Doc Code: TR.PROV
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`Document Description: Provisional Cover Sheet (5816)
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`PTO/SB/16 (11-08)
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`U.S. Patent and Trademark Office: U.S. DEPARTMENT OF COMMERCE
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`Provisional Application for Patent Cover Sheet
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`This is a request for filing a PROVISIONAL APPLICATION FOR PATENT under 37 CFR 1.53(c)
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`lnventor(s)
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`Inventor 1
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`Given Name
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`Middle Name Family Name City
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`State
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`Remove
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`Country
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`Mohammed N.
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`Islam
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`Ann Arbor Ml
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`us
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`generated within this form by selecting the Add button.
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`I Add
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`NEAR-INFRARED LASERS FOR NON-INVASIVE MONITORING OF
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`GLUCOSE, KETONES, HBA1C, AND OTHER BLOOD CONSTITUENTS
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`Title of Invention
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`Attorney Docket Number (if applicable)
`OMNI0101PRV
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`Direct all correspondence to (select one):
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`® The address corresponding to Customer
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`Number 0 Firm or Individual Name
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`Customer Number
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`109543
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`The invention was made by an agency of the United States Government or under a contract with an agency of the United
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`States Government.
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`@) No.
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`Q Yes, the name of the U.S. Government agency and the Government contract number are:
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`EFS - Web 1.0.1
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`Petitioner Apple Inc. – Ex. 1016, cover p. 1
`
`

`

`Doc Code: TR.PROV
`Document Description: Provisional Cover Sheet (SB 16)
`
`PTO/SB/16 (11-08)
`Approved for use through 05/31/2015. OMB 0S51-OO32
`U.S. Patent and Trademark Office: U.S. DEPARTMENT OF COMMERCE
`Under the Paperwork Reduction Act of 1995, no persons are required to respond to a collection of information uniess it displays a valid OMB control number
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`Entity Status
`Applicant claims small entity status under 37 CFR 1.27
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`0 Yes, applicant qualifies for small entity status under 37 CFR 1.27
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`O No
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`Signature
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`Please see 37 CFR 1.4(d) for the form of the signature.
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`Signature
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`/David S. Bir/
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`First Name
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`David
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`Last Name
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`Bir
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`Date (YVVY-MM-DD)
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`2012-12-31
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`Registration Number
`(If appropriate)
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`38383
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`EPS - Web 1.0.1
`
`Petitioner Apple Inc. – Ex. 1016, cover p. 2
`
`

`

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`
`Petitioner Apple Inc. – Ex. 1016, cover p. 3
`
`

`

`OMNIOIOIPRV
`
`NEAR-INFRARED LASERS FOR NON-INVASIVE MONITORING OF GLUCOSE, KETONES,
`HBAIC, AND OTHER BLOOD CONSTITUENTS
`
`TECHNICAL FIELD
`
`[0001 ]
`
`This disclosure relates in general to lasers and light sources for healthcare, medical,
`
`or bio-technology applications including systems and methods for using near-infrared light sources
`
`for non-invasive monitoring of different blood constituents or blood analytes, such as glucose,
`
`ketones, and hemoglobin AlC (HbAlC).
`
`BACKGROUND AND SUMMARY
`
`[0002]
`With the growing obesity epidemic, the number of individuals with diabetes is also
`increasing dramatically. For example, there are over 200 million people who have diabetes.
`
`Diabetes control requires monitoring of the glucose level, and most glucose measuring systems
`
`available commercially require drawing of blood. Depending on the severity of the diabetes, a
`patient may have to draw blood and measure glucose four to six times a day. This may be extremely
`painful and inconvenient for many people. In addition, for some groups, such as soldiers in the
`battlefield, it may be dangerous to have to measure periodically their glucose level with finger
`
`pricks.
`
`Thus, there is an unmet need for non-invasive glucose monitoring (e.g., monitoring
`[0003]
`glucose without drawing blood). The challenge has been that a non-invasive system requires
`adequate sensitivity and selectivity, along with repeatability of the results. Yet, this is a very large
`
`market, with an estimated annual market of over $1 OB in 2011 for self-monitoring of glucose levels.
`
`[0004]
`One approach to non-invasive monitoring of blood constituents or blood analytes is to
`use near-infrared spectroscopy, such as absorption spectroscopy or near-infrared diffuse reflection or
`ti-ansmission spectroscopy. Some attempts have been made to use broadband light sources, such as
`tungsten lamps, to perform the spectroscopy. However, several challenges have arisen in these
`
`Petitioner Apple Inc. – Ex. 1016, p. 1
`
`

`

`OMNIOIOIPRV
`
`efforts. First, many other constituents in the blood also have signatures in the near-infrared, so
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`spectroscopy and pattern matching, often called spectral fingerprinting, is required to distinguish the
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`glucose with sufficient confidence. Second, the non-invasive procedures have often transmitted or
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`reflected light through the skin, but skin has many spectral artifacts in the near-infrared that may
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`mask the glucose signatures. Moreover, the skin may have significant water and blood content.
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`These difficulties become pailicularly complicated when a weak light source is used, such as a lamp.
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`More light intensity can help to increase the signal levels, and, hence, the signal-to-noise ratio.
`
`[0005]
`
`As described in this disclosure, by using brighter light sources, such as fiber-based
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`supercontinuum lasers, super-luminescent laser diodes, light-emitting diodes or a number of laser
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`diodes, the near-infrared signal level from blood constituents may be increased. By shining light
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`through the teeth, which have fewer spectral artifacts than skin in the near-infrared, the blood
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`constituents may be measured with less interfering artifacts. Also, by using pattern matching in
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`spectral fingei*printing and various software techniques, the signatures from different constituents in
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`the blood may be identified. Moreover, value-add services may be provided by wirelessly
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`communicating the monitored data to a handheld device such as a smart phone, and then wirelessly
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`communicating the processed data to the cloud for storing, processing, and transmitting to several
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`locations.
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`
`[0006]
`
`For a more complete understanding of the present disclosure, and for further features
`
`and advantages thereof, reference is now made to the following description taken in conjunction
`
`with the accompanying drawings, in which;
`
`[0007]
`
`FIGURE 1 plots the transmittance versus wavenumber for glucose in the mid-wave
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`and long-wave infrared wavelengths between approximately 2.7 to 12 microns.
`
`[0008]
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`FIGURE 2 illustrates measurements of the absorbance of different blood constituents,
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`such as glucose, hemoglobin, and hemoglobin Ale. The measurements are done using an FTIR
`
`spectrometer in samples with a 1mm path length.
`
`Petitioner Apple Inc. – Ex. 1016, p. 2
`
`

`

`OMNIOIOIPRV
`
`[0009]
`
`FIGURE 3A shows the normalized absorbance of water and glucose (not drawn to
`
`scale). Water shows transmission windows between about 1500-1850nm and 2050-2500nm.
`
`[0010]
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`FIGURE 3B illustrates the absorbance of hemoglobin and oxygenated hemoglobin
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`overlapped with water.
`
`[0011]
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`FIGURE 4A shows measured absorbance in different concentrations of glucose
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`solution over the wavelength range of about 2000 to 2400nm. This data is collected using a SWIR
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`super-continuum laser with the sample path length of about 1.1mm.
`
`[0012]
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`FIGURE 4B illustrates measured absorbance in different concentrations of glucose
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`solution over the wavelength range of about 1550 to ISOOnm. The data is collected using a SWIR
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`super-continuum laser with a sample path length of about 10mm.
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`[0013]
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`FIGURE 5 illustrates the spectrum for different blood constituents in the wavelength
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`range of about 2 to 2.45 microns (2000 to 2450nm).
`
`[0014]
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`FIGURE 6 shows the transmittance versus wavelength in microns for the ketone 3-
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`hydroxybutyrate. The wavelength range is approximately 2 to 16 microns.
`
`[0015]
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`FIGURE 7 illustrates the optical absorbance for ketones as well as some other blood
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`constituents in the wavelength range of about 2100 to 2400nm.
`
`[0016]
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`FIGURE 8A shows the first derivative spectra of ketone and protein at concentrations
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`of lOg/L (left). In addition, the first derivative spectra of urea, creatinine, and glucose are shown on
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`the right at concentrations of lOg/L.
`
`[0017]
`
`FIGURE 8B illustrates the near infrared absorbance for triglyceride.
`
`[0018]
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`FIGURE 8C shows the near-infrared reflectance spectmm for cholesterol.
`
`[0019]
`
`FIGURE 8D illustrates the near-infrared reflectance versus wavelength for various
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`blood constituents, including cholesterol, glucose, albumin, uric acid, and urea.
`
`Petitioner Apple Inc. – Ex. 1016, p. 3
`
`

`

`OMNIOIOIPRV
`
`[0020]
`
`FIGURE 9 shows a schematic of the human skin. In particular, the dermis may
`
`comprise significant amounts of collagen, elastin, lipids, and water.
`
`[0021]
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`FIGURE 10 illustrates the absorption coefficients for water (including scattering),
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`adipose, collagen, and elastin.
`
`[0022]
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`FIGURE 11 shows the dorsal of the hand, where a differential measurement may be
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`made to at least partially compensate for or subtract out the skin interference.
`
`[0023]
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`FIGURE 12 shows the dorsal of the foot, where a differential measurement may be
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`made to at least partially compensate for or subtract out the skin interference.
`
`[0024]
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`FIGURE 13 illustrates a typical human nail tissue structure and the capillary vessels
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`below it.
`
`[0025]
`
`FIGURE 14 shows the attenuation coefficient for seven nail samples that are allowed
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`to stand in an environment with a humidity level of 14%. These coefficients are measured using an
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`FTIR spectrometer over the near-infrared wavelength range of approximately 1 to 2.5 microns.
`
`Below is also included the spectmm of glucose.
`
`[0026]
`
`FIGURE 15 illustrates the structure of a tooth.
`
`[0027]
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`FIGURE 16A shows the attenuation coefficient for dental enamel and water versus
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`wavelength from approximately 600nm to 2600nm.
`
`[0028]
`
`FIGURE 16B illustrates the absorption spectrum of intact enamel and dentine in the
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`wavelength range of approximately 1.2 to 2.4 microns.
`
`FIGURE 17 shows the near infrared spectral reflectance over the wavelength range of
`[0029]
`approximately 800nm to 2500nm from an occlusal tooth surface. The black diamonds correspond to
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`the reflectance from a sound, intact tooth section. The asterisks correspond to a tooth section with
`
`an enamel lesion. The circles correspond to a tooth section with a dentine lesion.
`
`Petitioner Apple Inc. – Ex. 1016, p. 4
`
`

`

`OMNIOIOIPRV
`
`[0030]
`
`FIGURE ISA illustrates a clamp design of a human interface to cap over one or more
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`teeth and perform a non-invasive measurement of blood constituents.
`
`[0031]
`
`FIGURE 18B shows a mouth guai-d design of a human interface to perform a non-
`
`invasive measurement of blood constituents.
`
`[0032]
`
`FIGURE 19 illustrates a block diagram or building blocks for constructing high
`
`power laser diode assemblies.
`
`[0033]
`
`FIGURE 20 shows a platform architecture for different wavelength ranges for an all-
`
`fiber-integrated, high powered, super-continuum light source.
`
`[0034]
`
`FIGURE 21 illustrates one embodiment of a short-wave infrared (SWIR) super-
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`continuum (SC) light source.
`
`[0035]
`
`FIGURE 22 shows the output spectrum from the SWIR SC laser of FIGURE 21 when
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`~10m length of fiber for SC generation is used. This fiber is a single-mode, non-dispersion shifted
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`fiber that is optimized for operation near 1550nm.
`
`[0036]
`
`FIGURE 23 illustrates high power SWIR-SC lasers that may generate light between
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`approximately 1.4-1.8 microns (top) or approximately 2-2.5 microns (bottom).
`
`[0037]
`
`FIGURE 24 schematically shows that the medical measurement device can be part of
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`a personal or body area network that communicates with another device (e.g., smart phone or tablet)
`
`that communicates with the cloud. The cloud may in turn communicate information with the user,
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`healthcare providers, or other designated recipients.
`
`DETAILED DESCRIPTION
`
`[0038]
`
`As required, detailed embodiments of the present disclosure are disclosed herein;
`
`however, it is to be understood that the disclosed embodiments are merely exemplary of the
`
`disclosure that may be embodied in various and alternative forms. The figures are not necessarily to
`
`scale; some features may be exaggerated or minimized to show details of particular components.
`
`Petitioner Apple Inc. – Ex. 1016, p. 5
`
`

`

`OMNIOIOIPRV
`
`Therefore, specific structural and functional details disclosed herein are not to be interpreted as
`
`limiting, but merely as a representative basis for teaching one skilled in the art to variously employ
`
`the present disclosure.
`
`[0039]
`
`Various ailments or diseases may require measurement of the concentration of one or
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`more blood constituents. For example, diabetes may require measurement of the blood glucose and
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`HbAlc levels. On the other hand, diseases or disorders characterized by impaired glucose
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`metabolism may require the measurement of ketone bodies in the blood. Examples of impaired
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`glucose metabolism diseases include Alzheimer's, Parkinson's, Huntington's, and Lou Gehrig's or
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`amyotrophic lateral sclerosis (ALS). Techniques related to near-infrared spectroscopy or hyper-
`
`spectral imaging may be particularly advantageous for non-invasive monitoring of some of these
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`blood constituents.
`
`[0040]
`
`As used throughout this document, the term "couple" and or "coupled" refers to any
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`direct or indirect communication between two or more elements, whether or not those elements are
`
`physically connected to one another. As used throughout this disclosure, the term "spectroscopy"
`
`means that a tissue or sample is inspected by comparing different features, such as wavelength (or
`
`frequency), spatial location, ti'ansmission, absorption, reflectivity, scattering, refractive index, or
`
`opacity. In one embodiment, "spectroscopy" may mean that the wavelength of the light source is
`
`varied, and the transmission, absorption or reflectivity of the tissue or sample is measured as a
`
`function of wavelength. In another embodiment, "spectroscopy" may mean that the wavelength
`
`dependence of the transmission, absorption or reflectivity is compared between different spatial
`
`locations on a tissue or sample. As an illustration, the "spectroscopy" may be peifoimed by varying
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`the wavelength of the light source, or by using a broadband light source and analyzing the signal
`
`using a spectrometer, wavemeter, or optical spectrum analyzer.
`
`[0041]
`
`As used throughout this document, the term "fiber laser" refers to a laser or oscillator
`
`that has as an output light or an optical beam, wherein at least a part of the laser comprises an optical
`
`fiber. For instance, the fiber in the "fiber la.ser" may comprise one of or a combination of a single
`
`mode fiber, a multi-mode fiber, a mid-infrared fiber, a photonic crystal fiber, a doped fiber, a gain
`
`fiber, or, more generally, an approximately cylindrically shaped waveguide or light-pipe. In one
`
`Petitioner Apple Inc. – Ex. 1016, p. 6
`
`

`

`OMNIOIOIPRV
`
`embodiment, the gain fiber may be doped with rare earth material, such as ytterbium, erbium, and/or
`
`thulium. In another embodiment, the mid-infrared fiber may comprise one or a combination of
`
`fluoride fiber, ZBLAN fiber, chalcogenide fiber, tellurite fiber, or germanium doped fiber. In yet
`
`another embodiment, the single mode fiber may include standard single-mode fiber, dispersion
`
`shifted fiber, non-zero dispersion shifted fiber, high-nonlinearity fiber, and small core size fibers.
`
`[0042]
`
`As used throughout this disclosure, the term "pump laser" refers to a laser or
`
`oscillator that has as an output light or an optical beam, wherein the output light or optical beam is
`
`coupled to a gain medium to excite the gain medium, which in turn may amplify another input
`
`optical signal or beam. In one particular example, the gain medium may be a doped fiber, such as a
`
`fiber doped with ytterbium, erbium or thulium. In one embodiment, the "pump laser" may be a fiber
`
`laser, a solid state laser, a laser involving a nonlinear crystal, an optical parametric oscillator, a
`
`semiconductor laser, or a plurality of semiconductor lasers that may be multiplexed together. In
`
`another embodiment, the "pump laser" may be coupled to the gain medium by using a fiber coupler,
`
`a dichroic mirror, a multiplexer, a wavelength division multiplexer, a grating, or a fused fiber
`
`coupler.
`
`[0043]
`
`As used throughout this document, the term "super-continuum" and or
`
`"supercontinuum" and or "SC" refers to a broadband light beam or output that comprises a plurality
`
`of wavelengths. In a particular example, the plurality of wavelengths may be adjacent to one-
`
`another, so that the spectrum of the light beam or output appears as a continuous band when
`
`measured with a spectrometer. In one embodiment, the broadband light beam may have a bandwidth
`
`of at least lOnm. In another embodiment, the "super-continuum" may be generated through
`
`nonlinear optical interactions in a medium, such as an optical fiber or nonlinear crystal. For
`
`example, the "super-continuum" may be generated through one or a combination of nonlinear
`
`activities such as four-wave mixing, the Raman effect, modulational instability, and self-phase
`
`modulation.
`
`[0044]
`
`As used throughout this disclosure, the terms "optical light" and or "optical beam"
`
`and or "light beam" refer to photons or light transmitted to a particular location in space. The
`
`"optical light" and or "optical beam" and or "light beam" may be modulated or unmodulated, which
`
`Petitioner Apple Inc. – Ex. 1016, p. 7
`
`

`

`OMNIOIOIPRV
`
`also means that they may or may not contain information. In one embodiment, the "optical light"
`
`and or "optical beam" and or "light beam" may originate from a fiber, a fiber laser, a laser, a light
`
`emitting diode, a lamp, a pump laser, or a light source.
`
`SPECTRUM FOR GLUCOSE
`
`[0045]
`
`One molecule of interest is glucose. The glucose molecule has the chemical formula
`
`C6H12O6, so it has a number of hydro-carbon bonds. An example of the infrared transmittance of
`
`glucose 100 is illustrated in FIGURE 1. The vibrational spectroscopy shows that the strongest lines
`
`for bending and stretching modes of C-H and 0-H bonds lie in the wavelength range of
`
`approximately 6-12 microns. However, light sources and detectors are more difficult in the mid-
`
`wave infrared and long-wave infrared, and there is also strongly increasing water absorption in the
`
`human body beyond about 2.5 microns. Although weaker, there are also non-linear combinations of
`
`stretching and bending modes between about 2 to 2.5 microns, and first overtone of C-H stretching
`
`modes between approximately 1.5-1.8 microns. These signatures may fall in valleys of water
`
`absorption, permitting non-invasive detection through the body. In addition, there are yet weaker
`
`features from the second overtones and higher-order combinations between about 0.8-1.2 microns; in
`
`addition to being weaker, these features may also be masked by absorption in the hemoglobin.
`
`Hence, the short-wave infrared (SWIR) wavelength range of approximately 1.4 to 2.5 microns may
`
`be an attractive window for near-infrared spectroscopy of blood constituents.
`
`[0046]
`
`As an example, measurements of the optical absorbance 200 of hemoglobin, glucose
`
`and HbAlc have been performed using a Fourier-Transform Infrared Spectrometer - FTIR. As
`
`FIGURE 2 shows, in the SWIR wavelength range hemoglobin is nearly flat in spectrum 201 (the
`
`noise at the edges is due to the weaker light signal in the measurements). On the other hand, the
`
`glucose absorbance 202 has at least five distinct peaks near 1587nm, 1750nm, 2120nm, 2270nm and
`
`2320nm.
`
`[0047]
`
`FIGURE 3A overlaps 300 the normalized absorbance of glucose 301 with the
`
`absorbance of water 302 (not drawn to scale). It may be seen that water has an absorbance feature
`
`between approximately 1850nm and 2050nm, but water 302 also has a nice transmission window
`
`8
`
`Petitioner Apple Inc. – Ex. 1016, p. 8
`
`

`

`OMNIOIOIPRV
`
`between approximately ]500-1850nm and 2050 to 2500nm. For wavelengths less than about
`
`1 lOOnm, the absorption of hemoglobin 351 and oxygenated hemoglobin 352 in FIGURE 3B has a
`
`number of features 350, which may make it more difficult to measure blood constituents. Also,
`
`beyond 2500nm the water absorption becomes considerably stronger over a wide wavelength range.
`
`Therefore, an advantageous window for measuring glucose and other blood constituents may be in
`
`the SWIR between 1500 and 1850nm and 2050 to 2500nm. These are exemplary wavelength
`
`ranges, and other ranges can be used that would still fall within the scope of this disclosure.
`
`[0048]
`
`One further consideration in choosing the laser wavelength is known as the "eye safe"
`
`window for wavelengths longer than about 1400nm. In particular, wavelengths in the eye safe
`
`window may not transmit down to the retina of the eye, and therefore, these wavelengths may be less
`
`likely to create permanent eye damage. The near-infrared wavelengths have the potential to be
`
`dangerous, because the eye cannot see the wavelengths (as it can in the visible), yet they can
`
`penetrate and cause damage to the eye. Even if a practitioner is not looking directly at the laser
`
`beam, the practitioner's eyes may receive stray light from a reflection or scattering from some
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`surface. Hence, it can always be a good practice to use eye protection when working around lasers.
`
`Since wavelengths longer than about 1400nm are substantially not transmitted to the retina or
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`substantially absorbed in the retina, this wavelength range is known as the eye safe window. For
`
`wavelengths longer than 1400nm, in general only the cornea of the eye may receive or absorb the
`
`light radiation.
`
`[0049]
`
`Beyond measuring blood constituents such as glucose using FTIR spectrometers,
`
`measurements have also been conducted in another embodiment using super-continuum lasers,
`
`which will be described later in this disclosure. In this particular embodiment, some of the
`
`exemplary preliminary data for glucose absorbance are illustrated in FIGURES 4A and 4B. The
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`optical spectra 401 in FIGURE 4A for different levels of glucose concentration in the wavelength
`
`range between 2000 and 2400nm show the three absorption peaks near 2120nm (2.12pm), 2270nm
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`(2.27pm) and 2320nm (2.32pm). Moreover, the optical spectra 402 in FIGURE 4B for different
`
`levels of glucose concentration in the wavelength range between 1500 and 1800nm show the two
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`broader absorption peaks near 1587nm and 1750nm. It should be appreciated that although data
`
`Petitioner Apple Inc. – Ex. 1016, p. 9
`
`

`

`OMNIOIOIPRV
`
`measured with FTIR spectrometers or super-continuum lasers have been illustrated, other light
`
`sources can also be used to obtain the data, such as super-luminescent laser diodes, light emitting
`
`diodes, a plurality of laser diodes, or even bright lamp sources that generate adequate light in the
`
`SWIR.
`
`[0050]
`
`Although glucose has a distinctive signature in the SWIR wavelength range, one
`
`problem of non-invasive glucose monitoring is that many other blood constituents also have hydro
`
`carbon bonds. Consequently, there can be interfering signals from other constituents in the blood.
`
`As an example, FIGURE 5 illustrates the spectrum 500 for different blood constituents in the
`
`wavelength range of 2 to 2.45 microns. The glucose absorption spectrum 501 can be unique with its
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`three peaks in this wavelength range. However, other blood constituents such as triacetin 502,
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`ascorbate 503, lactate 504, alanine 505, urea 506, and BSA 507 also have spectral features in this
`
`wavelength range. To distinguish the glucose 501 from these overlapping spectra, it may be
`
`advantageous to have information at multiple wavelengths. In addition, it may be advantageous to
`
`use pattern matching algorithms and other software and mathematical methods to identify the blood
`
`constituents of interest. In one embodiment, the spectrum may be correlated with a library of known
`
`spectra to determine the overlap integrals, and a threshold function may be used to quantify the
`
`concentration of different constituents. This is just one way to perform the signal processing, and
`
`many other techniques, algorithms, and software may be used and would fall within the scope of this
`
`disclosure.
`
`KETONE BODIES MONITORING
`
`[0051]
`
`Beyond glucose, there are many other blood constituents that may also be of interest
`
`for health or disease monitoring. In another embodiment, it may be desirous to monitor the level of
`
`ketone bodies in the blood stream. Ketone bodies are three water-soluble compounds that are
`
`produced as by-products when fatty acids are broken down for energy in the liver. Two of the three
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`ai'e used as a source of energy in the heart and brain, while the third is a waste product excreted from
`
`the body. In particular, the three endogenous ketone bodies are acetone, acetoacetic acid, and beta-
`
`hydroxybutyrate or 3-hydroxybutyrate, and the waste product ketone body is acetone.
`
`10
`
`Petitioner Apple Inc. – Ex. 1016, p. 10
`
`

`

`OMNIOIOIPRV
`
`[0052]
`
`Ketone bodies may be used for energy, where they are transported from the liver to
`
`other tissues. The brain may utilize ketone bodies when sufficient glucose is not available for
`
`energy. For instance, this may occur during fasting, strenuous exercise, low carbohydrate, ketogenic
`
`diet and in neonates. Unlike most other tissues that have additional energy sources such as fatty
`
`acids during periods of low blood glucose, the brain cannot break down fatty acids and relies instead
`
`on ketones. In one embodiment, these ketone bodies are detected.
`
`[0053]
`
`Ketone bodies may also be used for reducing or eliminating symptoms of diseases or
`
`disorders characterized by impaired glucose metabolism. For example, diseases associated with
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`reduced neuronal metabolism of glucose include Parkinson's disease, Alzheimer's disease,
`
`amyotrophic lateral sclerosis (ALS, also called Lou Gehrig's disease), Huntington's disease and
`
`epilepsy. In one embodiment, monitoring of alternate sources of ketone bodies that may be
`
`administered orally as a dietary supplement or in a nutritional composition to counteract some of the
`
`glucose metabolism impairments is performed. However, if ketone bodies supplements are
`
`provided, there is also a need to monitor the ketone level in the blood stream. For instance, if
`
`elevated levels of ketone bodies are present in the body, this may lead to ketosis; hyperketonemia is
`
`also an elevated level of ketone bodies in the blood. In addition, both acetoace