Method and system for measuring biomarkers by using smart contact lens

Abstract

A system and a method for measuring biomarkers by using a smart contact lens, according to one embodiment of the present invention, comprise: a smart contact lens worn on the eye of a subject so as to measure biomarkers in tears; and a terminal equipped with an application for collecting data of the biomarkers in tears from the smart contact lens, wherein the terminal includes a control unit for controlling that biomarkers in tears are measured after a stabilization time has elapsed from when the smart contact lens is worn on the eye of the subject.

Description

Biomarker measurement method and system using smart contact lenses

[0001] The present invention relates to a method and system for measuring biomarkers using smart contact lenses.

[0002] There have been numerous attempts to measure various biosignals present in the eye using smart contact lenses. These biosignals can be measured directly or via a wireless communication reader. For example, smart contact lenses exist that measure chemical factors such as sugar, cholesterol, cortisol, MMP-9, and uric acid, as well as physical factors such as intraocular pressure, electroretinogram (ERG), and temperature.

[0003] However, existing measurement methods do not account for the instability of smart contact lenses when measuring biosignals, resulting in inaccurate results. Specifically, immediately after wearing the lenses, the eyes are irritated, causing reflex tears. However, reflex tears contain chemical elements with different concentrations than basal tears, so if measurements are made without considering this, reflex tears can lead to significant errors in concentration measurements.

[0004] Meanwhile, since chemical elements present in tears diffuse into the bloodstream, there is a delay before these elements enter the tears. Therefore, when simultaneously measuring chemical elements in tears and blood, the trend in the tear chemical element concentration graph will be delayed by the blood concentration.

[0005] However, previous studies did not take this delay into account, and it was difficult to accurately match the concentration measurements of chemical elements in tears with the predictions of chemical elements in blood.

[0006] (Patent Document 1) Registered Patent Publication No. 10-2483190

[0007] The present invention provides an accurate biomarker measurement method and measurement system that introduces a time for stabilization of a tear layer when measuring biomarkers using a smart contact lens as a method for solving the problems of the above-described prior art.

[0008] The technical problems to be solved by the present invention are not limited to the technical problems mentioned above, and other technical problems not mentioned can be clearly understood by a person having ordinary skill in the technical field to which the present invention belongs from the description below.

[0009] In order to achieve the above technical task, one embodiment of the present invention provides a biomarker measurement system using a smart contact lens.

[0010] A biomarker measurement system using a smart contact lens according to one embodiment of the present invention includes: a smart contact lens that is worn on the eye of a subject to measure a biomarker in tears; and a terminal equipped with an application that collects data on the biomarker in tears from the smart contact lens; wherein the terminal includes a control unit that controls the smart contact lens to measure the biomarker in tears after a stabilization time has elapsed since the smart contact lens is worn on the eye of the subject to measure.

[0011] In an embodiment of the present invention, the stabilization time may be a biomarker measurement system using a smart contact lens, characterized in that it is a predetermined time for the first tear layer present at the time of wearing the smart contact lens to return to a state suitable for measuring the biomarker in the tear, and is 1 minute or more.

[0012] In an embodiment of the present invention, the biomarker in the tear may be a biomarker measurement system using a smart contact lens, characterized in that at least one biomarker in the tear is selected from the group consisting of Glucose, MMP-9, Lactoferrin, Cortisol, α-defensins, Cholesterol, and uric acid.

[0013] In an embodiment of the present invention, the terminal may be a biomarker measurement system using a smart contact lens, characterized in that it further includes a notification unit that provides a notification when the stabilization time is required.

[0014] In an embodiment of the present invention, the terminal may be a biomarker measurement system using a smart contact lens, characterized in that it further includes an analysis unit that analyzes and processes the collected data of biomarkers in tears to generate and provide body condition information.

[0015] In an embodiment of the present invention, the terminal may further include a delay time input unit capable of inputting a delay time between the biomarker in the tear and the body condition information, and the analysis unit may be a biomarker measurement system using a smart contact lens, characterized in that it generates the body condition information based on the delay time input to the delay time input unit.

[0016] In an embodiment of the present invention, the terminal may further include a conversion formula input unit capable of inputting a conversion formula, and the analysis unit may be a biomarker measurement system using a smart contact lens, characterized in that it generates the body condition information based on the delay time input into the delay time input unit and the conversion formula input into the conversion formula input unit.

[0017] Another embodiment of the present invention for achieving the above technical task provides a method for measuring a biomarker using a smart contact lens.

[0018] A method for measuring a biomarker using a smart contact lens according to one embodiment of the present invention is characterized by including a step of controlling a stabilization time when the smart contact lens is worn on the eye of a subject; and a step of measuring a biomarker in tears using the smart contact lens.

[0019] According to an embodiment of the present invention, in a method for measuring a biomarker in tears using a smart contact lens, there is an effect of introducing a stabilization time to eliminate errors caused by reflected tears and accurately measure chemical elements in tears.

[0020] In particular, since it is possible to measure the concentration of chemical elements only in basic tears that are highly correlated with blood, the measurement accuracy is significantly increased.

[0021] In addition, in a system for measuring biomarkers in tears using smart contact lenses, the concept of delay time can be introduced to compensate for the delay in biomarker data in tears compared to actual blood body condition data.

[0022] The effects of the present invention are not limited to the effects described above, and should be understood to include all effects that can be inferred from the detailed description of the present invention or the composition of the invention described in the claims.

[0023] FIG. 1 is a conceptual diagram illustrating a biomarker measurement system using a smart contact lens according to one embodiment of the present invention.

[0024] Figure 2 is a diagram showing the results of observing changes in tear volume and tear sugar after wearing smart contact lenses in rabbits.

[0025] FIG. 3 is a drawing showing a biomarker measurement method using a smart contact lens according to one embodiment of the present invention.

[0026] FIG. 4 is a diagram illustrating a biomarker measurement system using a smart contact lens according to one embodiment of the present invention.

[0027] FIG. 5 is a diagram illustrating a biomarker measurement system according to one embodiment of the present invention including a notification function.

[0028] Figure 6 is a graph comparing the results of measuring tear glucose using a biomarker measurement system according to one embodiment of the present invention with the results of measuring blood glucose.

[0029] Figure 7 is a graph showing the delay time results on days 1, 3, and 5 in 10 normal people and 10 diabetic patients.

[0030] Figure 8 shows the results of correlation analysis with blood sugar and matching error grid analysis after applying the delay time value to the measured tear data.

[0031] FIG. 9 is a diagram illustrating an application of a biomarker measurement system using a smart contact lens according to one embodiment of the present invention.

[0032] Hereinafter, the present invention will be described with reference to the attached drawings. However, the present invention can be implemented in various different forms and is therefore not limited to the embodiments described herein. In the drawings, irrelevant parts have been omitted for clarity of description, and similar parts have been designated with similar reference numerals throughout the specification.

[0033] Throughout the specification, when a part is said to be "connected (connected, contacted, or coupled)" to another part, this includes not only cases where it is "directly connected," but also cases where it is "indirectly connected" with another part in between. Furthermore, when a part is said to "include" a component, this does not exclude other components, but rather implies that it may include other components, unless otherwise specifically stated.

[0034] The terminology used herein is merely used to describe specific embodiments and is not intended to limit the present invention. The singular expression includes the plural expression unless the context clearly indicates otherwise. In this specification, it should be understood that the terms "comprises" or "has" indicate the presence of a feature, number, step, operation, component, part, or combination thereof described in the specification, but do not exclude in advance the possibility of the presence or addition of one or more other features, numbers, steps, operations, components, parts, or combinations thereof.

[0035] Hereinafter, embodiments of the present invention will be described in detail with reference to the attached drawings.

[0036]

[0037] A method and system for measuring a biomarker using a smart contact lens according to one embodiment of the present invention are described.

[0038] Biomarkers are biological indicators that can measure the body's condition, including blood pressure, body temperature, and heart rate. In addition to the physical factors mentioned above, substances found within the body, namely chemical elements, are also used as important biomarkers. However, biomarkers found in blood require invasive measurement, which can be painful during repeated measurements. Therefore, healthcare devices that utilize chemical elements found in bodily fluids such as tears and saliva, rather than blood, as biomarkers for non-invasive measurement have become a necessity.

[0039] Accordingly, a smart contact lens, which is a healthcare device capable of measuring chemical elements in tears, was designed. In the present invention, the 'smart contact lens' refers to a device that is mounted on the eye and can measure chemical elements (biomarkers) in tears.

[0040] FIG. 1 is a conceptual diagram illustrating a biomarker measurement system using a smart contact lens according to one embodiment of the present invention.

[0041] As described above, smart contact lenses are worn on the human eye to measure biomarkers, which are chemical elements in tears. A smart device or a wireless communication reader, as shown in FIG. 1, may be suggested as a means for collecting measured biomarker data. Furthermore, although not illustrated in FIG. 1, the smart contact lens itself may include a communication device, etc., so that the measured data can be collected by a terminal. Furthermore, the present invention also encompasses a smart contact lens in which the lens itself is composed of a material whose optical properties change in response to biomarkers in tears, and which can be observed from the outside. In other words, the technical idea of ​​the present invention is that the smart contact lens is sufficient as a device that can be worn on the eye to measure biomarkers in tears, and is not limited to the method of data collection.

[0042] Meanwhile, existing measurement methods measured biosignals without considering the unstable state after wearing smart contact lenses, resulting in inaccurate results.

[0043] Accordingly, the main purpose of the present invention is to provide a method for measuring biomarkers accurately by introducing a stabilization time in a method for measuring biomarkers using a smart contact lens.

[0044] In the present invention, the stabilization time refers to the time from the time of wearing the smart contact lens until the first tear layer present in the eye becomes suitable for measuring a biomarker.

[0045] There are three types of tears: basal tears, reflex tears, and emotional tears. Basal and reflex tears differ in their composition. Furthermore, the initial corneal irritation experienced when wearing smart contact lenses triggers reflex tears, which in turn alter tear volume and the concentration of chemical components within the tear. These concentration changes can lead to errors in the measurement of tear biomarkers.

[0046] Additionally, contact lens materials have a high moisture content for comfortable wearing, and since the lenses must be stored together with lens solution, there is a problem that the tear components are diluted by the lens solution when the smart contact lenses are first worn.

[0047] Accordingly, there is a need to solve the above-described problems in biomarker measurement methods using smart contact lenses.

[0048]

[0049] The inventors of the present invention have noted that the tear film within the eye remains stable even when chemical element concentrations change due to the tear circulation process of tear secretion and tear drainage. Accordingly, the present invention addresses this issue by introducing a step that allows for the stabilization of the tear film to occur over time.

[0050] Figure 2 is a diagram showing the results of observing changes in tear volume and tear sugar after wearing smart contact lenses in rabbits.

[0051] We observed changes in tear volume and tear glucose levels in four normal rabbits after wearing smart contact lenses. Figure 2 illustrates the experimental results. Immediately after wearing the smart contact lenses, tear volume and tear glucose levels experienced a rapid and unstable state, with the levels stabilizing after a certain recovery period. Therefore, it is important to allow at least one minute of stabilization time after wearing the smart contact lenses.

[0052] FIG. 3 is a drawing showing a biomarker measurement method using a smart contact lens according to one embodiment of the present invention.

[0053] Accordingly, one embodiment of the present invention proposes a biomarker measurement method using a smart contact lens, as shown in FIG. 3, including a step (S100) of controlling a stabilization time when the smart contact lens is worn on the eye of a subject; and a step (S200) of measuring a biomarker in tears using the smart contact lens.

[0054] The above smart contact lens, as described above, includes all types of smart contact lenses that can be worn on the eye of a subject to measure biomarkers in tears. For example, these may be smart contact lenses with built-in sensors that transmit data to an external terminal via wireless communication, or they may be contact lenses in which the lens itself is composed of a material that changes its optical properties in response to biomarkers in tears, enabling the measurement of bodily conditions by observing optical changes in the lens from the outside. In other words, any smart contact lens that can be worn on the eye to measure biomarkers in tears is sufficient, and there are no technical limitations on the measurement method.

[0055] For example, the stabilization time may be one minute or longer. Because it is difficult for the concentration of chemical elements within the tear film to stabilize in times shorter than one minute, the stabilization time should be set to one minute or longer. Furthermore, while the time it takes for the tear film to stabilize may vary from person to person, the difference is not significant, so a constant stabilization time value can be used.

[0056] For example, chemical elements that can be biomarkers measured by the smart contact lens may include, for example, Glucose, MMP-9, Lactoferrin, Cortisol, α-defensins, Cholesterol, or uric acid. However, this is not limited to these, and any type of biomarker substance that exists in tears and can be an indicator of bodily condition information may be included.

[0057] Meanwhile, as a means of implementing a biomarker measurement method using a smart contact lens that introduces a stabilization time as described above, a measurement system that controls the smart contact lens using an application such as a user terminal to ensure a stabilization time may be proposed. However, the technical concept of the present invention is not limited to such means, and any type of means capable of controlling the stabilization time may be included.

[0058] FIG. 4 is a diagram illustrating a biomarker measurement system using a smart contact lens according to one embodiment of the present invention.

[0059] A biomarker measurement system using a smart contact lens according to an embodiment of the present invention includes a smart contact lens (10) that can measure a biomarker in tears by being worn on the eye of a subject as shown in FIG. 4; and a terminal (30) equipped with an application (20) that collects the biomarker in tears of the subject from the smart contact lens (10); and the terminal (30) is characterized in that it includes a control unit (31) that controls the measurement of the biomarker in tears after a stabilization time has passed since the smart contact lens was worn on the eye of the subject.

[0060] For example, the stabilization time may likewise be 1 minute or longer. Accordingly, when the stabilization time is required, the control unit (31) initiates measurement. As a specific example, the control unit (31) may automatically initiate measurement of biomarkers in tears when the stabilization time is required, or may display a measurement initiation button on the terminal screen display when the stabilization time is required, and the terminal user may initiate measurement when the button is pressed.

[0061] FIG. 5 is a diagram illustrating a biomarker measurement system according to one embodiment of the present invention including a notification function.

[0062] According to one example, the terminal (30) of the biomarker measurement system may further include a notification unit (32) that provides a notification when a stabilization time is required. For example, as shown in FIG. 5, if a stabilization time (e.g., 1 minute) is required after the subject wears the smart contact lens, a function may be added to cause the notification unit (32) of the terminal to vibrate or make a sound, so that when the stabilization time is required, the user may be guided to immediately control the measurement of the biomarker in the tear through a button, or the user may be notified that the measurement has automatically started.

[0063] In addition, in a biomarker measurement system using a smart contact lens according to an embodiment of the present invention, the terminal (30) may further include an analysis unit (33) that analyzes and processes the collected data of biomarkers in tears to generate and provide body condition information.

[0064] According to one example, the analysis unit (33) may analyze the collected biomarker data, generate real-time body condition information therefrom, and provide it in the form of a graph on the display screen of the terminal.

[0065] As a specific example, it can be assumed that the smart contact lens (10) corresponds to a smart contact lens that measures the concentration of glucose, which is a biomarker in tears. At this time, the concentration data of glucose measured by the smart contact lens (10) is collected on the application (20) installed on the terminal (30). The analysis unit (33) can analyze and process this into a graph of the subject's real-time blood glucose level, which is physical condition information, and provide it on the display screen. That is, the system further includes the analysis unit (33) to generate and provide physical condition information based on the measured biomarker in tears.

[0066] Meanwhile, in the process of generating body condition information through biomarker data in tears through the above analysis unit (33), it became necessary to introduce the concept of lag time as in the following experimental example. Lag time refers to the time difference between the measured value of the biomarker in the blood and the actual body condition information in the blood, which is caused by the time it takes for the components in the blood to diffuse into the tear layer. This is due to the plasma leakage phenomenon. In the experimental example of the present invention, it was found that the time lag phenomenon commonly occurred in rabbits, beagles, humans, etc., and in order for the analysis unit (33), which is a component of the present invention, to generate and provide body condition information based on biomarkers in tears, this lag time must be reflected.

[0067] Figure 6 is a graph comparing the results of measuring tear glucose using a biomarker measurement system according to one embodiment of the present invention with the results of measuring blood glucose.

[0068] A healthy individual consumed a carbonated beverage, and their tear glucose levels were measured using a smart contact lens for 120 minutes, while their blood glucose levels were simultaneously measured using a glucometer. The measured tear glucose levels were displayed at one-minute intervals, and their blood glucose levels at five-minute intervals. As shown in Figure 6, the tear glucose and blood glucose levels exhibited a lag time.

[0069] Figure 7 is a graph showing the delay time results on days 1, 3, and 5 in 10 normal people and 10 diabetic patients.

[0070] As shown in the above figure 7, when the delay time values ​​were measured for 10 normal people and 10 diabetic patients, it can be seen that there is a large difference in the delay time values ​​between each individual, but it can be seen that the delay time values ​​on the 1st, 3rd, and 5th days of an individual do not change significantly, and therefore it is estimated that the delay time values ​​do not change significantly in the short term.

[0071] Figure 8 shows the results of correlation analysis with blood sugar and matching error grid analysis after applying the delay time value to the measured tear data.

[0072] Looking at the Pearson correlation analysis graph of Figure 8 above, it can be seen that the Pearson correlation coefficient r is 0.9 or higher for both normal people and diabetic patients, indicating a very high correlation.

[0073] Additionally, we performed a concordance error grid analysis between the blood glucose values ​​converted through tear glucose and the actual measured blood glucose values ​​by applying the delay time value. The concordance error grid is an analysis method used to evaluate the clinical validity of actual commercial blood glucose meters, and clinical validity is indicated when all data points are located in zones A and B. As shown in Fig. 8, it can be observed that all data points of the blood glucose values ​​with the delay time applied are located in zones A and B, as shown in Fig. 8.

[0074] In the end, as in the experimental example of Fig. 6 described above, it can be seen that the 'actual blood biomarker' of the subject has a time difference equal to the delay time from the biomarker in tears.

[0075] In addition, in the experimental examples of FIGS. 7 and 8 described above, when delay time correction processing is performed, the actual blood sugar value and the converted blood sugar value have a very high correlation, and it can be seen that the results of the matching error grid analysis are also clinically valid.

[0076] Therefore, in the measurement system according to one embodiment of the present invention, an accurate biomarker measurement system can be provided in which an additional delay time is introduced in the process of the analysis unit (33) generating body condition information based on the biomarker in tears.

[0077] Accordingly, in the biomarker measurement system of the present invention, the physical condition information provided by the analysis unit (33) may be generated based on the delay time from the data of the biomarker in the collected tears.

[0078] For example, if the delay time value of the subject is 15 minutes, the physical condition information will be 15 minutes different from the data of the biomarker in the tears, so after performing a time correction of 15 minutes, the physical condition information can be generated by performing additional conversion processing from the corrected data of the biomarker in the tears.

[0079] At this time, the conversion process may use, for example, an appropriate conversion formula, and more specifically, since the tear biomarker data that has undergone delay time correction and the actual body condition information have a very high correlation, a linear equation may be applied.

[0080] For example, as shown in the above figure 5, it is confirmed that the concentration value of tear sugar (data of biomarkers in tears) and the actual blood sugar concentration value have a high correlation, so the converted blood sugar value (physical condition information) can be expressed by the following equation 1.

[0081] Equation 1

[0082]

[0083] In the above equation 1, Y is blood sugar concentration, which is body condition information, T is time, and T L represents the delay time, and X represents the concentration of the collected tear biomarker data in the tear. In this case, using the delay time and the above-described Equation 1, a converted blood glucose value based on the collected tear glucose concentration can be generated and provided.

[0084] FIG. 9 is a diagram illustrating a management application of a biomarker measurement system using a smart contact lens according to one embodiment of the present invention.

[0085] As shown in the above figure 9, the analysis unit (33) can provide the generated body condition information to the terminal screen display unit in real time.

[0086] At this time, the delay time may vary significantly from person to person, but since the difference is small within a single individual, a consistent delay time can be applied to each individual. The delay time can range from 5 to 18 minutes, but since it cannot be set uniformly, it must be specified for each individual.

[0087] For example, the terminal (30) may include a delay time input unit (34) capable of inputting a delay time between a biomarker in the subject's tears and body condition information, as illustrated in FIG. 9. Accordingly, as described above, body condition information can be generated and provided based on the delay time by the analysis unit (33).

[0088] In addition, a conversion formula input unit (35) capable of inputting a conversion formula may be further included. Accordingly, as described above, body condition information can be generated and provided based on the delay time and conversion formula by the analysis unit (33).

[0089] For example, after visiting a hospital or similar location and wearing smart contact lenses, one could allow time for stabilization, measure tear glucose levels using the smart contact lenses, and simultaneously measure actual blood glucose levels using a standard blood glucose meter. By comparing the data measured simultaneously in this manner, the subject's delay time and conversion formula can be derived, which can then be input into the delay time input unit (34) and conversion formula input unit (35) of the management terminal (30), respectively.

[0090] According to the aforementioned embodiments of the present invention, a method for measuring biomarkers in tears using a smart contact lens can accurately measure chemical elements in tears by eliminating errors caused by reflected tears by introducing a stabilization time. In particular, since the concentration of chemical elements in only basic tears, which are highly correlated with blood, can be measured, the measurement accuracy is significantly increased.

[0091] In addition, in a system for measuring biomarkers in tears using smart contact lenses, the concept of delay time can be introduced to compensate for the delay in biomarker data in tears compared to actual blood body condition data.

[0092] The foregoing description of the present invention is for illustrative purposes only, and those skilled in the art will readily appreciate that the present invention can be readily modified into other specific forms without altering the technical spirit or essential characteristics of the present invention. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive. For example, each component described as a single entity may be implemented in a distributed manner, and similarly, components described as distributed may be implemented in a combined manner.

[0093] The scope of the present invention is indicated by the claims described below, and all changes or modifications derived from the meaning and scope of the claims and their equivalent concepts should be interpreted as being included in the scope of the present invention.

[0094] 10: Smart contact lenses

[0095] 20: Application

[0096] 30: Terminal

[0097] 31: Control unit

[0098] 32: Notification Department

[0099] 33: Analysis Department

[0100] 34: Delay time input section

[0101] 35: Conversion formula input section

Claims

1. A smart contact lens that is worn on the subject's eye to measure biomarkers in tears; and A terminal equipped with an application for collecting data of biomarkers in tears from the smart contact lens; A biomarker measurement system using a smart contact lens, characterized in that the terminal includes a control unit that controls the measurement of the biomarker in the tear after a stabilization time has passed since the smart contact lens was worn on the eye of the subject.

2. In paragraph 1, A biomarker measurement system using a smart contact lens, characterized in that the stabilization time is a predetermined time for the first tear layer present at the time of wearing the smart contact lens to return to a state suitable for measuring the biomarker in the tear, and is 1 minute or longer.

3. In paragraph 1, A biomarker measurement system using a smart contact lens, characterized in that the biomarker in the tear is at least one selected from the group consisting of Glucose, MMP-9, Lactoferrin, Cortisol, α-defensins, Cholesterol, and uric acid.

4. In paragraph 1, The above terminal, A biomarker measurement system using a smart contact lens, characterized in that it further includes a notification unit that provides a notification when the stabilization time is required.

5. In paragraph 1, The above terminal, A biomarker measurement system using a smart contact lens, characterized in that it further includes a notification unit that provides a notification when the stabilization time is required.

6. In paragraph 5, The terminal further includes a delay time input unit capable of inputting a delay time between the biomarker in the tears and the body condition information. A biomarker measurement system using a smart contact lens, characterized in that the analysis unit generates the body condition information based on the delay time input to the delay time input unit.

7. In paragraph 6, The above terminal further includes a conversion formula input section capable of inputting a conversion formula; A biomarker measurement system using a smart contact lens, characterized in that the analysis unit generates the body condition information based on the delay time input into the delay time input unit and the conversion formula input into the conversion formula input unit.

8. A method for measuring biomarkers in tears using smart contact lenses, When the smart contact lens is worn on the subject's eye, a step of controlling it to take a stabilization time; and A method for measuring a biomarker using a smart contact lens, characterized by including a step of measuring a biomarker in tears using the smart contact lens.

9. In paragraph 8, A method for measuring biomarkers using smart contact lenses, characterized in that the stabilization time is a predetermined time for the first tear layer present at the time of wearing the smart contact lenses to return to a state suitable for measuring biomarkers in the tears, and is 1 minute or longer.

10. In paragraph 8, A method for measuring biomarkers using a smart contact lens, characterized in that the biomarkers in the tears are at least one selected from the group consisting of Glucose, MMP-9, Lactoferrin, Cortisol, α-defensins, Cholesterol, and uric acid.

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