WO
Inventors: Rachit JHAVERI; Rupesh Ghyar; Sudheer AMBEKAR; Bhallamudi Ravi
Original assignee: Indian Institute Of Technology Bombay
Priority date: 2018-09-10
Filing date: 2019-09-10
Publication date: 2020-03-19

Abstract

A device to detect stroke, said device comprising: a sample well (101) to receive a blood sample; five biosensor strips, at a first level, each of said strip configured to receive a portion of a blood, said combination of test strips allowing reaction of biomarkers with said blood sample wherein reaction of said biomarkers with said blood sample displays whether a patient, whose blood sample is received on said sample well, has stroke or not and also displays type of stroke in case of detection of a stroke.

Description

A DEVICE TO DETECT STROKE

FIELD OF THE INVENTION:

This invention relates to the field of biomedical engineering.

Particularly, this invention relates to a device to detect stroke.

BACKGROUND OF THE INVENTION:

Stroke is one of the leading causes of death in the world and specifically in India. From the onset of stroke, a patient has a short window period (about 8-12 hours from onset of symptoms) during which interventions can be performed (surgically or using drugs) in order to minimize the damage caused by loss of blood supply to the brain because of a clot which causes the stroke. Beyond the window period, avoidance of future strokes and rehabilitation are the only options available and thus the damage caused by the first attack cannot be undone.

A patient who exhibits symptoms of stroke is clinically assessed and is sent for a CT scan. However, a CT scan may not show an infarct up to 6-8 hours of the onset of the stroke. MRI is a valuable imaging tool during a stroke; however, the numbers of nursing homes / diagnostic centres / hospitals providing an MRI scanner are few in metropolitan cities and this number steeply drops in rural areas. Another drawback of an MRI scan is the time it takes (approximately 45 minutes) for the procedure to be completed. If the CT scans do not definitely display an infarct, the patient is put on clot-busting drug (tPA), which, in itself, can cause hemorrhage in case of the absence of a stroke. It may also take a while for the patient to reach a multi- specialty hospital to get diagnosed with stroke due to a common trend of going to a general practitioner for initial assessment of any condition.

Majority of the patients who suffer a stroke visit a general physician and the symptoms being similar to conditions other than stroke, the patient is generally kept under observation. This may be catastrophic which is why faster diagnosis, in the event of a stroke, is required.

Faster diagnosis of stroke in the field would allow paramedics to alert hospitals sooner and have stroke specialists immediately available when the patient arrives. A similar approach has been used for years in cases of trauma, which allows specialized teams to be ready when a severely injured patient arrives.

Thus, a sensitive and specific device is required which can detect if the patient has stroke and the type of stroke. Also, an ambulance, hospital, and neurosurgeons need to be informed about the case so as to be instantly ready for further tests and treatment.

According to prior art, there are no devices that provide sensitive and specific stroke detection utilizing biomarkers. Some devices are in the prototype stage and involve wearable sensors which are less sensitive to stroke.

FIGURE 1 illustrates two types of strokes: 1) hemmorhagic; and 2) ischemic

FIGURE 2 illustrates treatment procedures in hospitals, following a stroke.

Following a stroke, the below-mentioned functional requirements are to be followed as protocol: Functional Requirement 1 : Confirmation of Stroke

Functional Requirement 2: Type of Stroke (Ischemic / Hemorrhagic / Both)

Functional Requirement 3: Outcome should be displayed in less than 15 minutes Functional Requirement 4: Notification system for ambulance, hospital, neurologist and neurosurgeon

OBJECTS OF THE INVENTION:

An object of the invention is to provide a device and methodology for early detection of stroke.

Another object of the invention is to provide a device and methodology to identify a plurality of biomarkers to ascertain a clinical condition or a medical condition of a person using the person’s blood sample.

Yet another object of the invention is to provide a device and methodology to identify a plurality of biomarkers to ascertain a whether a person has a stroke or not and to further identify the type of stroke using the person’s blood sample.

SUMMARY OF THE INVENTION:

According to this invention, there is provided a device to detect stroke, said device comprising:

a sample well configured to receive a blood sample;

five, horizontally spaced apart, biosensor strips, at a first level, each of said strip connected to said sample well and each of said strip being configured to receive a portion of a blood sample from said sample well, said combination of test strips allowing reaction of biomarkers with said blood sample using lateral flow immunoassay methodology wherein reaction of said biomarkers with said blood sample displays whether a patient, whose blood sample is received on said sample well, has stroke or not and also displays type of stroke in case of detection of a stroke;

a first biosensor strip, a second biosensor strip, a third biosensor strip, a fourth biosensor strip, and a fifth biosensor strip; each of said biosensors corresponding to a biomarker, thereby providing five biomarkers, characterised in that, said first biosensor strip being connected to said second biosensor strip at a second level beneath said first level through a separate first channel, said first biosensor strip being connected to said third biosensor strip at a second level beneath said first level through a separate second channel, said first biosensor strip being connected to said fourth biosensor strip at a second level beneath said first level through a separate third channel, said first biosensor strip being connected to said fifth biosensor strip at a second level beneath said first level through a separate fourth channel, and each of said first channel, said second channel, said third channel, and said fourth channel being connected to a detector; and

a detector employing a detector technique, comprising a selection of at least two of said biomarkers, through selection of a channel from said separate first channel, said separate second channel, said separate third channel, and said separate fourth channel, said detector being configured to detect whether said patient, whose blood sample has been collected, has suffered a stroke and further configured to detect a type of stroke with the help of said biomarkers, characterised in that,

o a first biosensor, configured to receive a portion of said blood sample, which indicates a first biomarker, said first biomarker being D-Dimer;

o a second biosensor, configured to receive a portion of said blood sample, which indicates a second biomarker said second biomarker being Matrix metallopeptidase 9 (MMP-9); o a third biosensor, configured to receive a portion of said blood sample, which indicates a third biomarker, said third biomarker being Highly sensitive C - reactive protein;

o a fourth biosensor, configured to receive a portion of said blood sample, which indicates a fourth biomarker, said fourth biomarker being SI 00 calcium- binding protein B (S100B);

o a fifth biosensor, configured to receive a portion of said blood sample, which indicates a fifth biomarker, said fifth biomarker being N-terminal pro brain natriuretic peptide (NT-proBNP).

Typically, said blood sample is made to react with at least a buffer solution that allow the flow of blood towards the reagent using lateral flow immunoassay technique, said buffer solutions facilitating anti-coagulation activity; thus, allowing blood to freely flow through the test strip.

Typically, said detector employs said detector technique, in that, if the level of said first biomarker and said second biomarker in the sampled blood is elevated, then, said detector detects confirmation of stroke for that blood sample.

Typically, said detector employs said detector technique, in that, if the level of said first biomarker and said third biomarker in the sampled blood are highly elevated, then, said detector detects confirmation of Ischemic stroke for that blood sample.

Typically, said detector employs said detector technique, in that, if the level of said fifth biomarker in the sampled blood is high, then, said detector detects confirmation of stroke, of cardio embolic origin, for that blood sample. Typically, said detector employs said detector technique, in that, if the level of said first biomarker and said fourth biomarker in the sampled blood are elevated, then, said detector detects confirmation of hemorrhagic stroke for that blood sample.

Typically, said device comprises a display to provide an output if the patient, whose blood sample has been drawn, has suffered a stroke or not and the type of stroke.

Typically, said device comprises a display to provide an output if the patient, whose blood sample has been drawn, has suffered a stroke or not and the type of stroke, characterised in that, said display comprising a test region band and control region band.

Typically, said device comprises a display to provide an output if the patient, whose blood sample has been drawn, has suffered a stroke or not and the type of stroke, characterised in that, said display comprising a test region band and control region band and for positive test results, one band appears in said control region and another band appears in said test region.

Typically, said device comprises a display to provide an output if the patient, whose blood sample has been drawn, has suffered a stroke or not and the type of stroke, characterised in that, said display comprising a test region band and control region band and for negative test results, one coloured band appears in said control region and no band appears in said test region.

Typically, said device comprises a display to provide an output if the patient, whose blood sample has been drawn, has suffered a stroke or not and the type of stroke, characterised in that, said display comprising a test region band and control region band and for invalid test results, no band appears in said control region and no band appears in said test region.

BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWINGS:

FIGURE 1 illustrates two types of strokes: 1) hemmorhagic; and 2) ischemic; and FIGURE 2 illustrates treatment procedures in hospitals, following a stroke.

The invention will now be described in relation to the accompanying drawings, in which:

FIGURE 3 shows a methodology for differentiating a stroke from stroke mimics and also determination of stroke subtype;

FIGURE 4 illustrates a schematic side view of the device for the methodology of Figure 1 ;

FIGURE 5 illustrates a schematic top view of the device for the methodology of Figure 1 ;

FIGURE 6 illustrates a tabulated list of biomarkers to detect stroke; and FIGURE 7 illustrates an overall system architecture using the device of Figure 1.

DETAILED DESCRIPTION OF THE ACCOMPANYING DRAWINGS:

According to this invention, there is provided a device to detect stroke.

FIGURE 3 shows a methodology for differentiating a stroke from stroke mimics and also determination of stroke subtype.

In at least an embodiment blood sample from a person / patient is collected by finger pricking and is administered in a sample well (101).

In at least an embodiment, a combination of test strips is provided which receive portions of the collected blood sample. This combination of test strips allows reaction of biomarkers with the blood sample using lateral flow immunoassay methodology. The blood sample may or may not be made to react with buffer solutions that allow the flow of blood towards the reagent using lateral flow immunoassay technique. These buffer solutions facilitate anti-coagulation activity; thus, allowing the blood to freely flow through the test strip. Reaction of biomarkers with the blood sample displays whether the patient has stroke or not and the type of stroke. Each test strip has a calibrated control line and a calibrated test line.

In at least an embodiment, five biomarkers are identified and used with the device of this invention. This is done by the means of five biosensors; each biosensor corresponding to a biomarker.

Typically, a portion of blood sample is fed to a first biosensor (102) which indicates a first biomarker namely D-Dimer. D-dimer (or D dimer) is a fibrin degradation product (or FDP), a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis. Ordinarily, D-dimer concentration may be determined by a blood test to help diagnose thrombosis. Since its introduction in the 1990s, it has become an important test performed in patients with suspected thrombotic disorders. Although, D-Dimer has been known, ordinarily, for detection of thrombosis, but by virtue of the design of the device of this invention - which, essentially, is a multi-channel device providing combinations of markers in a previously unknown manner to achieve a calibrated, rapid, detection of, not only a stroke but also, the type of stroke - at point of care; which provided technical advantage and benefits to the medical fraternity within the golden hour so as to provide fast diagnosis and dispense accurate treatment based on the diagnosis.

Typically, a portion of blood sample is fed to a second biosensor (103) which indicates a second biomarker namely Matrix metallopeptidase 9 (MMP-9). Matrix metallopeptidase 9 (MMP-9), also known as 92 kDa type IV collagenase, 92 kDa gelatinase or gelatinase B (GELB), is a matrixin, a class of enzymes that belong to the zinc-metalloproteinases family involved in the degradation of the extracellular matrix. MMP9 has been found to be associated with numerous pathological processes, including cancer, placental malaria, immunologic and cardiovascular diseases. Although, MMP9 has been, ordinarily, known for detection of numerous pathological processes, but by virtue of the design of the device of this invention - which, essentially, is a multi-channel device providing combinations of markers in a previously unknown manner to achieve a calibrated, rapid, detection of, not only a stroke but also, the type of stroke - at point of care; which provided technical advantage and benefits to the medical fraternity within the golden hour so as to provide fast diagnosis and dispense accurate treatment based on the diagnosis.

Typically, a portion of blood sample is fed to a third biosensor (104) which indicates a third biomarker namely Highly sensitive C - reactive protein. A high- sensitivity C-reactive protein (hs-CRP) test, which is more sensitive than a standard test, also can be used to evaluate your risk of developing coronary artery disease, a condition in which the arteries of your heart are narrowed. Coronary artery disease can lead to a heart attack. High- sensitivity C-reactive protein is produced by the body when blood-vessel walls are inflamed. The higher your levels of hs-CRP, the higher your levels of inflammation tend to be. Although, Highly sensitive C - reactive protein has been, ordinarily, known for detection of inflammations using blood, but by virtue of the design of the device of this invention - which, essentially, is a multi-channel device providing combinations of markers in a previously unknown manner to achieve a calibrated, rapid, detection of, not only a stroke but also, the type of stroke - at point of care; which provided technical advantage and benefits to the medical fraternity within the golden hour so as to provide fast diagnosis and dispense accurate treatment based on the diagnosis.

Typically, a portion of blood sample is fed to a fourth biosensor (105) which indicates a fourth biomarker namely S100 calcium-binding protein B (S100B). SI 00 calcium-binding protein B (S100B) is a protein of the S-100 protein family. SI 00 proteins are localized in the cytoplasm and nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100B is secreted by astrocytes or can spill from injured cells and enter the extracellular space or bloodstream. Serum levels of S100B increase in patients during the acute phase of brain damage. Over the last decade, S100B has emerged as a candidate peripheral biomarker of blood-brain barrier (BBB) permeability and CNS injury. Elevated S100B levels accurately reflect the presence of neuropathological conditions including traumatic head injury or neurodegenerative diseases. Although, S100B has been, ordinarily, known for detection of numerous neuropathological conditions, but by virtue of the design of the device of this invention - which, essentially, is a multi-channel device providing combinations of markers in a previously unknown manner to achieve a calibrated, rapid, detection of, not only a stroke but also, the type of stroke - at point of care; which provided technical advantage and benefits to the medical fraternity within the golden hour so as to provide fast diagnosis and dispense accurate treatment based on the diagnosis.

Typically, a portion of blood sample is fed to a fifth biosensor (106) which indicates a fifth biomarker namely N-terminal pro brain natriuretic peptide (NT- proBNP). The N-terminal prohormone of brain natriuretic peptide (NT-proBNP or BNPT) is a prohormone with a 76 amino acid N-terminal inactive protein that is cleaved from the molecule to release brain natriuretic peptide.

Both BNP and NT-proBNP levels in the blood are used for screening, diagnosis of acute congestive heart failure (CHF) and may be useful to establish prognosis in heart failure, as both markers are typically higher in patients with worse outcome. N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing is useful for diagnosing acute decompensated heart failure. Although, NT-proBNP has been, ordinarily, known for establish prognosis in heart failure, but by virtue of the design of the device of this invention - which, essentially, is a multi-channel device providing combinations of markers in a previously unknown manner to achieve a calibrated, rapid, detection of, not only a stroke but also, the type of stroke - at point of care; which provided technical advantage and benefits to the medical fraternity within the golden hour so as to provide fast diagnosis and dispense accurate treatment based on the diagnosis.

In at least an embodiment, a detector is configured to detect whether the patient, whose blood sample has been collected, has suffered a stroke and also detects the type of stroke with the help of these biomarkers. Typically, the detector implements a technique to capture the levels of biomarkers in the blood sample that was appropriated to each corresponding biosensor.

In at least an embodiment of the detector technique, if the level of D-Dimer and MMP-9 in the sampled blood is elevated, the patient (whose blood sample was collected) can be confirmed to have stroke.

In at least an embodiment of the detector technique, if the levels of D-Dimer and Highly sensitive C-Reactive Protein are highly elevated, the patient (whose blood sample was collected) can be confirmed to have Ischemic stroke.

In at least an embodiment of the detector technique, if the levels of N-terminal pro brain natriuretic peptide are high, the patient (whose blood sample was collected) can be confirmed to have stroke which is of cardio embolic origin.

In at least an embodiment of the detector technique, if the levels of levels of D- Dimer and S100B are elevated, the patient (whose blood sample was collected) can be confirmed to have hemorrhagic stroke.

In at least an embodiment, a display section provides an output if the subject has suffered a stroke or not and the type of stroke. For positive test results, one band appears in a control region and another band appears in a test region. For negative test results, only one coloured band appears in the control region and no apparent coloured band appears in the test region. For invalid test results, the control band fails to appear or none of the bands appear.

FIGURE 3 depicts a complete block diagram of the point of care device for stroke detection along with stroke-type detection. The whole blood (101) is fed to the sample well. The biosensors (102, 103, 104, 105, 106) for each of the five biomarkers display the level of biomarker in the blood..

FIGURE 4 illustrates a schematic side view of the device for the methodology of Figure 1.

In at least an embodiment, strips (102, 103, 104, 105, 106) with biomarkers are laid on a bottom surface)e / housing (307. A camera (300) is positioned an an operative top surface / housing (305) such that its field of view captures all the strips in a unified view. A microcontroller (201) to detect stroke and type of stroke as well as a display (203) are provided in the housing

FIGURE 5 illustrates a schematic top view of the device for the methodology of Figure 1.

FIGURE 6 illustrates a tabulated list of biomarkers to detect stroke.

FIGURE 7 illustrates an overall system architecture using the device of Figure 1.

In at least an embodiment, the system is configured with a communication module to communicate its findings to a communicably coupled remote node such as an ambulance and / or a doctor and / or a hospital and / or a laboratory and / or a test centre.

Reference numeral 201 refers to a microcontroller module.

Reference numeral 202 refers to a GPS module.

Reference numeral 203 refers to a display module.

Reference numeral 204 refers to an ambulance notification module. Reference numeral 205 refers to a hospital notification module.

Reference numeral 206 refers to a neurologist / neurosurgeon notification module.

The TECHNICAL ADVANCEMENT of this invention lies in providing a device which validates if a person has a stroke and also accurately identifies the type of stroke for a person; using the person’s blood sample. This is critical rather, in the interest of time, since it validates the type of stroke apart from simply concluding that a patient has suffered a stroke. This parameter is important since the type of stroke is critically important for the line of treatment. Ischemic and hemorrhagic strokes have significantly different line of treatments thus aiding the hospital in prescribing further tests (CT or MRI or other gold standards)

While this detailed description has disclosed certain specific embodiments for illustrative purposes, various modifications will be apparent to those skilled in the art which do not constitute departures from the spirit and scope of the invention as defined in the following claims, and it is to be distinctly understood that the foregoing descriptive matter is to be interpreted merely as illustrative of the invention and not as a limitation.

Claims

CLAIMS,

1. A device to detect stroke, said device comprising:

- a sample well (101) configured to receive a blood sample;

- five, horizontally spaced apart, biosensor strips, at a first level, each of said strip connected to said sample well and each of said strip being configured to receive a portion of a blood sample from said sample well, said combination of test strips allowing reaction of biomarkers with said blood sample using lateral flow immunoassay methodology wherein reaction of said biomarkers with said blood sample displays whether a patient, whose blood sample is received on said sample well, has stroke or not and also displays type of stroke in case of detection of a stroke;

- a first biosensor strip, a second biosensor strip, a third biosensor strip, a fourth biosensor strip, and a fifth biosensor strip; each of said biosensors corresponding to a biomarker, thereby providing five biomarkers, characterised in that, said first biosensor strip being connected to said second biosensor strip at a second level beneath said first level through a separate first channel, said first biosensor strip being connected to said third biosensor strip at a second level beneath said first level through a separate second channel, said first biosensor strip being connected to said fourth biosensor strip at a second level beneath said first level through a separate third channel, said first biosensor strip being connected to said fifth biosensor strip at a second level beneath said first level through a separate fourth channel, and each of said first channel, said second channel, said third channel, and said fourth channel being connected to a detector; and

- a detector employing a detector technique, comprising a selection of at least two of said biomarkers, through selection of a channel from said separate

1 first channel, said separate second channel, said separate third channel, and said separate fourth channel, said detector being configured to detect whether said patient, whose blood sample has been collected, has suffered a stroke and further configured to detect a type of stroke with the help of said biomarkers, characterised in that,

o a first biosensor (102), configured to receive a portion of said blood sample, which indicates a first biomarker, said first biomarker being D-Dimer;

o a second biosensor (103), configured to receive a portion of said blood sample, which indicates a second biomarker said second biomarker being Matrix metallopeptidase 9 (MMP-9); o a third biosensor (104), configured to receive a portion of said blood sample, which indicates a third biomarker, said third biomarker being Highly sensitive C - reactive protein;

o a fourth biosensor (105), configured to receive a portion of said blood sample, which indicates a fourth biomarker, said fourth biomarker being S100 calcium-binding protein B (S100B);

o a fifth biosensor (106), configured to receive a portion of said blood sample, which indicates a fifth biomarker, said fifth biomarker being N-terminal pro brain natriuretic peptide (NT-proBNP).

2. The device as claimed in claim 1 wherein, said blood sample being made to react with at least a buffer solution that allow the flow of blood towards the reagent using lateral flow immunoassay technique, said buffer solutions facilitating anti-coagulation activity; thus, allowing blood to freely flow through the test strip.

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3. The device as claimed in claim 1 wherein, said detector employing said detector technique, in that, if the level of said first biomarker and said second biomarker in the sampled blood is elevated, then, said detector detects confirmation of stroke for that blood sample.

4. The device as claimed in claim 1 wherein, said detector employing said detector technique, in that, if the level of said first biomarker and said third biomarker in the sampled blood are highly elevated, then, said detector detects confirmation of Ischemic stroke for that blood sample.

5. The device as claimed in claim 1 wherein, said detector employing said detector technique, in that, if the level of said fifth biomarker in the sampled blood is high, then, said detector detects confirmation of stroke, of cardio embolic origin, for that blood sample.

6. The device as claimed in claim 1 wherein, said detector employing said detector technique, in that, if the level of said first biomarker and said fourth biomarker in the sampled blood are elevated, then, said detector detects confirmation of hemorrhagic stroke for that blood sample.

7. The device as claimed in claim 1 wherein, said device comprising a display to provide an output if the patient, whose blood sample has been drawn, has suffered a stroke or not and the type of stroke.

8. The device as claimed in claim 1 wherein, said device comprising a display to provide an output if the patient, whose blood sample has been drawn, has suffered a stroke or not and the type of stroke, characterised in that, said display comprising a test region band and control region band.

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9. The device as claimed in claim 1 wherein, said device comprising a display to provide an output if the patient, whose blood sample has been drawn, has suffered a stroke or not and the type of stroke, characterised in that, said display comprising a test region band and control region band and for positive test results, one band appears in said control region and another band appears in said test region.

10. The device as claimed in claim 1 wherein, said device comprising a display to provide an output if the patient, whose blood sample has been drawn, has suffered a stroke or not and the type of stroke, characterised in that, said display comprising a test region band and control region band and for negative test results, one coloured band appears in said control region and no band appears in said test region.

11. The device as claimed in claim 1 wherein, said device comprising a display to provide an output if the patient, whose blood sample has been drawn, has suffered a stroke or not and the type of stroke, characterised in that, said display comprising a test region band and control region band and for invalid test results, no band appears in said control region and no band appears in said test region.

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