United States Patent [19J
`Trebino et al.
`
`I 1111111111111111 11111 111111111111111 IIIII IIIII IIIII 11111 111111111111111111
`5,774,213
`Jun.30, 1998
`
`US005774213A
`[11] Patent Number:
`[45] Date of Patent:
`
`[54] TECHNIQUES FOR MEASURING
`DIFFERENCE OF AN OPTICAL PROPERTY
`AT TWO WAVELENGTHS BY MODULATING
`TWO SOURCES TO HAVE OPPOSITE(cid:173)
`PHASE COMPONENTS AT A COMMON
`FREQUENCY
`
`[76]
`
`Inventors: Rick P. Trebino, 425 Mulqueeney Dr.,
`Livermore, Calif. 94550; Nicholas M.
`Sampas, 806 Fremont St., Menlo Park,
`Calif. 94025; Eric K. Gustafson, 835
`Webster St., Apt. E, Palo Alto, Calif.
`94301
`
`[21] Appl. No.: 518,427
`
`[22] Filed:
`
`Aug. 23, 1995
`
`[63]
`
`[51]
`[52]
`[58]
`
`[56]
`
`Related U.S. Application Data
`
`Continuation-in-part of Ser. No. 426,790, Apr. 21, 1995,
`abandoned.
`Int. Cl.6
`..................................................... GOIN 21/31
`U.S. Cl. ............................. 356/320; 356/41; 356/408
`Field of Search .............................. 356/41, 321, 408,
`356/320
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`
`2,601,182
`3,332,313
`3,472,594
`3,647,299
`3,799,672
`4,183,669
`4,305,659
`4,350,441
`4,529,308
`4,948,248
`5,028,787
`
`6/1952 Tyler ....................................... 356/321
`7/1967 Batson .................................... 356/408
`10/1969 Hughes et al. .......................... 356/320
`3/1972 Lavallee .................................... 356/41
`3/1974 Yurek ........................................ 356/41
`1/1980 Doyle ...................................... 356/346
`12/1981 Bilstad et al.
`............................ 356/40
`9/1982 Wicnienski ......................... 356/408 X
`7/1985 Rife ......................................... 356/323
`8/1990 Lehman ................................ 356/41 X
`7/1991 Rosenthal et al. ...................... 250/341
`
`5,059,027
`5,137,023
`5,184,193
`5,206,701
`5,245,406
`5,251,008
`5,349,952
`
`10/1991 Roesler et al. .......................... 356/346
`8/1992 Mendelson et al. .................... 128/633
`2/1993 Lefebre .................................. 356/319
`4/1993 Taylor et al.
`........................... 356/325
`9/1993 Masutani ................................. 356/346
`10/1993 Masutani ................................. 356/346
`9/1994 Carthy et al. ......................... 356/41 X
`
`OTHER PUBLICATIONS
`
`Kelleher, Joseph F., "Pulse Oximetry," Little, Brown and
`Co., 1989, pp. 37-62.
`
`Primary Examiner-Vincent P. McGraw
`Attorney, Agent, or Firm-Townsend and Townsend and
`Crew LLP
`
`[57]
`
`ABSTRACT
`
`A technique for making precise spectrophotometric mea(cid:173)
`surements illuminates a sample with two or more modulated
`light sources at two or more, typically closely spaced,
`wavelengths. Light from the sources is combined,
`homogenized, and directed to the sample, and the light from
`the sample is collected and detected by a photodetector. The
`optical output powers of two sources are modulated with the
`same periodicity and with a reversed amplitude. Variations
`in the concentrations of species in the sample affect the
`modulation amplitude representing the sum of the optical
`powers from two sources in such a way as to produce an
`output signal. That output signal, based on an electrical
`component varying with a periodicity at the fundamental
`frequency, provides a measure of the difference in the
`transmissions ( or other optical properties) of the sample at
`the two wavelengths. Feedback methods, such as null-point
`detection, provide stable, sensitive measurements.
`Wavelength-division multiplexing-required for simulta(cid:173)
`neous measurements at many wavelengths-is achieved by
`modulating different pairs of sources at different frequen(cid:173)
`cies.
`
`11 Claims, 11 Drawing Sheets
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`Petitioner Apple Inc. – Ex. 1049, p. 1
`
`

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`U.S. Patent
`
`Jun.30, 1998
`
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`Petitioner Apple Inc. – Ex. 1049, p. 2
`
`

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`U.S. Patent
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`Jun.30, 1998
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`Petitioner Apple Inc. – Ex. 1049, p. 3
`
`

`

`U.S. Patent
`
`Jun.30, 1998
`
`Sheet 3 of 11
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`5,774,213
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`Petitioner Apple Inc. – Ex. 1049, p. 4
`
`

`

`U.S. Patent
`
`Jun.30, 1998
`
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`Petitioner Apple Inc. – Ex. 1049, p. 5
`
`

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`U.S. Patent
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`Jun.30, 1998
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`Petitioner Apple Inc. – Ex. 1049, p. 6
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`

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`U.S. Patent
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`Jun.30, 1998
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`Petitioner Apple Inc. – Ex. 1049, p. 7
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`

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`U.S. Patent
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`Jun.30, 1998
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`Petitioner Apple Inc. – Ex. 1049, p. 8
`
`

`

`U.S. Patent
`US. Patent
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`Jun.30, 1998
`Jun. 30, 1998
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`Petitioner Apple Inc. — EX. 1049, p. 9
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`Petitioner Apple Inc. – Ex. 1049, p. 9
`
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`Petitioner Apple Inc. – Ex. 1049, p. 10
`
`

`

`U.S. Patent
`US. Patent
`
`Jun.30, 1998
`Jun. 30, 1998
`
`Sheet 10 of 11
`Sheet 10 0f 11
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`5,774,213
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`Petitioner Apple Inc. — Ex. 1049, p. 11
`
`Petitioner Apple Inc. – Ex. 1049, p. 11
`
`

`

`U.S. Patent
`US. Patent
`
`Jun.30, 1998
`Jun. 30, 1998
`
`Sheet 11 0f 11
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`5,774,213
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`Petitioner Apple Inc. — Ex. 1049, p. 12
`
`Petitioner Apple Inc. – Ex. 1049, p. 12
`
`

`

`5,774,213
`
`1
`TECHNIQUES FOR MEASURING
`DIFFERENCE OF AN OPTICAL PROPERTY
`AT TWO WAVELENGTHS BY MODULATING
`TWO SOURCES TO HAVE OPPOSITE(cid:173)
`PHASE COMPONENTS AT A COMMON
`FREQUENCY
`CROSS-REFERENCE TO RELATED
`APPLICATION
`This application is a continuation-in-part of U.S. appli(cid:173)
`cation Ser. No. 08/426,790, filed Apr. 21, 1995, now
`abandoned, which application is incorporated herein by
`reference for all purposes.
`BACKGROUND OF THE INVENTION
`The present invention relates generally to optical
`spectroscopy, and more specifically to a spectrophotometer
`suitable for performing non-invasive measurement of meta(cid:173)
`bolic analytes and for determining characteristics of sub(cid:173)
`stances in the solid, liquid, and gas phases in other, e.g.
`industrial settings.
`A new generation of medical and industrial diagnostic
`instruments based upon optical spectroscopy, typically in the
`near infrared region, enable non-invasive measurements of
`metabolic constituents in the body and of a wide range of
`parameters of inanimate objects and fluids. These diagnostic
`techniques involve measuring the absorbance, scatter,
`transmission, or reflection spectra of living tissue non(cid:173)
`invasively, and hence conveniently and painlessly. Already,
`optical diagnostics exist or are under active development for
`measuring a wide variety of important metabolic quantities,
`including oxygen saturation of hemoglobin, body fat,
`cholesterol, triglycerides, bilirubin, and glucose. In addition,
`similar optical diagnostic techniques are important in
`agriculture, semiconductor processing, petroleum process(cid:173)
`ing and refining, combustion diagnostics and other fields.
`To extract information relating to metabolic analyte con(cid:173)
`centrations or material properties from raw spectral
`measurements, one uses any one of a variety of inversion
`techniques. A specific theoretical or empirical model may be
`known. More commonly, one uses a technique known as
`chemometric-multivariate calibration, or "chemometrics"
`Chemometrics is a class of sophisticated mathematical algo(cid:173)
`rithms that reduce large spectral calibration matrices to a
`mathematical model that can be applied to new spectral data
`to determine the concentrations of various constituent ana(cid:173)
`lytes. Commonly used chemometric algorithms include:
`partial least squares (PLS), multiple linear regression
`(MLR), and principal component regression (PCR). In
`addition, another method involves the use of neural net(cid:173)
`works. This latter method is especially useful when nonlin(cid:173)
`ear behavior occurs, and the linearity assumption of chemo(cid:173)
`metrics is no longer valid.
`For all but a few simple diagnostics, extremely sensitive
`measurements are required for reasonably reliable measure(cid:173)
`ments. This is especially the case, in the example of in vivo
`glucose measurement where the absorbance changes due to
`glucose are weak. Unfortunately, devices with sufficient
`sensitivities for measurement of these analytes are prohibi(cid:173)
`tively expensive (typically exceeding $30,000). As a result,
`diabetics stand little chance of home glucose monitoring
`with a non-invasive optical device with existing technology.
`In general, when many species contribute to the absorption
`signal, high sensitivity is required. Indeed, the greater the
`sensitivity of the spectrophotometer, the more species may
`be measured, and, in particular, trace species or very weakly
`absorbing species may be measured.
`
`2
`Currently available spectrophotometers fall into two gen(cid:173)
`eral classes, (1) those designed for general optical spectros(cid:173)
`copy and (2) those designed specifically for non-invasive
`clinical applications. The devices in the first class include
`5 both Fourier-transform spectrometers (FTS's) and
`frequency-domain grating-tuned spectrophotometers
`(GTS's). Both these types of instruments are engineered for
`maximal sensitivity and high resolution, and hence they are
`quite costly. An FTS involves a highly sensitive, precisely
`10 aligned optical interferometer, the optical pathlength of
`which is scanned during a measurement. It also requires a
`powerful computer that can rapidly calculate fast Fourier
`transforms (FFT's). Because of their complexity, FTS's are
`likely to remain expensive. GTS's are also finely tuned
`15 instruments with high resolution determined by precisely
`scanning (to less than a microradian) a finely ruled diffrac(cid:173)
`tion grating. As a result, high-resolution GTS's will
`undoubtedly remain expensive as well. In addition, due to
`their need for precise alignment, both of these devices tend
`20 to be heavy and not portable.
`The second class of spectrophotometers, which will be
`referred to as "portable" spectrophotometers, offer only
`limited spectral resolution and hence typically only involve
`measurements at a modest number of wavelengths. See, for
`25 example, U.S. Pat. No. 5,028,787 to Rosenthal et al. Such
`devices are useful for specific diagnostic analyses, generally
`of a solid or liquid-phase sample, in which only low reso(cid:173)
`lution is required, and typically, the number of required
`wavelengths is limited and often known in advance. These
`30 devices typically require less than ½oooth the resolution of
`the general-spectroscopic class of spectrophotometers.
`Indeed, simple portable devices that measure the most
`strongly absorbing quantities in tissue, such as the oxidation
`of hemoglobin, require as few as two wavelength measure-
`35 ments and are in fact inexpensive. See, for example, J. F.
`Kelleher, "Pulse Oximetry," J. Clinical Monitoring, Vol. 5,
`#1, pp. 37-62 (1989). More commonly, industrial measure(cid:173)
`ments and human body analyte diagnostics require between
`10 and 40 wavelengths to provide sufficient information due
`40 to the many interfering absorptions of other species in the
`range of physiological or industrial interest. In addition,
`such measurements are possible only when the signals are
`relatively strong and the number of competing species is
`limited. Most important clinical and industrial problems,
`45 however, involve much more weakly absorbing substances.
`As a result, significantly higher sensitivity is also required.
`Current portable spectrophotometers have not only very
`low resolution, but also very low sensitivity. There are a
`variety of reasons for this. One is the common use of pulsed
`50 sources, which are substantially noisier than continuous(cid:173)
`wave sources. Another is the use of sequential measure(cid:173)
`ments of the absorbances at the various wavelengths of
`interest, thus allowing drift to introduce error into the
`measured spectrum. In addition, no attempt is made to take
`55 advantage of clever noise-reduction techniques used in other
`fields (such as null-point detection). Often devices analo(cid:173)
`gous to available high-resolution devices are used, and
`hence tend to be both expensive and heavy. The state of art
`in noise reduction in grating-type spectrophotometers is
`60 nicely reviewed in U.S. Pat. No. 5,206,701 to Taylor et al.
`Many applications also require real-time monitoring of
`the spectral properties of a sample. Unfortunately, standard
`methods are too slow to achieve rapid measurements
`because they involve slowly scanning the wavelength (as in
`65 GTS's and in devices in which the many sources are
`sequentially pulsed) or scanning an optical delay path (as in
`FTS's). These devices, are therefore too slow for many
`
`Petitioner Apple Inc. – Ex. 1049, p. 13
`
`

`

`5,774,213
`
`4
`quantization error in the digitization. If, for example, an
`analog-to-digital converter (ADC) has 14 bits ( that is, about
`0.01 % accuracy) and the difference between the transmis(cid:173)
`sions at neighboring wavelengths is about 0.01 %, then the
`error in the derivative measurements is on the order of
`100%. Measurements of the second derivative are even more
`problematic, and, in this example, would be meaningless.
`An array of next-generation medical and industrial diag(cid:173)
`nostics applications will become possible as greater sensi(cid:173)
`tivity and more stable and more precise spectrophotometers
`become feasible and economical. Many other fields, such as
`process control and environmental safety, will benefit, as
`well.
`
`5
`
`3
`real-time monitoring applications, which involve temporally
`resolving, for example, changes in blood volume due to the
`heart pulse. In addition, most spectrophotometers make DC
`measurements. DC measurements integrate noise at low
`frequencies, and hence are extremely sensitive to low-
`frequency or "1/f" noise.
`The most common problem with spectrophotometers is
`that spectra tend to vary from measurement to measurement
`due to drifts associated with the sources, electronics, and
`detector within the instrument. Specifically, two spectra 10
`taken only seconds apart in an unchanging medium may
`have similar spectral characteristics, but are typically offset
`somewhat relative to each other. Consequently, one spec(cid:173)
`trum will appear slightly more (or less) absorbing than
`another at all wavelengths. Similarly, there often occur slow 15
`baseline shifts across a single spectrum. Uncorrected, the
`use of such baseline-shifted spectra generally yields erro(cid:173)
`neous or poor quality results. Such instrument drifts there(cid:173)
`fore limit sensitivity and hence the diagnostic power of the
`technique. The only devices for which source drift is not a 20
`serious limitation are FTS's, but, as mentioned, their
`alignment-sensitivity, weight, and high cost make them
`unsuitable for small-scale medical, clinical, quality-control,
`or regulatory applications.
`To minimize this problem, it is common practice to
`subtract the intensity of a reference beam that takes an
`independent path that does not involve passing through the
`sample. This method is discussed in U.S. Pat. No. 5,206,701
`to Taylor et al., U.S. Pat. No. 5,184,193 to LeFebre, and U.S.
`Pat. No. 4,529,308 to Rife. U.S. Pat. No. 4,183,669 to Doyle
`discusses the use of a reference beam in a Fourier-transform
`spectrophotometer. The use of a reference beam in this
`manner is helpful but it still does not solve the problem of
`different drifts in the components of the two different light
`paths.
`An additional method that addresses the latter problem is
`the normalization of the spectrum by subtracting off the
`absolute transmission value at some reference wavelength.
`Unfortunately, this approach is limited because drift can
`occur in the time interval between the desired measurement
`and the reference measurement. A better method, one also
`commonly used, is to compute the first or second derivative
`of a spectrum with respect to wavelength before using it to
`determine a useful value of the desired quantity. In this way,
`consecutive measurements are subtracted, and reliance on a
`single reference measurement for the entire spectrum is not
`necessary.
`Taking the first derivative subtracts off any constant
`background, and taking the second derivative subtracts off a
`linearly sloped background. Typically, the useful informa(cid:173)
`tion contained in a spectrum is unaffected by these
`transformations, but the noise associated with the individual
`wavelength measurements increases with each higher order
`of derivative. This is because the derivative is a difference
`between approximately equal adjacent spectral values, and
`each time such a difference is computed, the noise increases
`significantly. It would be much better to somehow measure
`the first or second derivative directly as a single
`measurement, and not as a difference between two measure(cid:173)
`ments ( as in the first derivative) or worse, as a difference of
`differences ( as in the second derivative).
`Most commonly, however, the derivative spectra are
`computed, and not measured directly: the transmissions
`measured at all wavelengths are digitized, and the differ- 65
`ences are computed digitally. Unfortunately, this method has
`limited sensitivity due to noise in each measurement and the
`
`SUMMARY OF IBE INVENTION
`The present invention provides a technique for making
`precise spectrophotometric measurements suitable for use in
`connection with non-invasive monitoring of human meta(cid:173)
`bolic analytes and industrial products. The invention
`achieves low cost and very high sensitivity while allowing
`the extraction of nearly drift-free derivative spectra using
`only a single detector. Derivative measurements are made at
`all wavelengths simultaneously and without the need to
`compute a difference.
`Broadly, the invention contemplates illuminating a
`25 sample with two or more independently modulated light
`sources at two or more, typically closely spaced, wave(cid:173)
`lengths. Light from the sources is combined, homogenized,
`and directed to the sample, and the light from the sample is
`collected and detected by a photodetector. The light from the
`30 sample may be reflected, transmitted, or scattered. The
`optical output powers of two sources, typically adjacent in
`wavelength, are modulated with the same periodicity and
`with a reversed amplitude (opposite sign) so as to have a
`common frequency component at an electrical frequency,
`35 but with opposite-phase AC intensity components for the
`two sources.
`Variations in the concentrations of species in the sample
`affect the modulation amplitude representing the sum of the
`optical powers from two sources in such a way as to produce
`40 an output signal. That output signal, based on an electrical
`component varying with a periodicity at the fundamental
`frequency, provides a measure of the difference in the
`transmissions ( or other optical properties) of the sample at
`the two wavelengths. From one such two-wavelength mea-
`45 surement the relative concentration of one species can be
`measured (in the absence of interfering species). In
`principle, each additional wavelength allows one additional
`species to be measured.
`Thus, the invention recognizes that medical and industrial
`50 diagnostics require high sensitivity but typically without the
`requirement of high resolution (since solid- and liquid-phase
`absorptions are inherently spectrally broad). In view of this,
`the invention is able to combine a number of techniques that
`have previously been regarded as inappropriate in the con-
`55 text of spectrophotometers. These techniques, which include
`instantaneous background subtraction and derivative
`measurement, phase-sensitive detection, null-point detec(cid:173)
`tion and frequency-division multiplexing, provide low-cost,
`high-sensitivity, low-noise, low-drift spectral measure-
`60 ments.
`A further understanding of the nature and advantages of
`the present invention may be realized by reference to the
`remaining portions of the specification and the drawings.
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`FIG. 1 is a schematic of an embodiment of the invention
`using two sources and no feedback;
`
`Petitioner Apple Inc. – Ex. 1049, p. 14
`
`

`

`5,774,213
`
`5
`FIG. 2A shows plots of optical power at the two wave(cid:173)
`lengths and the total optical power before the light encoun(cid:173)
`ters the sample;
`FIG. 2B shows plots of optical power at the two wave(cid:173)
`lengths and the total optical power after the light encounters 5
`the sample;
`FIG. 3 is a schematic of an embodiment of the invention,
`which uses negative feedback to equalize the optical power
`of the two sources;
`FIG. 4 is a schematic of an embodiment which uses
`negative feedback to null the residual modulation of the light
`from the sample;
`FIG. 5 is a schematic of an embodiment which switches
`the negative feedback between the regimes shown in FIGS. 15
`3 and 4;
`FIG. 6 is a schematic of an embodiment corresponding to
`that of FIG. 4, extended to provide N difference measure(cid:173)
`ments through the use of 2N sources;
`FIG. 7 is a schematic of an embodiment corresponding to
`that of FIG. 4, extended to provide N difference measure(cid:173)
`ments through the use of (N+l) sources;
`FIG. 8 is a schematic of an embodiment corresponding to
`that of FIG. 3, extended to provide N difference measure(cid:173)
`ments through the use of (N+l) sources;
`FIG. 9 is a schematic of a multi-wavelength embodiment
`with feedback utilizing a digital-signal-processor (DSP)
`chip ( or other microprocessor) to perform all functions,
`including chemometrics, digitally; and
`FIG. 10 is a schematic of an alternative tunable light
`source utilizing a graded interference filter which makes the
`two-wavelength null-point technique work as a first deriva(cid:173)
`tive spectrometer.
`
`6
`The light from the homogenizer encounters the sample,
`and is detected by a photodetector 30. The photodetector
`transforms optical power to an electrical signal (voltage or
`current), which is amplified by a preamplifier 40.
`Amplitude modulation of the sources is effected by an
`oscillator 45, having a fundamental frequency Q, typically
`in the range from 1 kHz to 1 MHz. The oscillator drives
`source 20a with a modulation of one phase and drives source
`20b through an inverting amplifier 47 to provide modulation
`10 with the opposite phase. The waveforms representing each
`of the signals are shown schematically along their respective
`signal lines. The two sources are driven with respective
`average powers, P 1 and P 2 and modulation powers li.P 1 and
`li.P 2 . The power of source 20a is P 1-li.P 1 cos(Qt) while that
`of source 20b is P2 +li.P2 cos(Qt)), whereupon the total
`power is
`
`P,0 ,-P,+P2.(IIJ'2-IIJ'1) cos(Qt)
`In this embodiment, the average powers and modulation
`20 powers are adjusted such that li.P 1 =li.P 2 , so that P tot shows no
`modulation at the fundamental frequency. Similarly, the total
`power incident on the sample shows no modulation at the
`fundamental frequency. This is shown in FIG. 2A.
`To the extent that the sample transmits both wavelengths
`25 of light equally, the light incident on the photodetector will
`not be modulated at the fundamental frequency. However, if,
`as shown in FIG. 2B, the sample transmits differently at the
`two wavelengths, the light incident on the photodetector will
`be modulated at the fundamental frequency in an amount
`30 proportional to the difference in the transmissions at the two
`wavelengths. Let T(} .. 1) be the transmission of the medium at
`A1 and T(A2) be the transmission of the medium at A2 . The
`transmitted power Ptottrans will then be:
`
`DESCRIPTION OF SPECIFIC EMBODIMENTS
`
`35
`
`Two-Wavelength Embodiment without Feedback
`FIG. 1 is an optical and electrical schematic of a system
`10 according to a first embodiment of the invention. The
`purpose of the system is to determine the difference in the 40
`transmission ( or other optical property) of light at two
`wavelengths on encountering a sample, shown as a human
`finger 15.
`Light at the two wavelengths is provided by first and
`second amplitude modulated sources 20a and 20b, which in 45
`the specific embodiment are light-emitting diodes (LEDs).
`Light from LEDs 20a and 20b is directed through respective
`lenses 22a and 22b and through respective filters 25a and
`25b to a beam homogenizer 27. The combination of sources,
`filters, and lenses can be considered a source assembly 28. 50
`The need for filters depends on the bandwidth of the
`sources and the wavelength separation of the two sources. In
`some embodiments, a typical wavelength spacing is on the
`order of 5-10 nm. Since LEDs typically have a bandwidth
`on the order of 20 nm, the filters should have respective 55
`bandpass widths on the order of 5-10 nm. Laser diodes may
`also be used, and, due to their narrower bandwidth (say less
`than 0.1 nm), would not need to be used in conjunction with
`filters. It would be necessary to choose the proper laser diode
`wavelengths. There may be some applications where the 60
`wavelengths are sufficiently separated that filters are not
`necessary, even if LEDs are used.
`LEDs that operate at room temperature are available in
`the visible and near infrared ranges, most commonly in the
`600---1000 nm range and at wavelengths of 1300 nm and 65
`1550 nm, the latter two wavelengths being in wide use in
`fiber optic communication systems.
`
`prans
`'°'
`
`T(A1) (Pi - IIJ' cos (Qt))+ T(}..z) (P2 + IIJ' cos (Qt))
`
`T(A1)P1 + T(A2)P2 + IIJ'(}..z - A1)T("j;_) cos (Qt)
`
`where li.P is the common value of the modulation power
`(since li.P 1 =li.P 2 , the subscript is dropped) and the transmis(cid:173)
`sion spectral derivative, T'(A), is
`
`T(}..z) - T(A1)
`
`T("j;_) - --,._~2---,._-1--
`
`where Xis the average of A1 and A2 . Note that the modulated
`term (i.e., the term proportional to cos(Qt)) is proportional
`to the desired quantity, the spectral derivative, T'(X), and the
`other factors in this term are easily measured. The extent of
`the modulation therefore provides a measure of the desired
`transmission difference. In addition, the phase of the modu(cid:173)
`lation of the transmitted light provides the sign of transmis(cid:173)
`sion differences, which can be positive or negative.
`Note that if A2 and A1 are nearby wavelengths (that is, the
`spectrum does not change significantly between A1 and A2),
`the quantity T'(X) will accurately indicate the transmission
`derivative. If the spectrum does change significantly
`between A1 and A2 , the method is still valid; one is simply
`not measuring the derivative. The noise-reduction features
`continue to operate, but the derivative interpretation no
`longer applies.
`An output signal representing this difference (T'(A)) is
`generated using phase-sensitive detection. Specifically, the
`signal from preamplifier 40 is filtered by a bandpass filter 50
`and mixed at a mixer 52 with a local oscillator signal derived
`from oscillator 45. The phase of the local oscillator signal is
`adjusted by a phase adjuster 55. Filter 50 suppresses all
`
`Petitioner Apple Inc. – Ex. 1049, p. 15
`
`

`

`5,774,213
`
`7
`frequency components in the photodetector signal except the
`one at the fundamental, Q, which is converted to DC by
`mixer 52. This output signal is measured and constitutes a
`point in the derivative spectrum.
`In order that useful information be derived from the 5
`voltage output signal of mixer 52, the signal may be output
`to a meter or converted to digital form by an analog-to(cid:173)
`digital converter 57 and communicated to a processor 58 for
`further processing. In various embodiments described
`below, the meter or analog-to-digital converter and proces- 10
`sor will not be illustrated, but it is to be understood that they
`will typically be present.
`
`8
`tion. This error signal is used to impose a difference in the
`modulated intensities of the two sources in a manner tending
`to null out the fundamental component in the detector signal.
`In particular, the output from mixer 52 is communicated to
`servo amplifier 80, whose output is communicated to the
`gain adjustment input of inverting amplifier 62. The output
`from the servo amplifier now represents the desired trans(cid:173)
`mission difference of the sample at the two source wave(cid:173)
`lengths.
`This technique is referred to as "null-point detection," and
`it is in the most sensitive instruments ever developed, the
`class of scanned-probe microscopes (see H. K.
`Wickramasinghe, Scientific American Oct. '89 p.98) which
`are capable of spatial resolution on the order of an angstrom.
`
`Feedback switching between Before Sample and
`After Sample
`FIG. 5 is an optical and electrical schematic of a system
`120 according to an embodiment in the error signal is
`alternately switched by a switch 122 between one signal
`derived from the light detected directly (as in FIG. 3) and
`anot