WO2025096929A1

WO2025096929A1 - Wavelength switching phototherapy device

Info

Publication number: WO2025096929A1
Application number: PCT/US2024/054102
Authority: WO
Inventors: Peter Broer; Alan Greszler
Original assignee: Lumitex Inc
Current assignee: Lumitex Inc
Priority date: 2023-11-02
Filing date: 2024-11-01
Publication date: 2025-05-08
Anticipated expiration: 2026-05-02

Abstract

A phototherapy system is provided for treating neonatal jaundice in an infant by controlling phototherapy based on properties of the infant. The system includes processor circuitry for altering control variables received by a light source based on sensor measurements of bilirubin levels, skin tone, or hematocrit levels.

Description

WAVELENGTH SWITCHING PHOTOTHERAPY DEVICE Related Applications This application claims the benefit of US 63/595,434 filed on November 2, 2023. Which is herein incorporated by reference in its entirety. Technical Field The present disclosure relates generally to phototherapy and more particularly to selecting treatment parameters for phototherapy. Summary Phototherapy is a common and effective treatment for neonatal jaundice, a condition where a newborn has high levels of bilirubin in the blood. The key principle behind phototherapy is to use light to transform bilirubin into isomers that are more water-soluble and can be excreted by the infant's body without the need for further metabolism by the liver. The wavelength of light used in phototherapy determines effectiveness of the treatment. The most effective wavelength range for converting bilirubin is between 430 and 490 nanometers, which falls within the blue-green spectrum. This range is effective because it corresponds to the absorption peak of bilirubin. The present disclosure provides a phototherapy system for treating neonatal jaundice in an infant by controlling phototherapy based on properties of the infant such that the infant receives a therapeutic effect. While a number of features are described herein with respect to embodiments of the invention; features described with respect to a given embodiment also may be employed in connection with other embodiments. The following description and the annexed drawings set forth certain illustrative embodiments of the invention. These embodiments are indicative, however, of but a few of the various ways in which the principles of the invention may be employed. Other objects, advantages and novel features according to aspects of the invention will become apparent from the following detailed description when considered in conjunction with the drawings. Brief Description of the Drawings The annexed drawings, which are not necessarily to scale, show various aspects of the invention in which similar reference numerals are used to indicate the same or similar parts in the various views. FIG. 1 is a block diagram of a phototherapy system. FIG. 2 is an exemplary graph showing absorbance of light by red blood cells. FIG. 3 is an exemplary graph showing absorbance of light by melanin and bilirubin. FIG. 4 is an exemplary graph showing the relationship between a center wavelength of the light emitted by the light source of FIG. 1 and hematocrit level as a sensed parameter. FIG. 5 is an exemplary graph showing the relationship between a center wavelength of the light emitted by the light source of FIG. 1 and hematocrit level as a sensed parameter. The present invention is described below in detail with reference to the drawings. In the drawings, each element with a reference number is similar to other elements with the same reference number independent of any letter designation following the reference number. In the text, a reference number with a specific letter designation following the reference number refers to the specific element with the number and letter designation and a reference number without a specific letter designation refers to all elements with the same reference number independent of any letter designation following the reference number in the drawings. Detailed Description The present disclosure provides a phototherapy system for treating neonatal jaundice in an infant by controlling phototherapy based on properties of the infant. The system includes processor circuitry for altering control variables received by a light source based on sensor measurements of bilirubin levels, skin tone, or hematocrit levels. Turning to FIG. 1, a phototherapy system 10 is shown for treating neonatal jaundice in an infant by controlling phototherapy based on properties of the infant. The phototherapy system 10 controls the phototherapy such that the infant 11 receives a therapeutic effect. The phototherapy system includes a light source 12, processor circuitry 14, and a sensor 16. The light source 12 emits light 18 (within a wavelength range) for illuminating the infant. The light source 12 modifies properties of the emitted light based on control variables 20 received from the processor circuitry 14. The processor circuitry 14 alters the control variables 20 received by the light source to modify properties of the emitted light 20 based on sensed parameters 22 output by the sensor 16. The sensor 16 measures as sensed parameters 22 at least one of bilirubin levels in the infant, skin tone of the infant, or hematocrit levels of the infant. The processor circuitry 14 uses the sensed parameters 22 to modify at least one of the wavelength, intensity, timing, or duration of illumination of the light 18. In this way, the processor circuitry 14 alters the control variables 20 based on the sensed parameters 22 such that the wavelength range of the emitted light 18 is optimized to reduce the bilirubin levels of the infant. The rationale behind the wavelength shifting executed by the processor circuitry 14 may be to identify and utilize a wavelength for phototherapy that is most optimal for the specific infant under treatment. This wavelength adjustment can be effected by manipulating the wavelengths of light emitted by the light source or through the deployment of optical filters, such as band-pass filters. The wavelength range of the emitted light 18 may include a center wavelength and a band of wavelengths around the center wavelength. For example, the band may have a 20 nm width, such that a majority of the emitted light is within plus or minus 10 nm of the center wavelength. The wavelength range may be within 430-490 nm. As an example, the center wavelength may be changed from 440 nm (a band of 430-450 nm) to 480 nm (a band of 470- 490 nm). The most effective wavelength range for converting bilirubin is between 430 and 490 nm. In this spectrum, at the lower end near 430 nm, absorption by red blood cells is significant (see FIG. 2). As the wavelength increases towards the middle of this range (around 450-460 nm, which is the peak absorption for bilirubin), the absorption by red blood cells decreases slightly. Towards the higher end of the range (approaching 490 nm), the absorption by red blood cells continues to decrease. Given the relationship between hematocrit levels and light absorption, the processor circuitry may be configured (as is described in further detail below) to shift the wavelength of the emitted light from nearer 450 nm to closer to 490 nm (such as approximately 480 nm) allowing for more effective phototherapy at higher hematocrit levels. Similarly, as shown in FIG. 3, melanin’s absorption of light decreases towards the higher end of the range (i.e., approaching 490 nm). Consequently (as is described in further detail below), in cases of infants with darker skin tones (i.e., having a higher melanin content), the processor circuitry 14 may increase the wavelength of emitted light 18 to increase a portion of the emitted light that has a therapeutic effect (i.e., reducing an amount of non-therapeutic light). An exemplary relationship between center wavelength of the emitted light and skin tone (increasing melanin content to the right) is shown in FIG. 4. The adjustment of the center wavelength by the processor circuitry 14 in response to increasing skin tone or hematocrit levels can follow various mathematical relationships, depending on the desired therapeutic outcome and empirical data. For example, the change in center wavelength may be directly proportional to the measured parameter, resulting in a linear relationship. In this case, as the skin tone darkens or hematocrit levels increase, the center wavelength λc is adjusted upward in a consistent, predictable manner, calculated using the equation: λ_c = λ₀ + k × S where: • λ0 is the base center wavelength (e.g., 450 nm), • k is a proportionality constant determined empirically, • S represents the quantified skin tone or hematocrit level. Alternatively, the processor circuitry 14 may employ a non-linear relationship, such as exponential or logarithmic, to adjust the center wavelength more precisely based on how the absorption characteristics change with the measured parameters. For an exponential relationship, the adjustment may be calculated as: λc = λ0 × e^k×S In this scenario, small increases in skin tone or hematocrit levels could result in larger shifts in the center wavelength, which may be beneficial if absorption by melanin or hemoglobin significantly impacts the therapeutic efficacy at certain levels. A logarithmic relationship may also be used, particularly if the effect of skin tone or hematocrit levels on light absorption diminishes at higher values:

By selecting the appropriate mathematical model and calibrating the constants k based on clinical studies and empirical data, the phototherapy system 10 may fine-tune the center wavelength to optimize phototherapy for each individual infant. The light source and processor circuitry are not limited to causing the light source to emit light within the 430-490 nm wavelength range, but may include additional wavelength ranges. For example, green light (e.g., around 520 nm) may also be used for treating jaundice. As described above, the processor circuitry 14 determines the control variables 20 based on the sensed parameters 22 (also referred to as sensor measurements) received from the sensor 16. The sensor 16 may include at least one of a bilirubin sensor for measuring the bilirubin levels of the infant, a hematocrit sensor for measuring the hematocrit levels of the infant, or a photosensor for measuring the skin tone of the infant. As is described in further detail below, the sensed parameters 22 may be received directly or indirectly from a sensor. For example, the sensed parameters 22 may include blood test results that are input into the processor circuitry 14 by a user. With exemplary reference to FIG. 5, the sensed parameters 22 may include the hematocrit levels of the infant. The hematocrit levels may be determined via a blood test and a user may enter the blood test results into the phototherapy system 10. The processor circuitry 14 may alter the control variables 20 such that a center wavelength of the wavelength range increases with high hematocrit levels. As another example, the sensed parameters 22 may include the skin tone of the infant (e.g., received from a camera). The processor circuitry 14 may alter the control variables 20 such that a center wavelength of the wavelength range increases with darker skin tones. As another example, the sensed parameters 22 may include at least one of the hematocrit levels or the skin tone. The skin tone of the infant may be determined by user input or using a photosensor (such as a camera). The processor circuitry 14 may alter the control variables 20 based on the sensed parameters 22 by calculating as non-therapeutic light a portion of the emitted light that does not contribute to the therapeutic effect. For example, the skin tone may be used to estimate a percentage of the emitted light 18 that is absorbed by the skin as heat. Similarly, the hematocrit levels may be used to estimate a percentage of the emitted light 18 that is absorbed by red blood cells of the infant. To determine the skin tone of the infant, the sensor 16 may utilize a calibrated colorimetric camera or spectrophotometer integrated into the phototherapy system 10. The camera captures images of the infant's skin under standardized lighting conditions to minimize variability. The processor circuitry 14 may analyze these images to quantify the skin tone by measuring the reflectance or absorbance of specific wavelengths of light associated with melanin content. This quantification may involve comparing the measured values against a predefined skin tone scale, such as the Fitzpatrick skin type classification or the Individual Typology Angle (ITA) scale. The processor circuitry 14 may apply image processing algorithms to correct for any ambient lighting effects, ensuring accurate assessment of the skin tone. By converting the skin tone measurements into numerical values representing melanin concentration, the processor circuitry 14 can use this data to adjust the control variables 20 accordingly. The processor circuitry 14 may then alter the control variables 20 to compensate for the estimated non-therapeutic light. That is, higher hematocrit levels and darker skin tones may result in greater absorption of emitted light 18 that does not contribute to the reduction in bilirubin levels. For example, if the estimated non-therapeutic light is 20% (i.e., 20% of the emitted light does not contribute to a therapeutic effect), then the intensity or duration of phototherapy may be altered to increase the optical dosage by 20% to make up for the estimated non-therapeutic light. When the sensed parameters 22 include the hematocrit levels, the processor circuitry 14 may estimate as the non-therapeutic light a percentage of the emitted light 18 absorbed by the blood of the patient based on the hematocrit levels. Similarly, when the sensed parameters 22 include the skin tone, the processor circuitry may determine wavelength absorption properties of the skin of the infant based on the measured skin tone. The processor circuitry 14 may then determine an overlap of the wavelength range of the emitted light and the determined wavelength absorption properties of the skin. The processor circuitry 14 may use this information to estimate as the non-therapeutic light a percentage of the emitted light absorbed by the skin of the patient based on the determined overlap. The calculation of non-therapeutic light involves estimating the proportion of the emitted light 18 that is absorbed by the infant's skin and blood without contributing to the phototherapy's effectiveness in reducing bilirubin levels. For the skin absorption component, the processor circuitry 14 may use the quantified skin tone data to determine the melanin absorption coefficient at various wavelengths within the emitted light's range. This may be achieved by referencing established optical absorption spectra for melanin. The processor circuitry 14 may then calculates the skin's absorbance Askin(λ) at each wavelength λ using the formula:

where: • αmelanin(λ) is the wavelength-dependent absorption coefficient of melanin, • C_melanin is the concentration of melanin derived from the skin tone measurement, • d is the path length through the skin. For the blood absorption component, the processor circuitry 14 may estimate the absorption of light by hemoglobin in the blood based on the hematocrit levels. The hematocrit level provides the volume percentage of red blood cells in the blood, which correlates with the concentration of hemoglobin. The absorbance Ablood(λ) at each wavelength may be calculated using:

where: • αhemoglobin(λ) is the absorption coefficient of hemoglobin at wavelength λ\lambdaλ, • C_hemoglobin is the concentration of hemoglobin estimated from the hematocrit level, • d is the path length through the blood. The total non-therapeutic absorbance Atotal(λ) may be calculated as the sum of skin and blood absorbance: ^_^^^^^^^^ = ^_^^^^^^^ + ^_^^^^^^^^ The processor circuitry 14 may then calculate the percentage of non-therapeutic light absorbed using the Beer-Lambert law, which relates absorbance to transmittance:

Non-therapeutic light percentage=[1−T(λ)]×100% By integrating this percentage over the entire wavelength range of the emitted light 18, the processor circuitry 14 determines the overall proportion of non-therapeutic light. This calculation allows the processor circuitry 14 to adjust the control variables 20, such as increasing the intensity or shifting the wavelength range, to compensate for the loss of therapeutic efficacy due to absorption by the skin and blood. For instance, if a significant portion of the therapeutic wavelengths is absorbed non-therapeutically, the processor circuitry 14 may opt to emit light at wavelengths less absorbed by melanin or hemoglobin while still effective for bilirubin reduction. In another embodiment, the sensor 16 may include a photosensor for measuring the skin tone of the infant. The processor circuitry 14 may determine a change in jaundice level of the infant by receiving the skin tone as the sensed parameters 22 at two different time points. The processor circuitry 14 may then use this information to measure a change in a yellow content of the skin tone between the two different time points. The processor circuitry 14 may then adjust the control variables 20 based on the determined change in the jaundice level of the infant, such that a reduction in the jaundice level of the infant results in a decrease in an optical dose received by the infant over a duration of time. In a further embodiment, the sensor 16 may include a camera (e.g., a machine vision sensor) for determining an area of the infant illuminated during phototherapy. The processor circuitry 14 may use the output of the camera to determine an optical dose received by the infant per unit of time. That is, the processor circuitry 14 may receive the output of the camera and determine an area of the infant illuminated by the emitted light. The processor circuitry 14 may then determine an optical dose received by the infant based on the determined area of the infant illuminated. For example, the processor circuitry 14 may calculate an area (e.g., in cm²) illuminated by the camera and multiply this calculated area by the intensity of the emitted light and a time duration that the infant was illuminated by the light. The processor circuitry 14 may periodically calculate the area to take into account changes in the area illuminated (e.g., due to the infant moving) when calculating the optical dose received by the infant. The processor circuitry 14 may use this information to vary the intensity of the emitted light and a length/duration of time of the phototherapy session (i.e., how long the infant is illuminated with light). In one embodiment, the sensor 16 includes an identification sensor for detecting an identification band (e.g., an RFID wrist band) on the infant. The processor circuitry 14 may determine an amount of time the infant is located within an area illuminated by the emitted light based on the detection of the identification band. In another embodiment, the sensor 16 includes a transcutaneous bilirubin sensor for measuring the bilirubin levels of the infant (also referred to as transcutaneous bilirubin (TcB)). The processor circuitry 14 may receive the output of the transcutaneous bilirubin sensor and blood bilirubin levels measured using a blood test to calibrate the transcutaneous bilirubin sensor. The bilirubin sensor may continuously monitor bilirubin levels. The sensor 16 may also sense at least one of the skin tone or the hematocrit levels of the infant. The processor circuitry 14 may continuously alter the control variables 20 to affect an intensity and a center wavelength of the wavelength range of the emitted light based on the bilirubin levels and at least one of the skin tone or hematocrit levels. The processor circuitry may also alter an illumination schedule of the light source based on time of day. That is, the processor circuitry 14 may also alter the control variables 20 based on the time of day, such that the wavelength range and intensity of the emitted light 18 synchronizes with a circadian rhythm of the infant. For example, the control variables 20 may cause the emitted light 18 to include longer wavelengths in the wavelength range closer to sunset compared to midday. Similarly, the emitted light 18 may include shorter wavelengths in the wavelength range closer to sunrise compared to midday. Also, the emitted light 18 may have a higher intensity at midday compared to sunset. The processor circuitry 14 may modify the schedule of light illumination (i.e., when phototherapy is applied throughout the day). This feature may enable the adaptation of phototherapy sessions to align with hospital staffing schedules, allowing treatments to be administered over one or two shifts, as opposed to a more fragmented approach. To modify the schedule, the processor circuitry 14 may receive (1) a time duration corresponding to a shift schedule of medical personnel and (2) a desired optical dose. The processor circuitry 14 may alter the control variables 20 based on the received time duration and the received desired optical dose, such that the infant receives the desired optical dose of the emitted light within the time duration. The light source 12 may have various implementations. For example, the light source 12 may include any suitable device capable of emitting light within the desired wavelength range for phototherapy treatment, such as light-emitting diodes (LEDs), organic LEDs (OLEDs), laser diodes, fluorescent lamps, halogen lamps, fiber optic illuminators, or other suitable light-emitting components. The light source 12 may be designed to emit light with adjustable properties, including wavelength, intensity, timing, and duration of illumination, as controlled by the processor circuitry 14. It may incorporate optical elements such as lenses, filters, diffusers, reflectors, or collimators to shape and direct the emitted light toward the infant effectively. The light source 12 may also include driver circuits, power supplies, cooling systems, and other ancillary components necessary for its operation. Instructions for adjusting the light properties may be received from the processor circuitry 14, allowing for real-time modulation based on the sensed parameters. The light source 12 may be communicatively coupled to the processor circuitry 14 through wired connections like electrical conductors or circuit boards, or wirelessly using suitable communication protocols. It can be integrated into the phototherapy system as a built-in unit or configured as a modular component that can be replaced or upgraded as needed. The sensor 16 may have various implementations. For example, the sensor 16 may include any suitable device for measuring the sensed parameters, such as a photodetector, photodiode, phototransistor, spectrometer, colorimeter, camera, optical sensor, or other suitable sensing devices. The sensor 16 may be configured to detect at least one of the bilirubin levels in the infant, the skin tone of the infant, or the hematocrit levels of the infant. This may involve the use of transcutaneous bilirubin sensors, optical skin sensors, hematocrit sensors, or other suitable sensors known in the art. The sensor 16 may also include associated circuitry such as amplifiers, filters, analog-to-digital converters, or other signal conditioning components necessary to process the sensor signals for use by the processor circuitry 14. Additionally, the sensor 16 may be communicatively coupled to the processor circuitry 14, either directly or via suitable interfaces like a system bus or network interface, to transmit the sensed parameters for processing. The sensor 16 may be powered by the system's power supply or may have its own power source, such as a battery. It can be integrated into the phototherapy system or function as a separate device that communicates with the system either wirelessly or through wired connections. The processor circuitry 14 may have various implementations. For example, the processor circuitry 14 may include any suitable device, such as a processor (e.g., CPU), programmable circuit, integrated circuit, memory and I/O circuits, an application specific integrated circuit, microcontroller, complex programmable logic device, other programmable circuits, or the like. The processor circuitry 14 may also include a non-transitory computer readable medium, such as random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or Flash memory), or any other suitable medium. Instructions for performing the method described below may be stored in the non- transitory computer readable medium and executed by the processor circuitry 14. The processor circuitry 14 may be communicatively coupled to the computer readable medium and network interface through a system bus, mother board, or using any other suitable structure known in the art. All ranges and ratio limits disclosed in the specification and claims may be combined in any manner. Unless specifically stated otherwise, references to “a,” “an,” and/or “the” may include one or more than one, and that reference to an item in the singular may also include the item in the plural. Although the invention has been shown and described with respect to a certain embodiment or embodiments, equivalent alterations and modifications will occur to others skilled in the art upon the reading and understanding of this specification and the annexed drawings. In particular regard to the various functions performed by the above described elements (components, assemblies, devices, compositions, etc.), the terms (including a reference to a "means") used to describe such elements are intended to correspond, unless otherwise indicated, to any element which performs the specified function of the described element (i.e., that is functionally equivalent), even though not structurally equivalent to the disclosed structure which performs the function in the herein illustrated exemplary embodiment or embodiments of the invention. In addition, while a particular feature of the invention may have been described above with respect to only one or more of several illustrated embodiments, such feature may be combined with one or more other features of the other embodiments, as may be desired and advantageous for any given or particular application.

Claims

Claims 1. A phototherapy system for treating neonatal jaundice in an infant by controlling phototherapy based on properties of the infant such that the infant receives a therapeutic effect, the system comprising: a light source configured to emit light within a wavelength range for illuminating the infant; processor circuitry configured to modify properties of the light emitted by the light source by altering control variables received by the light source, wherein the modified properties of the emitted light include at least one of wavelength, intensity, timing, or duration of illumination; and a sensor configured to measure as sensed parameters at least one of bilirubin levels in the infant, skin tone of the infant, or hematocrit levels of the infant; wherein the processor circuitry is further configured to alter the control variables based on the sensed parameters such that the wavelength range of the emitted light is optimized to reduce the bilirubin levels of the infant. 2. The phototherapy system of claim 1, wherein the wavelength range includes a center wavelength and a band of wavelengths around the center wavelength. 3. The phototherapy system of claim 2, wherein the band has a 20 nm width, such that a majority of the emitted light is within plus or minus 10 nm of the center wavelength. 4. The phototherapy system of claim 2, wherein the wavelength range is within 430-490 nm. 5. The phototherapy system of claim 1, wherein the sensor is at least one of a bilirubin sensor for measuring the bilirubin levels of the infant, a hematocrit sensor for measuring the hematocrit levels of the infant, or a photosensor for measuring the skin tone of the infant. 6. The phototherapy system of claim 5, wherein: the sensed parameters include the hematocrit levels of the infant; the processor circuitry alters the control variables such that a center wavelength of the wavelength range increases with high hematocrit levels. 7. The phototherapy system of claim 5, wherein: the sensed parameters include the skin tone of the infant; the processor circuitry alters the control variables such that a center wavelength of the wavelength range increases with darker skin tones. 8. The phototherapy system of claim 5, wherein: the sensed parameters include at least one of the hematocrit levels or the skin tone; and the processor circuitry is configured to alter the control variables based on the sensed parameters by: calculating as non-therapeutic light a portion of the emitted light that does not contribute to the therapeutic effect by: when the sensed parameters include the hematocrit levels, estimating as the non-therapeutic light a percentage of the emitted light absorbed by a blood of the patient based on the hematocrit levels; and when the sensed parameters include the skin tone: determining wavelength absorption properties of a skin of the infant based on the measured skin tone; determining an overlap of the wavelength range of the emitted light and the determined wavelength absorption properties of the skin; estimating as the non-therapeutic light a percentage of the emitted light absorbed by the skin of the patient based on the determined overlap; and altering the control variables to compensate for the estimated non-therapeutic light. 9. The phototherapy system of claim 5, wherein the sensor includes a transcutaneous bilirubin sensor for measuring the bilirubin levels of the infant. 10. The phototherapy system of claim 1, wherein: the sensor includes a photosensor for measuring the skin tone of the infant; the processor circuitry is configured to: determine a change in jaundice level of the infant by: receiving the skin tone as the sensed parameters at two different time points; and measuring a change in a yellow content of the skin tone between the two different time points; adjust the control variables based on the determined change in the jaundice level of the infant, such that a reduction in the jaundice level of the infant results in a decrease in an optical dose received by the infant over a duration of time. 11. The phototherapy system of claim 1, wherein: the sensor includes a camera; the processor circuitry is further configured to: determine an area of the infant illuminated by the emitted light based on an output of the camera; and determine an optical dose received by the infant based on the determined area of the infant illuminated. 12. The phototherapy system of claim 1, wherein: the sensor includes an identification sensor configured to detect an identification band on the infant; the processor circuitry is further configured to determine an amount of time the infant is located within an area illuminated by the emitted light based on the detection of the identification band. 13. The phototherapy system of claim 1, wherein: the sensor is configured to continuously monitor bilirubin levels and at least one of the skin tone or the hematocrit levels; the processor circuitry is configured to continuously alter the control variables to affect an intensity and a center wavelength of the wavelength range of the emitted light based on the bilirubin levels and at least one of the skin tone or hematocrit levels. 14. The phototherapy system of claim 1, wherein the processor circuitry is configured to alter the control variables based on the time of day, such that the wavelength range and intensity of the emitted light synchronizes with a circadian rhythm of the infant by: including longer wavelengths in the wavelength range closer to sunset compared to midday; including shorter wavelengths in the wavelength range closer to sunrise compared to midday; and having a higher intensity at midday compared to sunset. 15. The phototherapy system of claim 1, wherein the processor circuitry is configured to: receive time duration corresponding to a shift schedule of medical personnel; receive a desired optical dose; and alter the control variables based on the received time duration and the received desired optical dose, such that the infant receives the desired optical dose of the emitted light within the time duration.