WO1999005961A1

WO1999005961A1 - Analyzing system with disposable calibration device

Info

Publication number: WO1999005961A1
Application number: PCT/US1998/015597
Authority: WO
Inventors: Jonathan A. Eppstein; Mark A. Samuels; Keith D. Ignotz; Gregory J. Newman; Robert Rothfritz; Scott Kerr; Glenn Steven Arche; Scott Kellogg; Shabbir Bambot; Richard Lachlan Fowler
Original assignee: Spectrx, Inc.
Priority date: 1997-08-01
Filing date: 1998-07-31
Publication date: 1999-02-11
Also published as: AU8666298A

Abstract

A system and method for calibrating a measurement instrument (3) prior to making a measurement on a material or tissue (40) includes utilizing a removable calibration device (45) to calibrate the instrument, then removing a target portion of the calibration device so that a measurement may be performed. The target portion of the calibration device may have reflective/scattering properties, transmissive properties, or fluorescent properties that are used by the instrument to perform a calibration operation. A method embodying the invention may include making a bilirubin concentration measurement on a skin of a patient by measuring the amplitude of light reflected from the patient's skin at first, and second wavelengths indicative of a blood content of the patient's skin; measuring the amplitude of reflected light at a third wavelength indicative of an uncorrected bilirubin concentration; and then calculating a corrected bilirubin concentration based on the three measurements.

Description

ANALYZING SYSTEM WITH DISPOSABLE CALIBRATION DEVICE

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to instruments that measure characteristics and/or

conditions of target materials or tissues, and in particular, to such instruments that

utilize a calibration device. The invention also relates to apparatus and methods of

determining a patient bilirubin concentration.

2. Background of the Related Art

There are a variety of measuring instruments that utilize light to detect

physical characteristics or conditions of a material. Some such instruments are used

by medical personnel to determine a condition of a patient. The use of light to

determine a characteristic or condition of a target material is generally called

spectroscopy. Spectroscopy has become more common in medical applications with

the development of appropriate and inexpensive light sources, detection devices and

optical fibers that allow for minimal invasiveness.

Typically, spectral reflectance, scattering, transmittance, fluorescence (normal

and time resolved) and Raman spectroscopy are used to evaluate materials in order

to determine the types of materials present and to measure their concentrations. One type of spectroscopy, reflectance spectroscopy, involves diffusely

reflecting light from a target material, and analyzing the reflected light. In another

type of spectroscopy, called transmittance spectroscopy, light passes through a target

material, and the transmitted light is analyzed. In other spectroscopic methods,

illuminating a target material may cause the target material to emit fluorescent or

luminescent light that can then be analyzed. In still other spectroscopic methods, a

target material may be illuminated with polarized light, and reflected or transmitted

light is analyzed to determine how the polarization of the light has changed. The

polarization change can be used to determine characteristics or conditions of the

target material.

An example of a spectroscopic measuring instrument is shown in Figure 3C.

The instrument 3 emits light, at one or more wavelengths, from a nose portion.

Light that is scattered or reflected from a target material 40, or light generated by the

target material, is then collected and analyzed by the instrument to determine a

characteristic or condition of the target material 40.

Spectroscopic instrument accuracy can be affected by variations in light source

intensity, spectral characteristics, lens-aging, lens cleanliness, temperature, detector

sensitivity changes, and electronic drifting. To correct for any potential measuring

inaccuracies, it is common to periodically calibrate a spectroscopic measuring

instrument. Calibration techniques usually involve conducting a measurement on

a test target having characteristics that remain stable over time and over a range of temperatures. The calibration techniques can be used to compensate for instrument

to instrument variations, and for any changes that an individual instrument may

experience over its working lifetime.

During a calibration operation, a spectroscopic measuring instrument is aimed

at a calibration target having known optical properties. Light is then scattered or

reflected by the calibration target, and received back in the instrument. Because the

calibration target has known optical properties, the instrument is able to perform a

calibration operation to ensure that the instrument continues to deliver accurate

results.

Also, some measuring instruments may use a reference target as part of a

measurement process. In such a device, the instrument is aimed at a reference target

having known optical properties. Light from the instrument is scattered or reflected

from the reference target, and a reading is taken. The results of the measurement

operation conducted on the reference target can then be used as a standard or

reference against which patient measurements are judged. For instance, the result of

a patient reading could be derived by determining a difference or ratio between a

patient reading and a reading taken on a reference target. Because the optical

properties of the reference target are known, variations in light output or detector

sensitivity can be accounted for by use of the reference target. Throughout the remainder of the application, including the claims, the terms

"calibration target" and "reference target" are used interchangeably. Any reference

to a calibration target is equally applicable to a reference target, and vice versa.

When a measuring instrument is used with human or animal patients, steps

must be taken to ensure that use of the instrument does not contaminate or infect the

patient. When the instrument is successively used to examine two different patients,

steps must be taken to ensure that there is no cross contamination between the

patients.

Although others have proposed calibration fixtures that compensate for the

above-described variations in instrument performance, none have provided a

simultaneous solution to both the calibration issue and the problems associated with

the spread of infection in a medical setting. Furthermore, calibration devices that are

designed to be re-used can become damaged by sunlight, temperature, humidity and

other effects, which could lead to errors in calibration.

One application of spectroscopic measurement systems involves detection of

a bilirubin concentration in a human. Bilirubin is produced from the breakdown of

hemoglobin in red blood cells. Under normal conditions, the bilirubin is conjugated

by glucoronyl transferase, an enzyme present in the liver, and is then excreted

through the biliary system.

Newborn infants and prematurely born infants are particularly susceptible to

hyperbihrubinemia. Hyperbihrubinemia describes the state where there is excessive bilirubin in the body. Often this is due to the lack of functioning glucoronyl

transferase enzyme in their liver, or excessive red blood cell breakdown associated

with erythroblastosis fetalis.

One method for bilirubin testing includes blood based lab assay testing. The

"heel stick" blood lab assay is currently the only accepted methodology for

quantitative bilirubin testing results in the United States. Of course, this invasive

approach requires that blood be drawn to perform the test.

Non-invasive measurements of the bilirubin concentration would eliminate

the need to draw blood samples from patients for bilirubin analysis. It would also

provide easy patient interface. It is known that bilirubin can be measured non-

invasively by taking reflectance measurements from a patient's skin, from the

aqueous of the eye, or from the sclera (white) of the eye, based on the fluorescent

signature. Reflectance measurements can also be made on the tympanic membrane

of the ear. This is possible because bilirubin from the blood stains the skin as well

as other tissues of the body. Jaundice refers to the condition when the bilirubin is

visible in the skin and sclera.

Many attempts have been made to measure cutaneous bilirubin non-invasively.

These attempts include the development of visual reference standards, and

transcutaneous reflectance spectroscopy to measure the absorption spectra of

bilirubin, oxidized blood, and melanin, the dominant absorbers in the skin. The

concentration of these pigments have distinct absorption spectra. Reflectance bilirubinometers have obtained reasonable correlations between

bilirubin levels determined transcutaneously and serum bilirubin concentrations in

homogeneous patient populations. Unfortunately, these devices have failed to give

satisfactory correlations when used over a heterogeneous population. Since patient

populations are rarely homogeneous, transcutaneous bilirubin measuring methods

have not been widely accepted clinically.

SUMMARY OF THE INVENTION

An object of the invention is to provide a measurement system with a

disposable calibration device that is inexpensive and that helps to prevent

contamination or infection.

Another object of the invention is to provide a spectroscopic system which

uses a calibration device which provides an optically clear, scratch-free window

between the optical instrument and the tissue or material to be measured.

It is also an object of the invention to provide a disposable calibration target

configured for single use only.

Another object of the invention is to provide a simple and accurate apparatus

and method of measuring a patient's bilirubin concentration.

A further object of the invention is to provide a system and method for

comparing the optical characteristics of a first target material to optical characteristics

of a second target material. A measuring instrument embodying the invention transmits radiation to a

material or tissue and receives and analyzes radiation transmitted through, reflected

from or scattered from, or generated by the material or tissue being measured. In

some embodiments, the radiation emitted by the instrument may be polarized, and

the polarization orientation of the transmitted, reflected/scattered or generated

radiation may be analyzed by the instrument. Also, particular embodiments of the

invention may combine multiple ones of the above listed techniques to arrive at a

diagnosis of a patient, or to provide an analysis of a target material.

A measuring instrument embodying the invention may include a spectrometer

capable of determining the amplitude of radiation at any of a plurality of

wavelengths. Alternatively, the measuring instrument may comprise a detector and

one or more filters for selectively focusing radiation of specified wavelengths upon

the detector. The measuring instrument could also comprise a plurality of filters and

a corresponding plurality of detectors, where radiation from a target material passes

through the filters and onto the detectors so that each detector receives radiation at

a different wavelength. The measuring instrument might also comprise a diffraction

grating and a plurality of detectors, wherein the diffraction grating focuses radiation

of predetermined wavelengths on respective ones of the plurality of detectors. Still

further, the radiation analyzer may comprise a radiation detector and a linear variable

filter. In still other embodiments of the invention, a measuring system could include

a plurality of emitter and detector pairs arranged in an array on the measuring

instrument. Light output from the emitters could reflect/scatter/transmit from a

target material or tissue or light could be emitted from the material or tissue, and the

light would be received by the corresponding detectors. In another embodiment,

the measuring system could include a single light source for illuminating a target

material or tissue, and an array of detectors, such as a charge coupled device (CCD),

for receiving light that is reflected/scattered/transmitted/emitted from the target

material or tissue. Each of these embodiments would allow the measuring

instrument to develop an image of the target material or tissue, or an image of

reflective/transmissive/fluorescent properties of the target material or tissue.

A measurement instrument embodying the invention also may include one or

more transmit and receive fiber optic waveguides for directing electromagnetic

radiation to a material or tissue to be measured and for conducting radiation from a

target material or tissue back to a sensor of the instrument. The instrument may be

configured such that radiation transmitted from the instrument toward the material

or tissue being measured is directed toward the material or tissue at an angle relative

to a plane normal to the surface of the material or tissue so as to reduce

backscattering effects.

A method and device embodying the invention may measure a bilirubin

concentration in a patient using the amplitude of radiation reflected from a patient's skin at first and second wavelengths representing a blood content of the skin, and at

a third wavelength representing an uncorrected bilirubin concentration. Such a

method and instrument may also utilize the amplitude of reflected radiation at fourth

and fifth wavelengths that represent a melanin content of the patient's skin.

A measuring instrument embodying the invention may include a calibration

device that includes a structure through which radiation can be transmitted. The

calibration device may also include a removable calibration target arranged on said

structure and capable of returning a portion of radiation output by the instrument

back to a sensor of the instrument for purposes of conducting a calibration operation.

In alternate embodiments, radiation may be transmitted through the calibration

target before passing to a sensor of the instrument. In still other embodiments, the

calibration target may include a fluorescent or luminescent portion that emits

fluorescent or luminescent radiation towards a sensor of the measuring instrument

for purposes of conducting a calibration operation. The removable calibration target

is configured to be removed from the structure of the calibration device after a

calibration operation is completed, while the structure remains attached to the

measuring instrument, so that radiation can pass through the structure during a

subsequent measuring operation.

When the instrument is for medical diagnostic purposes, a calibration device

embodying the invention may include a shield to prevent patient contamination or

infection. In some embodiments, the calibration device may comprise both an infection shield and a calibration or reference target with known optical properties

integrated into a single unitary element.

In preferred embodiments, the removable calibration target is configured such

that a portion of the calibration target having predetermined optical characteristics

is destructively altered when it is removed from a structure of the calibration device.

As will be explained more fully below, configuring the calibration device so that it

can only be used once can help to prevent patient infection or cross-contamination.

A calibration device embodying the invention may also include an index

matching substance, such as a gel, that can be interposed between a material or tissue

being measured and a distal end of a measurement instrument.

In one method embodying the invention, a reference target is attached to an

output end of a measuring instrument. A first measurement is then taken with a

light source of the measurement instrument turned off. This is called a dark

reference reading. Next, a measurement is taken on the reference target with the

ght source turned on. This is termed a reference reading. The reference target is

then removed from the measurement instrument, and a first measurement is

conducted on a patient or an object with the light source of the instrument turned

off. This is termed a dark object reading. Next, a patient or object measurement is

conducted with the light source turned on. This is termed an object reading. A ratio

is then created with a difference between the object reading and the dark object

reading in the numerator, and a difference between the reference reading and the dark reference reading being in the denominator. By creating a ratio of the differences,

any variation in the light output of the measurement instrument or of the detector

sensitivity cancels out to provide an accurate measurement result.

In addition, the reference reading, dark reference reading, skin reading and

dark skin reading can all be corrected for "stray light." The correction for stray light

also helps to ensure that the measurement reading is more accurate. A method and

formula for calculating and correcting for stray light is provided in the detailed

description below.

Additional advantages, objects, and features of the invention will be set forth

in part in the description which follows, and in part will become apparent to those

having ordinary skill in the art upon examination of the following, or may be learned

from practice of the invention. The objects and advantages of the invention may be

realized and attained as particularly pointed out in the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1A shows a schematic view of a measurement system in a calibration

mode;

Figure IB shows a measurement system in a measurement mode wherein a

calibration target has been removed and radiation is reaching a tissue or material to

be measured; Figure 2A shows a schematic representation of a calibration device embodying

the invention;

Figure 2B shows the calibration device of Figure 2A after a calibration target

is removed from a window of the device;

Figure 2C shows a schematic sectional representation of another calibration

device embodying the invention;

Figure 2D is a schematic representation of the calibration device of Figure 2C

after a removable seal has been removed;

Figure 2E shows a schematic representation of the calibration device of Figure

2C mounted on a measurement instrument after a calibration target has been

removed from the device;

Figure 2F is a schematic sectional representation of a calibration device

embodying the invention;

Figure 2G shows the calibration device of Figure 2F mounted on a

measurement instrument after a removable calibration target has been removed from

the device;

Figure 3A is a schematic representation of another calibration device

embodying the invention;

Figure 3B is a schematic representation of the calibration device of Figure 3 A,

positioned adjacent a material or tissue to be measured, with a calibration target

partially removed from the device; Figure 3C shows a measurement system embodying the invention which

utilizes a disposable calibration device as shown in Figures 3A and 3B;

Figure 3D shows the measurement system of Figure 3C with the calibration

device removed;

Figure 3E is a cross-sectional view of a measurement system embodying the

invention that includes a spring loaded annulus at a distal end of the measurement

instrument;

Figure 3F is a flow chart summarizing the steps involved in calibrating a

measurement instrument and taking a measurement on a material or tissue using a

method embodying the invention;

Figure 4 is a perspective view of a structure of a calibration device embodying

the invention;

Figure 5A is a side view of a calibration device embodying the invention;

Figure 5B is a sectional view of another calibration device embodying the

invention;

Figure 6 is a schematic representation of another calibration device embodying

the invention.

Figure 7A is a schematic side view of another calibration device embodying

the invention;

Figure 7B is a front view of the calibration device of Figure 7A; Figure 8 is an exploded perspective view of a calibration target embodying the

invention that could be used in a measuring system embodying the invention;

Figure 9 is an exploded perspective view of a combined calibration/reference

target and infection shield embodying the invention that could be used in a

measuring system embodying the invention;

Figure 10 is a plan view of another calibration/reference target embodying the

invention that could be used in a measuring system embodying the invention;

Figure 11 is another plan view of a calibration/reference target embodying the

invention that could be used in a measuring system embodying the invention;

Figure 12 is a plan view of another calibration/reference target embodying the

invention that could be used in a measuring system embodying the invention;

Figure 13 is a sectional side view of a calibration device embodying the

invention;

Figure 14 is an exploded perspective view of a calibration/reference target and

infection shield that could be used in a measuring system embodying the invention;

Figure 15 A is a side sectional view of a calibration device embodying the

invention;

Figure 15B is a perspective view of the calibration device of Figure 15 A;

Figure 16 is a plan view of another calibration/reference target embodying the

invention that could be used in a measuring system embodying the invention; Figure 17 is a side view of another calibration/reference device embodying the

invention that could be used in a measuring system embodying the invention;

Figure 18 is a perspective view of another calibration/reference device

embodying the invention that could be used in a measuring system embodying the

invention;

Figure 19 is a plan view of another calibration/reference target embodying the

invention that could be used in a measuring system embodying the invention;

Figure 20 is a plan view of another calibration/reference target embodying the

invention that could be used in a measuring system embodying the invention;

Figure 21 is yet another embodiment of a calibration/reference target

embodying the invention that could be used in a measuring system embodying the

invention;

Figure 22 is a diagram of an external light source that can be used with a

measuring instrument and transmissive calibration/reference device embodying the

invention;

Figure 23 is a diagram showing a measuring instrument embodying the

invention performing a calibration operation or a measurement operation utilizing

an external light source;

Figure 24A is a diagram of a measuring instrument embodying the invention; Figure 24B is a diagram showing a measuring instrument embodying the

invention conducting a calibration/reference operation with a transmissive

calibration target;

Figures 25A, 25B, and 25C show front, side and back views, respectively, of

a measurement instrument embodying the invention;

Figure 25D shows a measurement instrument embodying the invention in a

charging stand;

Figure 26A is a schematic diagram of certain elements of a measuring

instrument embodying the invention;

Figure 26B shows a cut away perspective view of an optical unit of the

measurement instrument of Figure 26A;

Figure 27 is a diagram showing a fiber optic bundle of a measurement

instrument embodying the invention adjacent a tissue or material being measured;

Figure 28 is a sectional view of the fiber optic bundle of Figure 27 as seen from

section line 28-28;

Figure 29 is a sectional view of the fiber optic bundle of Figure 27 as seen from

section line 29-29;

Figure 30 is a diagram showing transmit and receiving optical fibers of a

measurement instrument embodying the invention and the path of radiation emitted

or received by the optical fibers; Figure 31 is a block diagram of parts of a measurement instrument embodying

the invention;

Figure 32 is a flow chart showing the steps of a method embodying the

invention for calculating a bilirubin concentration of a patient;

Figure 33 is a diagram showing the results of data taken using the method of

Figure 24 versus a standard serum bilirubin (heel stick) method;

Figure 34 is a flow chart of another method embodying the invention for

calculating a bilirubin concentration of a patient;

Figure 35 is a diagram showing the amplitude of light reflected from a patient's

skin under two conditions, the first condition corresponding to blood in the patient's

skin being 100% oxygenated and the second condition corresponding to the blood

in the patient's skin having no oxygen;

Figure 36 is a diagram showing the amplitude of radiation reflected or

scattered from a patient's skin for explaining how a corrected bilirubin concentration

is calculated using a method embodying the invention;

Figure 37 is a flowchart of a method of performing bilirubin measurements on

a patient embodying the invention;

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The terms "calibration target" and "reference target" are used interchangeably

in the following text to refer to a target having known optical properties. The invention is applicable to both calibration targets and reference targets, and use of

either term should not be construed as limiting. Also measuring instruments

embodying the invention make use of electromagnetic radiation. The terms

electromagnetic radiation, radiation and light are intended to be equivalent terms, all

of which refer to electromagnetic radiation.

Figure 1A is a schematic view of a spectroscopic measurement system 3 in a

calibration mode. The system 3 includes an instrument 10 which outputs

electromagnetic radiation 39 and receives and analyzes radiation reflected back

towards the device by a material or tissue 30 being measured, or that is generated by

the material or tissue 30 in response to the radiation output by the instrument 10.

Alternatively, the instrument 10 may output, receive and analyze acoustic waves.

Reference number 39 will be used to represent electromagnetic radiation or acoustic

waves, just as reference number 10 will be used to represent an instrument that

outputs either electromagnetic radiation or acoustic waves.

The electromagnetic radiation 39 output by the instrument 10, or that is

generated by a material or tissue or a calibration target, may lie within the visible,

infrared, ultra-violet regimes, and/or within the rf, microwave and millimeter wave

regimes. With regard to electromagnetic radiation 39, the instrument 10 can be a

spectrometer, laser radar, radar or any other radiation measuring instrument that

outputs radiation to a material or tissue 40, then measures some portion of a return

signal. With regard to acoustic waves, the instrument 10 can be an acoustic

measuring/imaging device that outputs acoustic waves and measures the return

acoustic wave signal. The discussion that follows is drawn to a device that uses

electromagnetic radiation, it being understood that an analogous discussion applies

for an instrument that uses acoustic waves.

During a calibration procedure, as shown in Figure 1A, radiation 39 is

transmitted toward and through a shield 20 toward a calibration target 30. The shield

20 serves as a barrier between the instrument 10 and a material or tissue 40 to be

measured, and hence functions to reduce contamination of the material or tissue 40.

One major (but not the only) purpose of the shield 20 is to guard against possible

infection when living tissue 40 is measured. Hence, the shield 20 might also be

referred to as an infection shield. A shield 20 must be at least partially transmissive

to radiation 39 such that a portion of the emitted radiation passes through the

window 20 to appear as radiation 39'.

Radiation 39' passes through a region 35 and reaches a surface 41 of the

calibration target 30. The surface 41 can be the same material as the calibration target

30, or a specially applied layer. The surface 41 reflects or scatters radiation back

towards the instrument 10, or emits flourescent or luminescent radiation. Note that

throughout this specification, reflection and scattering are used interchangeably and

are meant to indicate that radiation travels back toward instrument 10. Also, the

region 35 can include a variety of adhesives, gels, pastes, or other materials. Once the system 3 with the instrument 10 is calibrated, the calibration target

30 is removed, and the system 3 is ready to take measurements on a target material

40 through the shield 20. Figure IB shows the system 3 in a measurement mode,

wherein the calibration target 30 has been removed and radiation 39' is now reaching

a tissue or material 40 to be measured through the shield 20.

Figure 2A shows a schematic representation of a calibration device 45

embodying the invention. The calibration device 45 includes a shield supporting

structure 250 with a window 260. Together, the structure 250 and the window 260

comprise the shield 20 shown in Figure 1 A. In alternative embodiments, the window

260 can be an opening in the structure 250, or a transmissive barrier. Any reference

to a window should be read to encompass either an opening or a transmissive

structure, where appropriate. Also, in this embodiment, the supporting structure 250

is shaped like a truncated cone. As a result, the window 260 is circular. It should be

understood, however, that the shape of the shield structure 250 need not be limited

to a cone-type shape, and the window 260 need not be limited to a circular shape.

The calibration device 45 also includes a calibration target 270 (corresponding to the

calibration target 30 in Figure 1A) with a user graspable tab 280. The calibration

target 270 is arranged in the window 260 of the structure 250.

The calibration device 45 receives radiation 39 from an instrument 10. The

radiation 39 passes through the window 260 and the region 35 and reaches the surface

41 of the calibration target 270. The window 260 must be at least partially (and preferably nearly completely) transparent to the radiation 39. The region 35 can

include an adhesive, gel, or liquid which may act as an index matching agent, and/or

free space. In one embodiment, the window 260 is statically charged with respect to

surface 41 of calibration target 270. The static charge holds the calibration target 270

in place. Radiation 39 is then incident on the surface 41 of the calibration target 270.

If the calibration target 270 is to be reflective, it should be configured to have

a known reflection spectrum for calibration purposes (note that the radiation 39 is

scattered or reflected from the calibration target 270 back towards the instrument 10).

For instruments 10 which perform measurements of intensity, independent of

wavelength, a highly reflective surface 41 of the calibration target 270 may be

advantageous. This might include radar, laser radar and interferometric type

instruments. Note, however, that such instruments might also benefit from using a

less reflective surface 41 on the calibration target 270.

Once a measurement system is calibrated, the calibration target 270 is removed

from the window 260 by pulling on a user graspable tab 280, as shown in Figure 2B.

The system 3 is now ready to take measurements on a material or tissue 40 through

the window 260 of the calibration device.

Figures 2C through 2E show an embodiment of the calibration device that

includes an index matching agent. As shown in these figures, the calibration device

includes a structure 250, a calibration target 270 having a calibration surface 41 and

an index matching agent 293 contained within the structure 250 and covered with a seal 290. The index matching agent 293 could be a liquid or a gel that aids the

instrument in taking an accurate measurement.

To use a calibration device that includes an index matching agent, one would

first remove the seal 290 using a user graspable tab 295. The calibration device,

without the seal 290, is shown in Figure 2D. The calibration device would then be

attached to a housing 298 of a measurement instrument, as shown in Figure 2E. The

housing may include a window 294 designed to abut the index matching agent 293

when the structure of the calibration device is mounted on the instrument. A bundle

of optical fibers 299, that transmit and receive radiation, may abut the other side of

the window 294.

Once the structure 250 of the calibration device is mounted on the housing

298 of the measurement instrument, a calibration measurement would be performed

while the calibration target 270 is still attached to the structure 250. After the

measurement instrument has been calibrated, the calibration target 270 would be

removed from the structure 250 so that measurements can be performed on a

material or tissue. All or a portion of the structure 250 may be made of a flexible

material so that the structure 250 can flex when the instrument is pressed against a

target material, or the skin of a patient. This would cause the index matching agent

293 to completely fill the void between the target material/patient's skin and the

window 294 of the measurement instrument. Another calibration device embodying the invention is shown in Figures 2F

and 2G. In this embodiment, the calibration device includes a structure 250 and a

window 297. A calibration target 270 is attached to the structure 250 and an index

matching agent 293 is trapped between the window 297 and the calibration target

270.

The calibration target would be mounted on a housing 298 of a measuring

instrument, as shown in Figure 2G. A bundle of optical fibers 299 can then abut a

first side of the window 297 opposite the index matching agent 293. Once the

calibration device is attached to the measurement instrument, a calibration

measurement can be performed while the calibration target 270 is still attached to the

structure 250. After calibration has occurred, the calibration target 270 could be

removed so that measurements can be performed on a material or tissue.

Figures 3A and 3B correspond to Figures 2A and 2B, but with radiation 39

entering from the right side, and the calibration target 270 attached to the window

260 within the structure 250. In this case, an outer annular ring 306 comes into

contact with a tissue or material 40 to be measured. Structure 250 also includes an

annular ring or ridge 312, which is intended to be used to secure the device 45 to an

instrument 10 (not shown).

Figure 3C shows a measurement system 3 which utilizes a disposable

calibration device 45. Here, the measurement instrument 10 is an optical instrument,

such as a spectrometer, and radiation 39 is electromagnetic radiation which can be in the visible, UV and/or infrared regions. The system 3 includes a housing 343 which

is easily graspable by a human hand. The instrument 10 is coupled to calibration

device 45 via optical fibers 333. The calibration device 45 is inserted into an opening

end 346 of a cone-shaped holder 358 of the housing 343. The cone shaped holder 358

can have any shape depending, among other things, on the shape of the calibration

device. Hence, the holder 358 will alternatively be referred to as a calibration device

receiving element. The holder 358 can be a separate piece, or part of the housing 343.

It is preferable that the holder 358 be capable of receiving the calibration device 45

and allowing the calibration target to be readily removed from the calibration device

so that a measurement may be performed on a material or tissue 40. The holder 358

should also allow the calibration device 45 to be easily removed so that the system

3 is again ready to receive a new calibration device 45.

A curved portion 366 ofthe housing 343 allows the user's hand to comfortably

hold the system 3. A user can initiate a calibration or measurement, as the case may

be, by pressing a push button 361 with his or her thumb. Once a calibration

measurement has been performed, a user graspable tab 280 is used to remove the

calibration target from the window 260 (not shown in this view), and the system 3

is ready to make a measurement on a material or tissue 40.

Figure 3D shows the same measurement system with the calibration device 45

removed. A new calibration device 45 must be inserted into the holding end 346 of

the system 3, the above discussed process of calibration repeated, and the calibration target 270 removed, before the measurement system 3 is ready to perform a new

measurement. Alternatively, a cap 375 can be placed over the holding end 346

between measurements. In all of the above embodiments, the calibration target 270

can have calibration information fitted directly on the surface 41 of the calibration

target 270. This calibration information can include a message read by the

instrument 10, or a particular pattern that can be recognized by the instrument. In

such a system, if a calibration target does not include the predetermined message or

pattern, the instrument could be configured to shut down. This would prevent the

use of unauthorized calibration targets, which would help to ensure the instrument

is always properly calibrated.

Figure 3E shows a cross-sectional view of a measurement instrument

embodying the invention. The instrument includes a measurement device 10 coupled

to an output end 370 of the system 3. An annulus 372, that surrounds a bundle of

optical fibers 333, is mounted on the output end 370 of the system 3. The annulus

372 is mounted on the system 3 utilizing a spring 373, which biases the annulus 372

outward away from the measurement system 3. The annulus 372 may also be

connected to a device that senses the position of the annulus 372 relative to the

housing of the system 3.

According to one embodiment of the invention, the measurement device

functions independently of spring 373 in that a measurement can be made regardless

of whether or not spring 373 is biased. According to another embodiment of the invention, when a user performs a measurement using the measurement system 3, the

user would push the instrument against a surface of a target material, or the skin of

a patient, so that the annulus 372 moves inward, against the bias of the spring 373.

The movement would be sensed by a proximity sensing device. The proximity

sensing device could then be used to output a signal when the annulus 372 is pushed

far enough into the measurement system 3 such that a measurement can be

performed by the measurement system 3. In a measurement system including a

spring biased annulus 373, the proximity sensing device could be used to disable the

device when the annulus 373 is too far out, and to enable the device to take a

measurement when the annulus 372 is pushed a sufficient distance into the device

such that a measurement can be accurately performed. The proximity sensing device

could be a simple switch having electrical contacts, or a light emitter and

corresponding sensor. Alternatively, the proximity sensor could directly sense the

proximity of an output end of the measurement instrument to a target material or

tissue using an optical system or some other equivalent sensor, as would be well

known in the art.

Figure 3F summarizes the steps involved for the system 3 to take a

measurement on a material or tissue 40. In particular, step 382 involves placing a

calibration device 45 on the end 346 of the system 3. At this point, the calibration

45 device still has a calibration target 270 covering the window 260. A calibration

measurement is performed by the system 3 at step 384 by pressing a push button 361, which activates the measurement instrument 10. Step 388 involves removing the

calibration target 270 from the window 260. Step 392 then involves performing a

measurement on a tissue or material 40 to be measured. This might involve a single

measurement or multiple measurements (if cross contamination is not an issue) on

the same or a similar tissue or material. That is, multiple measurements might be

taken in one vicinity, or at different locations on a material or tissue. The results of

the multiple measurements could be averaged or interpreted to arrive at a

measurement result. Finally, once the measurement or measurements have been

completed, the calibration device 45 is removed, discarded, and replaced with a new

calibration device 45 at step 396. Alternatively, a used calibration device 45 can be

removed, discarded, and a cap 375 can be placed over the end 346 until a new

measurement is to be made.

A calibration/reference device embodying the invention, that could be used

with a measuring system embodying the invention, may be comprised of several

parts. The first part is simply a device for anchoring a contamination/infection

shield and a calibration/reference target to a measuring instrument. If the instrument

is like the one shown in Figure 3C or 3E, a shield holder 110, as shown in Figure 4,

can be used to attach an infection/contamination shield and a calibration/reference

target to the nose portion of the measuring instrument.

As seen in Figures 4, 5 A and 5B, the shield holder 110 has a plurality of finger¬

like projections 114 arranged in a cylindrical shape. Some or all of the projections 114 may include a lip 116 which is engageable with the nose portion of the

instrument to attach the device to the instrument. The projections might also engage

a spring loaded mechanism like the one shown in Figure 3E. If the shield holder 110

is made from a flexible material, such as a molded plastic, the shield holder 110 can

be snapped onto the nose of the instrument so that the lips 116 engage the nose.

A multilayer combined contamination shield and calibration target 200 can

then be affixed to a front annular surface 112 of the shield holder 110, as shown in

Figure 5A. In a preferred embodiment of the invention, the combined

contamination shield and calibration target 200 is attached to the shield holder 110

with a layer of adhesive. The combined contamination shield and calibration target

200 may include a user graspable tab 202 for removing the calibration target after a

calibration or reference operation has been performed.

Of course a calibration target 200 could also be mechanically attached to the

shield holder 110 by any type of mechanical attachment mechanism such as staples,

clips, pins, etc. Figure 17, which is described in more detail below, shows an

embodiment where a calibration target 206 is attached to a shield holder 110 with a

plurality of pins 220 arranged around the periphery of the shield holder 110.

In an alternate embodiment, as shown in Figure 5B, an infection shield 204

may be separately mounted to the shield holder 110. The infection shield 204 could

simply be a clear plastic portion of the shield holder 110, which is integrally molded

with the shield holder 110. The infection shield 204 could also be a substantially transparent film that is attached to the shield holder 110. A calibration target 206

could then be attached to the front annular surface 112 of the shield holder 110 via

an adhesive layer or some type of mechanical attachment device. The calibration

target 206 would include a user graspable tab 202 for aiding removal of the calibration

target after a calibration or reference operation has been performed.

Figure 6 shows a calibration device 45 according to another embodiment of

the invention. Here, a landing annulus 690 is affixed to the structure 250. The

landing annulus 690 serves to fix the angle at which radiation is incident on the

surface 680 of a material or tissue 40 being measured. The landing annulus 690 is

preferably transparent to radiation 39. Calibration occurs, as before, using the

calibration target 270. The calibration target 270 is then removed, and the annulus

690 remains in place. The measuring instrument, is then placed on the surface 680,

such that the annulus 690 lies flat on the surface 680. This ensures that radiation 39

is incident approximately normal to the surface 680, as it was to the surface 41 of the

calibration target 270. On the other hand, depending on the type of measurement,

it may be preferable, due to unwanted spectral reflections, to have radiation 39

incident at an angle relative to an axis normal to the surface 680. The landing

annulus 690 can be a separate piece affixed to the structure 250 and comprised of any

type of rigid material such as various plastics. If infection to the surface 680 of tissue

40 is an issue, then the landing annulus 690 should be removable from the structure

250. Alternatively, annulus 690 can simply be an extension of window 260 itself. The structure 250 is preferably fabricated from molded plastic with a smooth

window zone defined for the window 260. Using plastic molding allows the

structure 250 to be fabricated at low cost and in a wide variety of shapes and sizes.

The calibration target 270 can also be fabricated from plastic and may also have a dye

or other material added to the surface 41 to provide sufficient spectral detail to effect

the necessary calibration. The calibration target 270 can be attached to the window

section 260 in such a way that once removed, it cannot be readily re-attached. One

implementation is to fabricate the calibration target 270 using a statically clinging

type plastic, and to fabricate structure 250 using an appropriate material such as an

acrylic called polymethyl methacrylate (PMMA), both of which are available from

3M Corporation.

Figure 7A shows a side view of a calibration device 45 according to yet another

embodiment of the invention. Here, the calibration target 270 is held in place by a

ridge 700 alone, or together with static cling between the calibration target 270 and

the window 260. The ridge 700 can be part of the window 260, or a separate piece.

Figure 7B shows the calibration device 45 as viewed from above.

A calibration/reference target that could be used with a calibration target

embodying the invention is shown in Figure 8. The target includes a calibration

layer 470 having a central portion 474 with known optical properties. A user

graspable tab 472 is formed as a part of the calibration layer 470. Also, a double-sided

adhesive layer 440 is used to attach the calibration layer 470 to a shield holder 110, as shown in Figure 5B. In alternate embodiments, the adhesive layer 440 can be used

to attach the calibration layer 470 to an infection/contamination shield layer which

is then attached to the shield holder 110, as shown in Figure 5 A. Also, the adhesive

layer 440 could be used to attach the calibration layer 470 directly to a measuring

instrument. In still other embodiments, the double-sided adhesive layer 440 could

be replaced with an adhesive that is applied to the calibration layer 470 in a liquid,

gel or paste form.

In preferred embodiments, the calibration layer 470 and the double-sided

adhesive layer 440 are carefully constructed so that when the calibration target is

removed from a shield holder, the target portion 474 in the center of the calibration

layer 470 will tear in a predetermined manner. To that end, the calibration layer 470

may include a reduced strength portion 480, which could be a slit, a perforation or

a crease. The reduced strength portion 480 in the embodiment shown in Figure 8 is

a perforation that extends from a peripheral edge of the calibration layer 470, towards

the central area 474. When a user grasps the tab 472 and pulls on the tab to remove

the calibration layer 470 from a shield holder, the calibration layer 470 will tend to

tear along the reduced strength portion 480.

In the embodiment shown in Figure 8, the adhesive layer 440 has a horseshoe

shape such that a portion of the calibration layer 470 having the reduced strength

portion 480 is aligned with the gap in the adhesive layer 440. Also, in a preferred

embodiment, a first side 442 of the adhesive layer 440 will have a relatively low adhesive strength, and the opposite side of the adhesive layer 440 will have a greater

adhesive strength. In this configuration, the lower adhesive strength side 442 of the

adhesive layer 440 is used to attach the calibration layer 470 to a shield holder. When

a user pulls on the tab 472 to remove the calibration layer 470, the lower adhesive

strength side 442 will separate from the shield holder before the higher adhesive

strength side separates from the calibration layer 470. Thus, the adhesive layer 440

is fully removed along with the calibration layer 470. Also, because of the gap in the

adhesive layer 440, the portion of the calibration layer immediately to the right of

the reduced strength portion 480 will tend to remain attached to the shield holder

while the portion of the calibration layer 470 adjacent the tab and located beneath the

gap in the adhesive layer 440 will pull upward and away from the shield holder. This

will cause the calibration layer 470 to begin to tear along the reduced strength

portion 480. As the user continues to pull on the tab 472, the tearing of the

calibration layer 470 will tend to continue across the center portion 474 having the

optical properties used to perform a calibration operation.

If a liquid, gel or paste adhesive is used to attach the calibration layer 470 to

a shield holder 110, there will not be varying adhesive strengths. However, in such

an embodiment it would be advantageous if the adhesive had a greater affinity for the

calibration layer 470 than for the shield holder 110. In this case, most, if not all, of

the adhesive would remain attached to the calibration layer 470 as it is removed from

the shield holder 110. Thus, no adhesive remaining on the shield holder 110 would contact the skin of a patient or a surface to be measured when the instrument and

attached shield holder 110 are used to take a measurement.

Similarly, if some type of mechanical attachment mechanism is used to attach

the calibration layer 470 to a shield holder 110, it may be advantageous if the

mechanical attachment mechanism is more firmly attached to the calibration layer

470 than to the shield holder 110. This would result in the attachment mechanism

being removed from the shield holder along with the calibration layer, leaving the

shield holder 110 free of any protrusions when used to take a measurement. For

instance, in the embodiment shown in Figure 17, the pins 220 attaching the

calibration target 206 to the shield holder 110 could be more firmly attached to the

calibration target than the shield holder 110. The cylindrical shafts of the pins 220

would extend through the annular portion 112 of the shield holder 110. Ends of the

pins 220 that protrude out the back side of the annular portion 112 could have a

slightly enlarged diameter, thus holding the pins 220 and the attached calibration

target 206 firmly to the shield holder 110. When the user pulls the calibration target

206 away from the shield holder 110, the pins 220 will pull out of the holes in the

annular portion 112. Also, by arranging the pins in a particular orientation with

respect to the user graspable tab 202 of the calibration target 206, the calibration

target can be caused to tear or separate in a predetermined manner.

Once a calibration layer 470 has been completely removed from a shield

holder, the central portion 474 of the calibration layer 470 should be irrevocably damaged so that the calibration layer 470 cannot be re-used for a new calibration

operation. In the embodiment shown in Figure 5B, because the side of the adhesive

layer 440 in contact with the calibration layer 470 has a greater adhesive strength than

the side 442 which was attached to the shield holder, all of the adhesive layer should

remain attached to the calibration target and be removed from the shield holder

along with the calibration layer 470.

As mentioned above, the calibration target shown in Figure 8 is intended to

be used with a shield holder 110 as shown in Figure 5B. This type of shield holder

110 includes its own integral infection/contamination shield 204.

In an alternate embodiment, as shown in Figure 9, both a calibration target

and an infection/contamination shield are attached to the exterior of a shield holder.

In this embodiment, a first double-sided adhesive layer 410 is attached to a front edge

112 of a shield holder 110, like the one shown in Figure 5A. The opposite side of the

adhesive layer 410 is then attached to a infection/contamination shield 420. In a

preferred embodiment, the infection/contamination shield 420 is substantially

transparent. An adhesive layer 440 and a calibration layer 470 are then attached to

the infection shield 420. The adhesive layer 440 and the calibration layer 470 have

generally the same properties as those described for the embodiment shown in Figure

8. That is, a first side 442 of the adhesive layer 440 has a relatively low adhesive

strength, and the opposite side of the adhesive layer, which is attached to the

calibration layer 470, has a greater adhesive strength. Thus, when a user pulls the tab 472 of the calibration layer 470 and removes the calibration layer, both the

calibration layer and the adhesive layer 440 are removed. This leaves just the

infection/contamination shield 420 attached to the shield holder 110 and the

instrument 100. Of course the double-sided adhesive layers 410 and 440 could also

be replaced with a liquid, gel or paste adhesive, or with a mechanical attachment

device, as described above.

Once a calibration/reference operation has been conducted, and the

calibration target is removed, the instrument can be used to conduct a measurement

on a patient or an object. In one embodiment, light generated by the instrument

passes through the infection shield 420, strikes the patient or object, and is reflected

back through the infection shield 420 to a detector of the device. In an alternate

embodiment, light generated by the instrument would pass through the infection

shield 420, strike the patient or object, and the target patient or object would emit

fluorescent or phosphorescent emissions in response to the emitted light. The

fluorescent or phosphorescent emissions would pass back through the infection

shield and would be detected by the instrument. After a patient or object

measurement has been completed, the shield holder 110 and the attached infection

shield 420 are removed from the instrument 100 and disposed of.

The calibration layer 470 can have a reduced strength portion 480 configured

in many different ways. In the embodiments shown in Figures 8 and 9, the reduced

strength portion extends from a peripheral edge towards a center 474 of the calibration layer 470. This encourages the calibration layer to tear across the center

portion 474, which is the portion having optical properties used to calibrate a

measuring instrument. In preferred embodiments, the reduced strength portion 480

does not extend beyond the annular radial width of the adhesive layer 480 so that

light cannot penetrate through the calibration layer 470 and affect a calibration or

reference operation.

In the embodiment shown in Figure 10, a calibration target 270 can be

manufactured with two user graspable tabs at its sides. Here, two pull tabs 531 and

533 are attached to two halves 535 and 537 of the calibration target 270. Between the

two halves 535 and 537 is a mechanical perforation 539. When the calibration target

270 is pulled away from a structure of the calibration device by one of the tabs, it

breaks along perforation 539, thereby making it difficult or impossible to reuse. The

remaining half of the calibration target 270 can then be pulled away using the

remaining tab.

In other alternate embodiments, as shown in Figures 11 and 12, the reduced

strength portion can have different configurations. In the embodiment shown in

Figure 11, the reduced strength portion 480 traverses a path across the central region

474 of the calibration layer 470. In the embodiment shown in Figure 12, the reduced

strength portion 480 proceeds in a direct line across the center 474 of the calibration

layer 470. Each of these embodiments is intended to ensure that as the calibration layer 470 is removed, the central portion 474 used to calibrate the instrument is

altered in a destructive manner so that the calibration layer cannot be reused.

In still other embodiments, a cutting device could be incorporated into the

calibration layer 470, or into the shield holder 110 or the instrument itself. One such

embodiment is shown in Figure 16, where a wire or monofilament 478 is attached to

or embedded in the calibration layer 470. The wire or monofilament 478 will cause

the calibration layer 470 to tear in a predetermined manner when a user pulls on the

tab 472. Although Figure 11 shows the wire or monofilament extending only

partway across the calibration layer 470, the wire or monofilament could extend

further or completely across the calibration layer 470. The wire or monofilament

could also be arranged in a pattern, like the reduced strength portion 474 shown in

Figure 11.

In alternate embodiments, a wire or monofilament could also be attached to

the shield holder. In the embodiment shown in Figure 18, a wire or monofilament

230 is stretched across the back of the calibration layer 200, with ends of the wire or

monofilament being attached to the shield holder 110. Also, the wire or

monofilament 230 could be replaced with any other type of cutting device that will

cause the calibration layer 470 to tear or separate in a predetermined manner when

being removed from a measuring instrument.

If the measuring instrument 100 embodying the invention is configured so that

only a single patient or object measurement may be conducted after each calibration operation, use of the calibration device can help to prevent patient infection or

patient or object cross-contamination.

When a user attempts to use the measuring instrument, a shield holder with

an infection/contamination shield and a calibration target will first be attached to the

instrument. Next, a calibration/reference operation will be performed. Once the

calibration/reference operation is complete, the user will grasp a tab on the

calibration target and pull on the tab to remove the calibration target. This will cause

the calibration target and any attached adhesive layer to be removed from the shield

holder. The act of removing the calibration target will destroy at least the portion

of the calibration target having the optical properties used to calibrate/reference the

instrument. Thus, it will be impossible to reuse the calibration target. The user

would then proceed to conduct a patient or object measurement with the shield

holder and infection shield still attached to the instrument. The results of the

measurement can then be noted or recorded.

Because the instrument will not perform a second patient or object

measurement without first performing another calibration/reference operation, the

user will be forced to remove both the shield holder and the infection shield and

replace it with a new device that includes a new calibration target. The user will be

forced to perform another calibration operation before the device can be used to

perform another patient or object measurement. For this reason, it should be

impossible for the device to be used to take two measurements on two different patients or objects using the same shield holder and infection/contamination shield.

This prevents cross-contamination between different patients or objects.

Also, an interlock mechanism in the measuring instrument may interact with

a shield holder to inform the instrument when a shield holder is removed. The

instrument can then be configured so that no patient or object measurements can be

performed once a shield holder has been removed from the instrument. This should

discourage users from attempting to conduct a measurement without an

infection/contamination shield in place, thereby reducing the opportunity for patient

or object cross-contamination. Similarly, the interlock mechanism could be

configured to prevent more than one patient or object measurement cycle from being

performed before a shield holder is removed and another one is inserted.

In a preferred embodiment of the invention, the shield holder is configured as

shown in Figure 5A, and a combined infection/contamination shield and calibration

target 200 will be constructed as shown in Figure 14. In this embodiment, a first

double-sided adhesive layer 410 is used to attach the combined

infection/contamination shield and calibration target to the shield holder 110. The

opposite side of the double-sided adhesive layer 410 is adhered to a shield layer 420.

Next, a clear release liner 430 is attached to the infection/contamination shield 420.

The release liner 430 will remain permanently attached to the infection shield 420,

but will provide a controlled release of the remaining portions of the combined

infection shield and calibration target. Next, a second double-sided adhesive layer 440 is attached to the release liner

430. As in the previous embodiments, a gap is formed in the adhesive layer 440.

Next, a spacer layer 450 is attached to the opposite side of the second adhesive layer

440. The spacer layer 450 serves to space a calibration layer a precise distance from

an emitting end of an instrument to which the device is attached. A third double-

sided adhesive layer 460 then attaches a calibration layer 470 to the spacer layer 450.

The double sided adhesive layers 410, 440 and 460 could all be replaced with

a liquid, gel or paste adhesive, or by a mechanical attachment device, as explained

above.

The central portion 474 of the calibration layer 470 will be exposed to light

emitted by an emission end of an instrument to which the device is attached. Also,

reduced strength portions are formed in the spacer layer 450, the third double-sided

adhesive layer 460 and the calibration layer 470. As explained above, the reduced

strength portions cause the calibration layer 470 to tear in a predetermined manner

when the calibration layer 470 is removed from the remaining portions of the device.

Also, the reduced strength portions are oriented in a predetermined manner with

respect to the gap in the second double-sided adhesive layer 440. Preferably, the

reduced strength portions are positioned adjacent one side of the gap. When the

device is oriented in this manner, pulling on the tab 472 of the calibration layer 470

causes the calibration layer to tear along the reduced strength portion 480 and to

irrevocably damage the central portion 474 of the calibration layer 470. Of course, the reduced strength portions could also be replaced by a cutting

device, as explained above, to cause the calibration layer to tear or separate in a

predetermined manner.

In alternate embodiments, the shield holder could be configured as shown in

Figure 13. In this embodiment, the narrower portion of the shield holder is to be

attached to a measuring instrument, and the larger diameter flared portion 112

extends away from the device. A flexible annular ring of material 210 on the rear of

the shield holder may engage projections on the nose portion of a measuring

instrument. In this embodiment, a combined infection/contamination shield and

calibration target 200 is located adjacent the back side 208 of the shield holder 110,

instead of being located on the front end 112. The combined

infection/contamination shield and calibration target 200 still includes a user

graspable tab 202 which can be pulled to remove the calibration target. This

embodiment, like the embodiment shown in Figure 5B, could have an infection

shield mounted on the shield holder and a separate calibration target which is adhered

to the shield holder or the infection/contamination shield.

Another alternate embodiment of a calibration/reference device is shown in

Figures 15A and 15B. In this embodiment, a calibration target holder 125 has a cup¬

like shape. A calibration target 126 may be mounted on the inside of the holder 125,

as shown in Figure 15A. Alternatively, if the holder 125 is transparent, the

calibration target 126 could be mounted on the outside of the holder 125. The holder 125 could be formed of any rigid or semi-rigid material. In a preferred embodiment,

the holder 125 would be made of molded plastic. The calibration target 126 could be

pre-mounted on the holder 125, such that the entire assembly can be used for a

period of time, then discarded. Alternatively, the calibration target 126 could be

removably mounted on the holder 125, such that the holder 125 can be re-used

multiple times with different calibration targets 126. In this instance, the calibration

target 126 could include a user graspable tab 127 that aids removal of the calibration

target 126 from the holder 125.

To use this type of calibration device, the user would place the calibration

device over the detector of a measuring instrument. For instance, the calibration

device could be placed over the nose of a measuring instrument. The measuring

instrument would then conduct a calibration operation using a portion of the

calibration target 126 having known optical properties. The user would then remove

the calibration device from the measuring instrument and conduct a measurement on

a target object or tissue.

An embodiment like the one shown in Figures 15A and 15B could be used

with a measuring device that does not require a calibration operation to be performed

prior to each measurement. This embodiment could be used for periodic calibration

of a measuring device. The holder would ensure that the calibration target is

correctly positioned relative to the light source and detector of the measuring

instrument. Also, the sidewalls of the holder 125 would serve to block outside light from reaching a detector of the device, thereby ensuring the calibration operation is

accurate.

In a preferred embodiment of the device, the calibration target 126 would be

removably mounted on the holder 125. The user would obtain a calibration target

126 and first place the calibration target 126 on the inside of the holder 125. The user

would then conduct a calibration operation as described above. After the calibration

operation has been performed, the user could remove the calibration target 126 from

the holder 125 using the user graspable tab 127, so that the holder can be re-used with

another calibration target 126.

Either of the calibration targets shown in Figures 8 and 9 could be used with

the holder 125 shown in Figures 15A and 15B. If the calibration target shown in

Figure 8 is used, the double sided adhesive layer 440 could be used to attach the

calibration layer 470 to the inside of the holder 125. In this instance, the calibration

layer 470 would have known optical properties on the side of the calibration layer

470 opposite the adhesive layer 440, which is the side that would face the detector of

a measuring instrument.

If the calibration target shown in Figure 9 is used, an additional adhesive layer

on the side of the calibration layer 470 opposite the adhesive layer 440 could be used

to attach the calibration device to the holder 125. In this instance, when the holder

is placed over the output end of the measuring instrument, the double sided adhesive

layer 410 would be pressed against and adhere to the measuring instrument. Then, after a calibration operation has been performed, when the holder 125 is removed

from the measuring instrument, it will leave the entire calibration target attached to

the measuring instrument. The user would then remove the calibration layer 470,

and its attached adhesive layer 440, so that the shield layer 420 and the double sided

adhesive layer 410 remain attached to the measuring instrument. The instrument

could then be used to conduct measurements, and the shield layer 420 would act as

a contamination or infection shield. Also, in alternative embodiments, the adhesive

strength of the adhesive layers could be designed such that removal of the cover 125

from the measuring instrument, after a calibration operation, will cause the

calibration layer 470 and adhesive layer 440 to also be removed from the measuring

instrument. This would leave the measuring instrument, with the shield layer 420

and adhesive layer 410, ready to perform a measurement operation. The user could

then remove the calibration layer 470 from the holder 125 so that the holder 125 can

be re-used. Alternatively, the holder 125 and the attached calibration layer 470 and

adhesive layer 440 could simply be discarded.

Also, the portion of a calibration/reference target having known optical

properties need not be simply reflective. In an alternate embodiment, a target layer

of a calibration device embodying the invention could include a fluorescent portion

which emits fluorescent electromagnetic radiation in response to an excitation light.

An embodiment of a fluorescent calibration layer is shown in Figure 19. In this

embodiment, a fluorescent portion 473 is centered on the calibration layer 470. When a calibration device that includes a fluorescent calibration layer is

attached to a measuring instrument, light from a light source of the measuring

instrument can be used to excite the fluorescent portion 473. The fluorescent

portion 473 would then emit fluorescent electromagnetic radiation, which can be

detected by a detector of the measuring instrument. The fluorescent light emitted by

the fluorescent portion 473 may be at a different wavelength than the light used to

excite the emissions. Thus, a fluorescent calibration device can be used to calibrate

an instrument for light emissions in a different portion of the spectrum than would

be possible with a reflective calibration device.

Also, a calibration/reference operation performed with a fluorescent

calibration/reference target could be designed to determine time characteristics of the

fluorescent target. For instance, the fluorescent target could be illuminated with a

relatively short duration burst of excitation light, then the fluorescent emissions from

the fluorescent target could be monitored to determine the amount of time that

elapses before an amplitude of the fluorescent emissions decay below a threshold

value. The details of such a method are provided in U.S. Patent No. 5,348,018 to

Alfano et al, the contents of which are hereby incorporated by reference.

In an alternate method of conducting a calibration/reference operation with

a fluorescent target, the fluorescent target could be illuminated with an amplitude

modulated beam of excitation light. Because an amplitude of the excitation light

modulates with time, an amplitude of the fluorescent light would also modulate with time. A detector of a measuring instrument could monitor the fluorescent light

generated by the fluorescent target and compare the amplitude modulation of the

fluorescent light with the amplitude modulation of the excitation light. A phase shift

between the excitation light and fluorescent light provides an indication of the time

characteristics of the fluorescent target. Also, a demodulation factor, which

represents a ratio of the amplitudes of the excitation light to the amplitudes of the

fluorescent light could be used, in conjunction with the phase shift, to determine

properties of the fluorescent calibration device. Details of such a method are

provided in U.S. Patent No. 5,628,310 to Rao et al., the contents of which are hereby

incorporated by reference.

In still other methods of using a fluorescent calibration/reference target,

polarization characteristics of fluorescent light generated by the target, with respect

to a polarization of the excitation light, can be used to determine time characteristics

of the fluorescent target. In this method, a polarized excitation light would

illuminate the fluorescent target. The detector mechanism of the measuring

instrument would be configured to determine polarization characteristics of

fluorescent light output by the fluorescent target in response to the excitation light.

The polarization characteristics of the fluorescent light, with respect to the

polarization of the excitation light could also be used to determine time

characteristics of the fluorescent target. Details of such a method are provided in U.S. Patent No. 5,515,864 to Zuckerman, the contents of which are hereby

incorporated by reference.

In yet another embodiment, as shown in Figure 20, a calibration layer 470

includes a central region having a fluorescent portion 473 and a portion 474 having

known scattering/reflection properties. When a calibration device including a

calibration layer as shown in Figure 20 is mounted on a measuring instrument, light

emitted from a light source of the instrument can both scatter/reflect off the portion

474 having known properties, and the light can excite fluorescent emissions from the

fluorescent portion 473. The scattered or reflected light, and fluorescent emissions

from the fluorescent portion 473 can be detected by a detector of the measuring

instrument and used to calibrate or reference the instrument.

In still another embodiment, as shown in Figure 21, a fluorescent portion 473

may be centered within a region 474 having known scattering/reflective properties.

Alternatively, the portion having known scattering/reflective properties could be

centered in a larger fluorescent portion. When a target layer 470, as shown in Figure

21, is incorporated in a calibration device embodying the invention, both light

scattered by the portion 474 and fluorescent light emitted by the fluorescent region

473 can be used in a calibration or reference operation.

The two portion calibration layers 470 shown in Figures 20 and 21 allow for

a calibration operation to rely on light having different wavelengths. The light

reflected from the portion 474 having known optical properties will be at the same wavelength as the light emitted by the measuring instrument. Fluorescent light

generated by the fluorescent portion 473 will be at a different wavelength. This type

of calibration/reference operation could be particularly useful for measuring

instruments that utilize light at more than one wavelength to conduct a measurement

operation. This type of calibration/reference operation could also be useful for a

device that utilizes both fluorescent light generated by a target object, and light that

is scattered or reflected from the target object to conduct a measurement operation.

Also, even when a calibration target having a fluorescent portion is used, by

selectively receiving only the same wavelengths that were emitted by the measuring

instrument, one can conduct a calibration based on scattered light. By selectively

receiving only the wavelengths corresponding to fluorescent light generated by a

target, one can conduct a calibration operation based only on the fluorescent light,

thereby preventing reflectance/scattering properties of the target from affecting the

calibration operation.

Each of the methods of measuring fluorescent radiation described above could

also be used by a measuring system embodying the invention to measure fluorescent

light that is generated by a target object or a target tissue of a patient. For instance,

after a calibration or reference operation has been conducted with a fluorescent

calibration target, the calibration target would be removed, leaving a structure of the

calibration device attached to the measuring instrument. The measuring instrument

could then be used to excite and measure fluorescent radiation from a target object or tissue. In a preferred embodiment, excitation light from the measuring instrument

would be used to excite fluorescent emissions from a target object or tissue. The

fluorescent emissions would pass through the structure of the calibration device that

remains on the instrument, to a detector of the instrument, which measures the

fluorescent emissions. Such a target object or tissue measurement could be conducted

by using the burst and monitor method, the phase shift method, or the polarization

sensing method.

In a method embodying the invention, the measuring instrument first takes

readings against a reference target, then takes readings against the skin of a patient or

the surface of an object. The patient or object readings are then compared with the

reference target readings to provide a meaningful output value. This output value

may be expressed as an optical density (OD). A formula for calculating an optical

density in a method embodying the invention is shown below in Equation (1).

OD = - Log₁₀ (Skin - SkinDark)_; (1)

(Ref - RefDark)_s

In a method embodying the invention, the measuring instrument is used with

the reference target to obtain two values. First, a reading is taken against the

reference target with a light source of the instrument turned off. This is referred to

as a dark reference reading, which is abbreviated as RefDark in Equation (1). Next, a reading is taken on the reference target with a light source of the measuring

instrument turned on. This is referred to as a reference reading, which is abbreviated

Ref in Equation (1). Both of these measurements would typically be conducted at a

particular wavelength.

Next, two readings are taken on a patient's skin or on an object. The first

reading is taken with the light source turned off to provide a dark skin reading. This

is abbreviated SkinDark in Equation (1). Next, a reading is taken against the skin of

the patient or on the object with the light source of the measuring instrument turned

on to obtain a patient/object reading. This is abbreviated Skin in Equation (1). The

dark skin reading is then subtracted from the skin reading to provide a corrected

patient/object reading. The dark reference reading is also subtracted from the

normal reference reading to provide a corrected reference reading. A negative

logarithm is then taken of the ratio of the corrected patient reading to the corrected

reference reading. This provides an optical density value which can be used to

diagnose a condition of the patient.

In alternate methods embodying the invention, a plurality of dark skin

readings and normal skin readings may be conducted at multiple different locations

on a patient's skin. The difference between the normal skin reading and the dark

skin reading at each of the different locations can then be averaged to provide the

value for the numerator of Equation (1). Furthermore, in alternative methods embodying the invention, two or more

patient readings may be conducted at different wavelengths, and the results of each

of the readings may provide a plurality of different optical density values that are

then combined to determine a condition of the patient.

Still further, both the skin and reference readings described above may be

corrected for "stray light." Theoretically, there is no light with a wavelength lower

than 350 nm or with a wavelength higher than 850 nm. Signal levels detected at such

wavelengths are considered "stray light." A method for correcting for stray light is

described below with reference to Equation (2).

(I(λ))_s = (I(λ) - [1(330) - 1(330) - 1(900) (λ-330)] (2)

(900-300)

If I(λ) represents a corrected skin reading or a corrected reference reading, as

described above, these readings can be corrected for stray light using Equation (2)

shown above. The correction for stray light requires that the intensity of light be

measured at 330 nm to provide a value 1(330), and that the intensity of light at 900

nm be measured to provide a value 1(900). These values are then inserted in Equation

(2), shown above, to provide a stray light corrected intensity value (I(λ))_s. These stray

light corrected intensity values for the corrected skin intensity and the corrected

reference intensities are used in Equation (1) above to provide an optical density value

which can be used to diagnose a condition of a patient. Furthermore, a measuring system embodying the invention could be

configured to measure light from a target object or tissue at more than one

wavelength. For instance, in embodiments where light from the measuring

instrument illuminates the target object or tissue and is scattered or reflected back to

the measuring instrument, a detector of the instrument could measure the reflected

or scattered light at multiple wavelengths.

In still other embodiments of the invention, the target layer 470 of a

calibration target could be partially transmissive so that light transmitted through the

target layer can be used to perform a calibration or reference operation. For instance,

in the embodiment shown in Figure 8, the central region could have known

transmissive properties so that light transmitted through the central region 474 may

be used to perform a calibration or reference operation. Two methods for

performing a calibration or reference operation using a transmissive calibration target

will now be described with reference to Figures 22, 23, 24 A ad 24B.

Figure 22 shows an external light source that can be used to perform a

transmissive calibration or reference operation, and to conduct a transmissive

measuring operation. The external light source 240 includes a light source 242, which

can be in the form of an incandescent or fluorescent bulb, a light emitting diode, a

laser, or any other device capable of generating electromagnetic radiation. An

aperture 244 allows light from the light source 242 to escape the device. A slot 246, or any other type of mechanical attachment mechanism, can be used to mount a

sample to be measured in the aperture 244 of the light source 240.

Figure 23 shows a measuring instrument 100 being used to conduct a

calibration or measurement operation using the external light source 240. If a

calibration operation is to be performed, the light source 242 is turned on, and a

calibration or reference device is mounted on the measuring instrument 100. The

calibration device would include a calibration/reference target mounted on a shield

holder 110. The calibration device is then pressed against the aperture 244 of the

external light source 240. Light from the light source 242 passes through the

aperture, and a portion of the light also passes through the calibration device. The

light transmitted through the calibration device is received by a detector within the

measuring instrument 100 and is used to conduct a calibration or reference operation.

In some embodiments of the device, a clear window 248 may be mounted in the

aperture 244, and the calibration target may be pressed directly against the window

248.

Once a calibration or reference operation has been successfully performed, the

calibration layer of the calibration device would be removed so that the device is

ready to conduct a patient or object measurement. Removal of the calibration device

could leave a shield holder 110 and an associated infection shield attached to the

measuring instrument 100. An object to be measured may then be mounted on a

slide 248 that is inserted into the aperture 244 of the external light source 240. The shield holder 110, without the calibration target, would then be pressed against the

slide 248, and the measurement device would be activated to conduct a measurement.

Light from the light source 242 would pass through the slide 248, the sample

mounted thereon, and the infection shield and shield holder 110, and the transmitted

hght would be detected by a detector of the measuring instrument 100. The

transmitted light would then be used to conduct a measurement operation.

This type of an embodiment could be useful for measuring optical properties

or colors of objects capable of being mounted on slides 248 that are inserted into an

external light source 240. In alternate embodiments, the measurement operation

could be performed directly on an object without the use of the external light source

240. In this embodiment, the external light source 240 would be used only to

perform a calibration or reference operation with a transmissive calibration target.

In the embodiment shown in Figures 24A and 24B, a light source of the

measuring instrument would be used to conduct a transmissive calibration and/or

measuring operation. The measuring instrument 100 would include a means for

applying light to a calibration/reference target mounted on the instrument 100. The

means could include a light source inside the instrument 100 which transmits light

through an optical fiber to a light head 251. In alternate embodiments, the light head

251 could include an integral light source. In either event, the light head 251 may be

attached to a retractable tether 252 for holding the light head 251 in place on top of

the instrument 100 when it is not in use. If an optical fiber is used to conduct light from a source inside the instrument to the light head 251, the optical fiber could be

inside the tether 252.

With an embodiment like the one shown in Figures 24 A and 24B, a shield

holder 110 and an attached transmissive calibration target would be mounted on a

nose portion 104 of the measuring instrument 100. Next, the retractable light head

251 would be pulled out of the device and placed over the transmissive calibration

target attached to the shield holder 110. The device would then be activated so that

light is emitted from the light head 251, is transmitted through the transmissive

target, and is detected by a detector of the instrument 100 so that a

calibration/reference operation may be performed.

Once a calibration/reference operation has been performed, the light head 251

could then be retracted back into the measuring instrument, and the calibration

target would be removed from the shield holder 110. This would place the

instrument in a condition ready for a patient or object measurement. The

measurement operation could be conducted such that light emitted from the nose

portion 104 of the instrument is reflected/scattered from the target object and is

detected by the instrument. Alternatively, the light head 251 could be used to

provide light for a measurement operation.

In some of the embodiments described above, a calibration operation has

relied on light that is reflected/scattered from, transmitted through or emitted by, a

portion of a calibration target having known optical properties. This could involve determining an amplitude of the reflected/scattered/transmitted/emitted light at one

or more wavelengths. In other devices and methods embodying the invention, the

radiation output to the calibration target could have a particular polarization

orientation. The measuring instrument could then be configured to determine a

polarization orientation of the reflected/scattered/transmitted/emitted light. Such

a method could rely on the relative attenuation of a polarized or depolarized

component of reflected/scattered/transmitted light, or an extent of depolarization.

Many variations could be made to the embodiments of the calibration targets

described above without departing from the spirit or scope of the present invention.

For instance, although each of the embodiments shown in the drawing figures have

a shield holder and a calibration/reference target that is generally circular or annular

in shape, any other shape could be used without departing from the invention. For

instance, the shield holder, infection shield and calibration target could be

rectangular, square, or any other shape necessary to conform to the shape of the

instrument to which the device is attached.

Also, the calibration layers of the embodiments described above could have

any type of optical, transmissive or fluorescent properties used to conduct a

calibration or reference operation. As mentioned above, use of the term "calibration

target" in the specification and claims is intended to encompass both calibration

targets and reference targets. Likewise, use of the term "calibration operation" is

intended to encompass both calibration and reference operations. In any one embodiment of the invention, the calibration layer would have

very specific reflective, transmissive and/or fluorescent properties. However,

calibration/reference targets embodying the invention might include different types

of calibration layers having different reflective/transmissive/fluorescent properties.

For instance, colored calibration targets could be provided in a variety of different

skin tones. A calibration device embodying the invention could then be selected by

a user based on a patient's skin tone or age, and the selected calibration target could

be used to calibrate an instrument.

Also, the reflective/transmissive/fluorescent properties of a calibration target

may be selected such that a measuring instrument can be calibrated/referenced at the

mean or the median of the expected measurement range. Such a strategy will provide

maximum measurement accuracy since any error is at a minimum for measurements

closest to the calibration value. For example, the reflectance of a calibration target

can be formulated such that its reflectance matches the median reflectance of the

patients expected to be measured with the instrument. As an additional example, the

fluorescence lifetime and/or quantum yield of a fluorescent target may be selected

such that it equals the median lifetime and/or quantum yield of the fluorescing

analyte being measured.

Also, although each of the embodiments described above have a user graspable

tab attached to the calibration layer, other types of user graspable tab configurations

are possible. For instance, instead of being a tab, a cord, a string or a ring of material could be attached to the calibration layer. For instance, in the embodiment shown

in Figure 18, the user graspable tab 202a is a loop of material whose ends are attached

to the calibration layer 200. Each of these items is easy for the finger of a user to

grasp and to pull. The invention is intended to include any type of user graspable

tab, cord, string, ring, or other device that can be used to remove the calibration layer

from the remaining portions of the device.

Furthermore, in the embodiments described above, an infection shield and a

calibration target are attached to a shield holder, which in turn is attached to the

instrument. Some embodiments of the device may not utilize a shield holder. In

these embodiments, the infection shield and/or the calibration target may be directly

attached to a measuring instrument. These embodiments may use an adhesive layer

or a mechanical attachment device to attach the infection shield and the calibration

target to the instrument.

Still further, if the instrument which the device is used with is not used for

medical purposes, and infection or cross-contamination is not an issue, a device

embodying the invention may simply comprise a calibration layer. The calibration

target in Figure 8 provides an example of such an embodiment. This calibration

target could be directly attached to the measuring instrument.

In yet another embodiment of the invention, a plurality of emitter and

detector pairs could be arranged in an array on a measuring instrument. During a

calibration operation using any of the calibration devices described above, the light output from the emitters could reflect/scatter from or be transmitted through

portions of the calibration device and impinge on the respective detectors. If a

fluorescent calibration target is used, fluorescent light from the target could impinge

on the detectors. After the calibration operation is conducted, the same

emitter/detector pairs could be used to interrogate multiple points on a target

material or tissue. Such a configuration would allow the measuring instrument to

develop an image of the target material or tissue, or an image of

reflective/transmissive/fluorescent properties of the target.

In still other embodiments, one or more light sources could illuminate/excite

a target material or tissue, and reflected/scattered/transmitted light, or fluorescent

light, passing from the target material or tissue could impinge on a detector array

configured generate an image of the material or tissue, or an image of the

reflective/transmissive/fluorescent properties of the target material or tissue. For

instance, a charged coupled device (CCD) could be used as the detector array. The

calibration devices described above could be used to calibrate or reference a

measuring instrument that utilizes such a detector array.

Figures 25A, 25B, and 25C show front, side and back views, respectively, of

a measurement system 803 embodying the invention. Figure 25D shows the

measurement system 803 in a charging stand 871. The elements in the measurement

system 803 which have similar counterparts in the previously discussed system 3, will

also have the earlier reference numbers indicated in parenthesis. The measurement system 803 includes a housing 843 which is sized so as to

be easily graspable by a human hand. A radiation analyzer 810 is coupled to the

calibration device 845 via one or more optical fibers 833 (see Figure 25B). A

calibration device 845 may be inserted into an opening end 846 of a cone-shaped

holder 858 of the housing 843. A curved portion 866 of the housing 843 allows the

user's hand to comfortably hold the measurement system 803.

Figure 8B shows a side view of the measurement system 803, including the

radiation analyzer 810 and a push button 861. The radiation analyzer 810 is mounted

on a printed circuit board (PCB) 818, which is powered by batteries 822. The

batteries 822 can be recharged when the system 803 is placed in a power adapter stand

through a charger connection 826. A liquid crystal display (LCD) device 832 is also

coupled to the PCB 818. An LCD device 832, which is visible through a window

841, displays measurement results, instructions, warnings, and other operating

information. The radiation analyzer 810 is controlled by a processor also mounted

on PCB 818.

Figures 25C and 25D show a back view of system 803, which includes back

portion 891 and the LCD device 832. A person can initiate a calibration, and then

a measurement, by pressing push button 861 with his or her thumb. In particular,

once a calibration measurement has been performed, the user graspable tab 280 (see

previous figures) is used to peel the calibration target 270 away from the window 260,

and the system 803 is ready to make a measurement on a patient. The LCD device 832 indicates when the measurement system 803 is ready to make a calibration

measurement, when a calibration measurement has been completed and the system

803 is ready to make an actual measurement, and when the system 803 has completed

a measurement. The LCD device 832 also displays the results of measurements, and

messages or other indicators. For instance, the LCD device 832 might show that a

particular calibration target 270 has already been used and that no additional

measurements can be made until a new calibration measurement is made.

A limit switch (not shown) may be installed at the end of the tip 858 to detect

the presence of a calibration device 45. Once the limit switch is engaged, a

calibration measurement is enabled and a measurement counter is initialized to zero.

Calibration is then performed to ready the device for taking a measurement. The

system software then increments the counter each time a measurement is made, up

to a predetermined maximum. Once the maximum number of measurements is

reached, the system software indicates that a calibration is again required, and the

device is prevented from taking additional measurements. Should the limit switch

be disengaged at any time in the measurement sequence, indicating the removal of the

disposable tip, the display indicates that a new calibration sequence must be begun

before other measurements may be taken. These software controls prevent an

operator from using one calibration target more than a predetermined number of

times before replacing the calibration device. Figure 25D shows a measurement system 803 with a charging stand 871 for

storing and charging the system 803. The charging stand 871 includes a center

portion 873 for receiving the system 803. The center portion 873 serves as both a

stand and a recharging unit. The stand 871 has an electrical cord (not shown) which

can be plugged into an outlet. The stand 871 also includes an electrical receiving unit

which receives charger connection 826 (see Figure 8B) of the system 803. An

indicator light 876 indicates when the measurement system 803 is properly placed in

the center portion 873 so that recharging may take place. The stand 871 further

includes a side receiving portion 875 which can be used to hold a supply 877 of

calibration devices 845.

A measuring instrument embodying the invention to transmit measurement

data directly from the instrument to a recording device via a wireless communication

system. The wireless communication system could be a radio link or infrared

communication link. Similarly, a charger stand for the measurement instrument

could receive measurement data and transmit the measurement data to a recording

device via a communication link.

Figure 26A is a schematic diagram of certain elements of a measurement

system 803, and in particular, of a radiation analyzer instrument 810. The radiation

analyzing instrument 810 includes an optical unit 914, a central processor unit (CPU)

905, and a memory 909. Figure 26B shows a perspective view of an optical unit 914

that includes an optical source 918, a detector array 923, an optical grating 951 and an output 955 which couples the optical unit 914 to the CPU 905 via a data bus 961.

The optical source 918 may be a tungsten halogen bulb, a noble gas filled tungsten

bulb or several LED's covering the desired regions of the optical spectrum. The

optical source 918 may also be placed at a location in the device housing to

illuminate the subject directly, without coupling the radiation into a fiber.

The embodiment shown in Figure 26B utilizes a microspectrometer offered

by American Laubscher Corporation of Farmingdale, LI, NY called the VIS/NIR

microspectrometer. Optical radiation 940 is output from optical source 918 and is

transmitted via fiber 833 to the target (not shown) to be measured. The return signal

941 travels back down optical fiber 833 and is output from fiber end 958 into a type

of waveguide 962 (cut away) and is incident on diffraction grating 951. Diffraction

grating 951 achieves self-focussing of radiation 941 to different points or detectors on

diode array 923, depending on the intensity and wavelengths of the return radiation

941.

The operation of system 803 will now be described in conjunction with

Figures 26A and 26B. First, a calibration target starts out being arranged on a

window of the measuring system, and a user pushes a button, which indicates that

a calibration measurement should be taken. Radiation 940 is emitted toward the

calibration target, which reflects at least a portion of the radiation back to the

measurement system. Because the calibration target has a known spectral

characteristic, the returned radiation 941 results in a detected intensity at individual detectors on the detector array 923, thereby yielding a measured calibration

characteristic. This measured calibration characteristic is compared to the expected

or known spectral characteristic of the calibration target, and a resulting adjustment

value (which could be an array of values) is determined. The calibration target is

then removed, and a measurement of tissue or material is made by outputting

radiation 940 as above. A resulting spectral characteristic is then output from

detector array 923, which in turn is adjusted by CPU 905 using the adjustment value

or characteristic to yield a calibrated spectral characteristic. The calibrated spectral

characteristic can then be used to determine some measurable characteristic of the

material or tissue. One such measurement is a non-intrusive bilirubin measurement

according to one embodiment of the invention, as will be discussed below.

Although a microspectrometer as shown in Figure 26B may be used in an

embodiment of the invention, other devices capable of measuring the amplitude of

radiation reflected from a patient's skin at different wavelengths can also be used.

For instance, Figure 31 shows a radiation analyzing device that includes a processor

905, a radiation source 918, radiation conduits 833, such as optical fibers, a memory

909 and a filter/detector unit 1000. The filter/detector unit may comprise a plurality

of detectors and filters. For instance, filters 1, 2 and 3 1010, 1020 and 1030, may be

designed to pass only discreet wavelengths of the radiation reflected from a patient's

skin. Each of the filters may be paired with a corresponding detector to determine

the amplitude of light reflected from a patient's skin at each of the three filter wavelengths. Alternatively, the filters may be successively coupled to a single

detector to determine the amplitude of the reflected light at each of the filter

wavelengths. In yet another embodiment, the filter/detector unit 1000 may comprise

a detector with a linear variable filter.

If the radiation conduits 833 of the device shown in Figure 31 comprise optical

fibers, the numerical aperture of the optical fibers can be selected to optimize the

efficiency of the device. For instance, the optical fibers used to transmit radiation

from the radiation source 918 to the patient's skin may have a numerical aperture

matched to the radiation source 918. In addition, the optical fibers used to transmit

light reflected from the patient's skin to the radiation analyzer may have a numerical

aperture matched to the radiation analyzer.

The optical fiber 833 of measurement device 803 may comprise one or a

plurality of fibers. Preferably, the optical fiber 833 comprises a plurality of fibers

arranged in a bundle. Figure 27 shows a bundle of optical fibers 333 which can be

used to transmit and receive radiation. The optical fibers are arranged so that they

approach a surface of a material or tissue 40 to be measured at an angle θ relative to

an axis perpendicular to the surface of the material or tissue 40. When the bundle of

optical fibers is inclined in this manner, backscattering effects are reduced. Angle θ

is preferably not 0° and sufficiently large to prevent backscattering effects. In one

embodiment, angle θ is between a few degrees and 20° and preferably between 5° and

10° and more preferably approximately 7°. Figure 28 shows the bundle of optical fibers 333 as seen from section line 28-28

of Figure 27. In the bundle of optical fibers 333, there is an outer ring of transmission

optical fibers 336, an inner ring of transmission fibers 337 and a central receive

optical fiber 335. When the device is in operation, radiation is transmitted through

the first and second rings of transmission fibers 336, 337, is reflected off the skin of

a patient, and received by the receive optical fiber 335.

Figure 29 shows the bundle of optical fibers as seen from section line 29-29 of

Figure 27. Because the ends of the optical fibers are cut at a slight angle, and because

the optical fibers themselves are cylindrical, the ends of the optical fibers appear to

be ovals in Figure 29.

Figure 30 shows a receive optical fiber 335 and four transmit optical fibers 336

and 337 surrounding the receive optical fiber 335. The receive optical fiber has a

smaller numerical aperture than the transmit optical fibers. The lines extending

down from the bottom of the optical fibers show the path that radiation would take

to leave or enter the optical fibers. For instance the area 335A shows the path that

radiation may take to enter the receive optical fiber 335. The areas marked 336A and

337A show the path that radiation may take when leaving a transmit optical fiber 336

and 337. Typically, the numerical aperture of the receive optical fiber 335 will be

smaller than the numerical aperture of the transmit optical fibers 336 and 337. Bilirubin Measurement Process

U.S. Patent No. 5,353,790, the contents of which are incorporated herein by

reference, presents a method and apparatus for determining bilirubin concentration

in human tissue such as skin. In particular, the patent discusses reflecting light from

the skin of a patient to determine a bilirubin concentration. The approach corrects

for maturity-dependent optical properties of the skin, including the amount of

melanin in the skin and the amount of blood in the skin. Reflected red to infrared

light is used to determine the maturity-dependent optical properties, reflected red

light is used to determine melanin content, and reflected yellow-orange light is used

to determine the amount of blood in the skin. These quantities are used, in

combination with reflected blue light, to calculate cutaneous bilirubin concentration.

U.S. Patent No. 5,353,790 discusses the absorption spectrum of melanin and

shows that the melanin absorption spectra essentially decreases linearly with

wavelength in the visible region. Moreover, since the melanin absorption varies

orders of magnitudes over the visible region, variations in skin pigmentation will

cause large absolute changes in the absorption at the shorter wavelengths, but the

same magnitude changes will cause relatively minuscule absolute changes in the very

long wavelengths (> 800 nm). The melanin pigmentation measured in the far red

wavelength range was found to have a pivot point at around 637 nm.

A measurement system embodying the invention and configured to detect a

bilirubin concentration in a patient takes advantage of the above phenomena and uses spectral reflectance to determine a serum bilirubin level in mg/dL (milligrams of

bilirubin per deciliters of blood), as will now be discussed. Figure 32 shows a

flowchart setting forth the steps of a first method embodying the invention that may

be used by a measurement system to perform bilirubin measurements on a patient.

The steps performed are an improved version of the approach discussed in U.S.

Patent No. 5,353,790. Step 702 involves performing a calibration measurement in a

manner similar to that described above. This involves simply outputting radiation

to a calibration target, and measuring the return signal (which could be

reflected/scattered/transmitted/ flourescent light). The calibration measurement

yields a measured calibration spectrum, which is compared to an expected calibration

spectrum (which in turn, depends on the calibration target). The difference between

the expected or known spectrum and the measured spectrum serves as the calibration

data. The calibration data is used to modify actual measured data, thereby

compensating for unit to unit and time varying changes in source luminosity,

delivery optics, collection optics, detection sensitivity, electronic drift, and

environmental conditions such as temperature and humidity.

Step 704 involves making a measurement of a patient's skin by illuminating

the skin with light and detecting a frequency spectrum of light reflected from the

patient's skin. Step 708 involves converting the reflection (scattering) measurements

into an optical density. Step 712 then involves calculating, from a first portion of the

spectrum, a first parameter indicative of a maturity of the skin. Step 716 involves calculating, from a second portion of the spectrum, a second parameter indicative of

an amount of melanin in the skin. Step 720 involves calculating, from a third portion

of the spectrum, a third parameter indicative of a blood content of the skin. Step 724

involves calculating, from a fourth portion of the spectrum, a fourth parameter

indicative of an uncorrected bilirubin concentration in the skin. Step 728 involves

calculating a corrected bilirubin concentration in the skin as a function of the first,

second, third and fourth parameters.

Figure 33 shows the results of data taken using the method illustrated in Figure

32, versus a standard serum bilirubin (heel stick) method. The subjects were 72 full

term babies of varied ethnic background, with 20 African Americans, 2 Hispanic

Americans, 48 white Americans, and 2 Asian Americans. "R" represents the

correlation coefficient between the measurement method described in Figure 32,

versus the standard method of serum bilirubin. The correlation coefficient shown

is 0.9165 with a perfect correlation given as 1.0000. The tests represent a purely

prospective application of the method illustrated in Figure 32.

Figure 34 shows a flowchart setting forth the steps of another method

embodying the invention for measuring a bilirubin concentration of a patient. This

second method is a more simplified method compared to the method described

above. In step 1805 the measurement system first makes a calibration measurement

as described above. Next, in step 1810, a measurement is made using a first portion

of the spectrum to determine an amplitude of the reflected light at a first wavelength. Next, in step 1815, a measurement is made at a second portion of the spectrum to

determine an amplitude of light at a second wavelength. The first and second

wavelengths are indicative of the blood content of the patient's skin. In step 1820,

a third measurement is made to determine the amplitude of the reflective light at a

third wavelength indicative of an uncorrected bilirubin score. In step 1825, a CPU

of the measurement device calculates a calibrated and corrected bilirubin

concentration using the results of steps 1805 through 1820.

The significance of making measurements at the first and second wavelengths

will now be explained with reference to Figure 35. Figure 35 illustrates two lines, L3

and L4, that represent the amplitude of light reflected from a patient's skin under two

different conditions. In a first condition, the blood flowing through the patient's

skin is fully oxygenated. In the second condition, the blood flowing through the

patient's skin has no oxygen attached to the hemoglobin in the blood. As shown in

Figure 35, lines L3 and L4 cross one another at two points H and I. Experimental

results have indicated that the wavelengths corresponding to points H and I are at

approximately 526 and 585 nanometers, respectively.

By making the measurements of the amplitude of light reflected from a

patient's skin at approximately 526 nanometers and 586 nanometers, it is possible to

obtain a measurement representative of the blood content of the patient's skin.

Because the measurements are made at the crossover points, it does not matter

whether the blood in the patient's skin is fully or partially oxygenated. The method of calculating a calibrated and corrected bilirubin concentration

of Figure 34 will now be further explained with reference to Figure 36. In Figure 36,

L5 represents an amplitude of light reflected from a patient's skin at various

wavelengths.

The amplitude of light reflected from a patient's skin at a first wavelength, as

measured in step 1810, is taken at a wavelength of approximately 526 nanometers.

The amplitude at this wavelength is represented by point B in Figure 16. The

amplitude of the light reflected from the patient's skin at the second wavelength is

taken at approximately 586 nanometers, which is represented by point C in Figure

36. An imaginary line Ll is drawn through points B and C and backwards through

smaller wavelengths of the visible light spectrum. The amplitude value at the

intersection of the line Ll and an imaginary line at 476 nanometers is then

determined, which is represented by point D in Figure 36. Point A in Figure 36

represents the measured amplitude of the light reflected from the patient's skin at 476

nanometers. The value of point D is then subtracted from the value of point A to

determine a corrected bilirubin score. This corrected bilirubin score is then used

with the calibration data taken during a calibration measurement to determine a

calibrated and corrected bilirubin concentration of the patient's skin.

The second method described above is far more simple than the first method,

as it only involves taking amplitude measurements of reflected light at three discreet

wavelengths. Experimental results have shown that the second method provides substantially the same level of accuracy as the first method, and in some cases the

second method produces even better results.

A third method of determining a bilirubin concentration in a patient's skin

will now be described with reference to Figure 37. Figure 37 shows a flowchart of

the steps of a third method of determining a patient's bilirubin concentration. In

step 1905, a calibration measurement is taken as described above. In step 1910,

measurements of the amplitude of light reflected from a patient's skin are made at

first, second, third, fourth and fifth wavelengths. In step 1915, the first, second and

third measurements are adjusted based on the fourth and fifth measurements. In step

1920, a calibrated and corrected bilirubin concentration is calculated using the

calibration measurement and the adjusted first, second and third measurements.

The first, second and third measurements taken during step 1910 are taken at

the wavelengths 486 nanometers, 526 nanometers, and 586 nanometers as described

above in connection with the second method. The fourth and fifth measurements

are taken at wavelengths J and K, as shown in Figure 36, which are represented by

the points M and N. The wavelengths corresponding to J and K are in the range

between 600 and 700 nanometers. The amplitude of the light reflected from the

patient's skin at frequencies J and K are representative of melanin in the patient's

skin. A line drawn through points J and K will have a negative slope that indicates

the amount of melanin in the patient's skin. The greater than negative slope (or the more steeply the line is inclined down toward the right) the greater the amount of

melanin.

In step 1915, the first, second and third measurements are adjusted based on

the fourth and fifth measurements. To accomplish this adjustment, a line L2 is

drawn through points M and N, and the line L2 is projected backwards through the

smaller wavelengths, as shown in Figure 36. Points of intersection of the line L2

with imaginary lines at the first, second and third wavelengths are determined. These

points are shown as points E, F and G in Figure 36. The amplitude values of points

E, F and G are then subtracted from the respective measurements made at these

wavelengths, which are shown as points C, B and A. These adjusted measurements

for the first, second and third wavelengths are then used to determine a calibrated and

corrected bilirubin concentration for the patient according to the methods described

above.

The above-described process calls for a single measurement to be made on a

single location on a patient's skin. A measuring device embodying the invention

could be configured to take a plurality of measurements on the same portion of the

patient's body, or at different portions of the patient's body and to average the

measurements to create a final measurement result. Also, if a plurality of

measurements are taken, one or more of the measurements having the greatest

deviation may be discarded, and an average of a lesser number of measurements may

be created to arrive at a final measurement result. Further, if the deviation between a plurality of measurements exceeds a predetermined standard deviation, the entire

set of measurements may be discarded, and a new set of measurements may be

obtained.

Many alternatives and modifications of the above examples would be

apparent to those skilled in the art upon reading the foregoing or practicing the

invention. The apparatus and methods described above are intended to be exemplary

and are not intended to limit the scope of the invention as defined by the following

claims.

Claims

WHAT IS CLAIMED IS:

1. A disposable calibration device, comprising:

a double-sided adhesive layer, wherein an adhesive strength on a first

side of the adhesive layer is greater than an adhesive strength on a second side of the

adhesive layer; and

a calibration target arranged on at least one side of the adhesive layer.

2. The device of claim 1, wherein the calibration target is arranged on the

first side of the adhesive layer.

3. The device of claim 1, wherein the calibration target includes a user

graspable tab.

4. The device of claim 1, wherein the calibration target includes a reduced

strength portion, and wherein the calibration target will tear or separate along the

reduced strength portion when the calibration target is separated from other portions

of the calibration device.

5. The device of claim 4, wherein the reduced strength portion comprises

at least one of a slit, a perforation, and a crease.

6. The device of claim 1, wherein the calibration target is configured such

that the calibration target will tear or separate in a predetermined manner when the

calibration target is removed from other portions of the calibration device.

7. The device of claim 1, further comprising a cutter for causing the

calibration target to tear or separate in a predetermined manner when the calibration

target is removed from other portions of the calibration device.

8. The device of claim 7, wherein the cutter comprises one of a wire or a

monofilament.

9. The device of claim 1, wherein the double-sided adhesive layer extends

around all but a portion of a peripheral edge of the calibration target.

10. The device of claim 1, wherein the calibration target includes a

calibration portion having properties that are usable for calibration or reference of

an instrument to which the calibration device is attached.

11. The device of claim 10, wherein the calibration target further comprises

a reduced strength portion that is configured so that the calibration target tears or

separates across the calibration portion when the calibration target is removed from

other portions of the calibration device.

12. The device of claim 11, wherein the adhesive layer extends around all

but a selected portion of a periphery of the calibration target, and wherein the

calibration target and the adhesive layer are oriented with respect to one another so

that the adhesive layer aids tearing or separation of the calibration target when the

calibration target is removed from other portions of the calibration device.

13. The device of claim 1, further comprising a shield layer arranged on a

side of the double-sided adhesive layer opposite the calibration target.

14. The device of claim 13, wherein the double-sided adhesive layer

comprises a first double adhesive layer, and further comprising a second double

adhesive layer arranged on a side of the shield layer opposite the double-sided

adhesive layer.

15. The device of claim 14, further comprising a calibration device holder

that is attachable to a measuring instrument, wherein the second double-sided

adhesive layer attaches the shield layer to the calibration device holder.

16. The device of claim 1, further comprising a calibration device holder

that is attachable to a measuring instrument, wherein the double-sided adhesive layer

and the calibration target are removably attached to the calibration device holder.

17. The device of claim 16, wherein the calibration device holder includes

a shield layer.

18. A disposable calibration device, comprising:

a calibration layer; and

means for attaching the calibration layer to a measuring instrument,

wherein the device is configured such that the calibration layer will tear or separate

in a predetermined manner when the calibration layer is removed from the

measuring instrument.

19. The device of claim 18, wherein the calibration layer includes a reduced

strength portion that causes the calibration layer to tear or separate in a

predetermined manner when the calibration layer is removed from the measuring

instrument.

20. A calibration device, comprising:

a structure, through which radiation can pass; and

a removable calibration target arranged on said opening, wherein the

removable calibration target includes a fluorescent portion.

21. The calibration device of claim 20, further comprising an adhesive

portion configured to adhere the removable calibration target to a measuring

instrument.

22. The calibration device of claim 20, wherein the removable calibration

target includes at least one reduced strength portion configured such that the

removable calibration target will tear or separate along the at least one reduced

strength portion when the removable calibration target is removed from other

portions of the calibration device.

23. The calibration target of claim 20, further comprising a shield layer

attached to the structure.

24. The calibration target of claim 23, wherein the shield layer is arranged

on the structure such that when the calibration target is removed from the structure,

the shield layer remains attached to the structure.

25. A calibration device, comprising:

a structure, through which radiation can pass; and

a removable calibration target arranged on said opening, wherein the

removable calibration target includes a transmissive portion configured to allow a

measurement instrument to conduct a calibration operation using radiation that is

transmitted through the calibration target.

26. The calibration device of claim 25, wherein the structure comprises an

adhesive portion configured to adhere the removable calibration target to a

measuring instrument to which the calibration device is attached.

27. The calibration device of claim 25, wherein the removable calibration

target includes at least one reduced strength portion configured such that the

removable calibration target will tear or separate along the at least one reduced strength portion when the removable calibration target is removed from other

portions of the calibration device.

28. The calibration target of claim 25, further comprising a shield layer

attached to the structure.

29. The calibration target of claim 28, wherein the shield layer is arranged

the shield layer remains attached to the structure.

30. A calibration device, comprising:

a calibration target holder configured to be arranged on a measuring

instrument; and

a calibration target having known optical properties that is mountable

on the holder.

31. The calibration device of claim 30, wherein the calibration target holder

is configured to block external light from reaching a detector of a measuring

instrument when the holder is arranged on a measuring instrument.

32. The calibration device of claim 30, further comprising a shield layer,

wherein the calibration device is configured such that when the calibration device is

arranged on a measuring instrument, and the calibration target is removed, the shield

layer remains attached to the measuring instrument.

33. A calibration device for calibrating a measuring system that transmits

radiation to a material or tissue from an output end to effect measurements,

comprising:

a removable calibration target;

a structure for holding the removable calibration target, the structure

including an opening through which radiation can be transmitted; and

an index matching agent for interposition between the output end of

the measuring system and the material or tissue being measured.

34. The calibration device of claim 33, wherein the index matching agent

comprises a window of a soft polymer that is attached to the structure.

35. The calibration device of claim 33, wherein a substance held within the

structure acts an index matching agent between the output end of the measuring

system and the removable calibration target while the calibration target is attached

to the structure, and wherein the substance acts as an index matching agent between the output end of the measuring system and a material or tissue being measured when

the removable calibration target is removed.

36. A method of calibrating a measuring instrument, comprising the steps

of:

arranging a fluorescent calibration device on a measuring instrument;

conducting a calibration measurement using the fluorescent calibration

device; and

removing at least a portion of the fluorescent calibration device from

the measuring instrument.

37. The method of claim 36, wherein the removing step comprises leaving

a structure of the fluorescent calibration device attached to the measuring instrument

such that radiation can pass through the structure during a subsequent measuring

operation.

38. The method of claim 36, wherein the step of conducting a calibration

measurement comprises the steps of:

illuminating a fluorescent calibration target of the calibration device

with electromagnetic radiation; and measuring electromagnetic radiation passing from the fluorescent

calibration target to the measuring instrument.

39. The method of claim 38, wherein the illuminating step comprises

illuminating the fluorescent calibration target with electromagnetic radiation having

a first wavelength range, wherein the measuring step comprises measuring

electromagnetic radiation having a second wavelength range, and wherein the first

and second wavelength ranges are not co-extensive.

40. The method of claim 38, wherein the measuring step comprises

measuring fluorescent electromagnetic radiation generated by the fluorescent

calibration target.

41. The method of claim 40, wherein the measuring step further comprises

measuring radiation that is scattered from the calibration target.

42. The method of claim 40, wherein the measuring step comprises

measuring a time characteristic of the fluorescent electromagnetic radiation.

43. The method of claim 40, wherein the measuring step comprises

measuring a polarization characteristic of the fluorescent electromagnetic radiation.

44. The method of claim 38, wherein the illuminating step comprises

illuminating the fluorescent calibration target with a burst of electromagnetic

radiation, and wherein the measuring step comprises measuring an amount of time

required for fluorescent electromagnetic radiation produced by the fluorescent

calibration target in response to the burst of illuminating electromagnetic radiation

to decay below a threshold value.

45. The method of claim 36, wherein the step of conducting a calibration

measurement comprises the steps of:

illuminating the fluorescent calibration device with amplitude

modulated electromagnetic radiation;

measuring electromagnetic radiation passing from the fluorescent

calibration device to the measuring instrument; and

determining a phase shift between the illuminating amplitude

modulated electromagnetic radiation and the electromagnetic radiation passing from

the fluorescent calibration device to the measuring instrument.

46. The method of claim 45, wherein the measuring step comprises

measuring fluorescent electromagnetic radiation generated by a fluorescent

calibration target of the fluorescent calibration device.

47. The method of claim 45, further comprises a step of determining a

demodulation factor, wherein the demodulation factor represents a ratio of

amplitudes of the illuminating electromagnetic radiation and the electromagnetic

radiation passing from the fluorescent calibration device to the measuring

instrument.

48. The method of claim 36, wherein the step of conducting a calibration

measurement comprises the steps of:

illuminating the fluorescent calibration device with polarized

electromagnetic radiation;

measuring electromagnetic radiation passing from the fluorescent

calibration device to the measuring instrument; and

determining a polarization difference between the illuminating

electromagnetic radiation and the electromagnetic radiation passing from the

fluorescent calibration device to the measuring instrument.

49. A method of calibrating a measuring instrument, comprising the steps

of:

placing a transmissive calibration device over an output end of a

measuring instrument; conducting a calibration operation using the transmissive calibration

device; and

removing at least a portion of the transmissive calibration device from

the measuring instrument.

50. The method of claim 49, wherein the removing step comprises leaving

a structure of the transmissive calibration device attached to the measuring

instrument such that radiation can pass through the structure during a subsequent

measuring operation.

51. The method of claim 49, wherein the step of conducting a calibration

operation comprises the steps of:

illuminating a portion of the transmissive calibration device with

electromagnetic radiation; and

measuring electromagnetic radiation passing through the transmissive

calibration device.

52. The method of claim 51, wherein the illuminating step comprises

illuminating a portion of the transmissive calibration device with electromagnetic

radiation generated by the measuring instrument.

53. The method of claim 51, wherein the illuminating step comprises

radiation generated by a source external to the measuring instrument.

54. A method of conducting a calibration operation, comprising the steps

of:

arranging a calibration device on a measuring instrument, wherein the

calibration device includes a calibration target, and wherein a portion of the

calibration target has predetermined optical properties;

conducting a calibration operation using the calibration target; and

removing the calibration target from the calibration device such that the

portion of the calibration target having predetermined optical properties is

irrevocably altered.

55. The method of claim 54, wherein the removing step comprises at least

partially destroying the portion of the calibration target having known optical

properties.

56. The method of claim 54, wherein the removing step comprises

removing the calibration target such that the calibration target tears or separates

along a reduced strength portion.

57. A method of measuring an optical property, comprising the steps of:

attaching a reference target to a measuring instrument;

conducting at least one reference measurement on the reference target

to determine a reference value;

conducting at least one object measurement on an object to determine

an object value; and

calculating an optical property of the object based on a relationship

between the object value and the reference value.

58. The method of claim 57, wherein the step of conducting at least one

reference measurement comprises:

conducting a measurement on the reference target with a light source

of the measuring instrument turned off to obtain a dark reference reading;

conducting a measurement on the reference target with the light source

of the measuring instrument turned on to obtain a reference reading; and

subtracting the dark reference reading from the reference reading to

obtain the reference value.

59. The method of claim 57, wherein the step of conducting at least one

object measurement comprises: conducting a measurement on an object with a light source of the

measuring instrument turned off to obtain a dark object reading;

conducting a measurement on the object with a light source of the

measuring instrument turned on to obtain an object reading; and

subtracting the dark object reading from the object reading to obtain

the object value.

60. The method of claim 57, wherein the step of calculating an optical

property comprises calculating a logarithm of a ratio of the object value to the

reference value.

61. The method of claim 57, wherein the step of conducting a reference

measurement and the step of conducting an object measurement both comprise

correcting for stray light.

62. A method of measuring a condition of a target object with a device that

outputs radiation from a distal end of the device, comprising the steps of:

applying an index matching agent to one of the target object and the

distal end of the device;

emitting radiation from the distal end of the device so that the radiation

passes through the index matching agent to the target object; receiving radiation passing from the target object to the distal end of the

device; and

analyzing the received radiation to determine a condition of the target

object.

63. The method of claim 62, further comprising the step of conducting a

calibration measurement on a calibration target and storing resulting calibration data

prior to performing the emitting step.

64. The method of claim 63, wherein the step of conducting a calibration

measurement comprises the steps of:

emitting radiation from the distal end of the device toward the

calibration target;

receiving radiation passing from the calibration target to the distal end

of the device; and

calculating calibration data based on the received radiation.

65. The method of claim 63, wherein the step of applying an index

matching agent is performed before the calibration measurement is performed.

66. A method for determining a bilirubin concentration of a patient,

comprising the steps of:

a) illuminating a portion of a skin of the patient with light;

b) detecting a frequency spectrum of light scattered from the skin;

c) determining, from first and second portions of the spectrum, a

first parameter indicative of a blood oxygen content of the skin;

d) determining, from a third portion of the spectrum, a second

parameter indicative of an uncorrected bilirubin concentration; and

e) calculating a corrected bilirubin concentration based on the first

and second parameters.

67. The method of claim 66, further comprising the step of performing a

prior to illuminating the patient's skin with light, wherein the step of calculating a

corrected bilirubin concentration is also based on the calibration data.

68. The method of claim 66, wherein the first and second portions of the

spectrum are at approximately 520nm and 585nm, respectively.

69. The method of claim 68, wherein the third portion of the spectrum is

at approximately 476nm.

70. The method of claim 66, wherein the third portion of the spectrum is

at approximately 476nm.

71. The method of claim 66, wherein the performance of steps a-e result in

a first corrected bilirubin concentration, and further comprising the steps of:

f) repeating steps a-e to calculate a second corrected bilirubin

concentration; and

g) calculating an average corrected bilirubin concentration based on

the first and second corrected bilirubin concentrations.

72. The method of claim 71, wherein different portions of the patient's skin

are illuminated each time steps a-e are performed.

73. The method of claim 72, wherein the different portions of the patient's

skin are located on different portions of the patient's body.

74. The method of claim 66, wherein the performance of steps a-e result in

a first corrected bilirubin concentration, further comprising the steps of:

f) repeating steps a-e at least twice to calculate at least second and

third corrected bilirubin concentrations; g) calculating an average corrected bilirubin concentration and a

standard deviation using at least the first, second and third corrected bilirubin

concentrations;

h) comparing the calculated standard deviation to a predetermined

maximum standard deviation; and

i) repeating steps a-g if the calculated standard deviation exceeds the

predetermined maximum standard deviation.

75. A system for determining a bilirubin concentration in a patient,

comprising:

means for illuminating a portion of the patient's skin with light;

means for detecting a frequency spectrum of light scattered from the

patient's skin;

means for determining, from first and second portions of the spectrum,

a first parameter indicative of a blood content of the skin;

means for determining, from a third portion of the spectrum, a second

parameter indicative of an uncorrected bilirubin concentration; and

means for calculating a corrected bilirubin concentration based on the

first and second parameters.

76. The system of claim 75, further comprising means for performing a

calibration measurement on a calibration target and for storing resulting calibration

data, wherein the means for calculating a corrected bilirubin concentration also

utilizes the calibration data.

77. The system of claim 75, further comprising:

means for calculating an average corrected bilirubin concentration and

a standard deviation using at least three calculated corrected bilirubin concentrations;

and

means for comparing the calculated standard deviation to a

predetermined maximum standard deviation.

78. A system for measuring a bilirubin concentration of a patient,

comprising:

a radiation analyzing device for analyzing radiation scattered or

reflected from a patient's skin, and for outputting radiation data;

a radiation source;

at least one radiation transmitting conduit for conducting radiation

from the radiation source to a portion of the patient's skin;

at least one radiation receiving conduit for conducting radiation

scattered from the patient's skin to the radiation analyzing device; and means for calculating a bilirubin concentration of the patient based on

an amplitude of the reflected or scattered radiation at first and second wavelengths

indicative of a blood content of the patient's skin and on an amplitude of the

reflected or scattered radiation at a third wavelength indicative of a bilirubin

concentration in the mammal's skin.

79. The system of claim 78, wherein the at least one radiation transmitting

conduit directs radiation at the patient's skin at an angle relative to an axis

perpendicular to the skin surface, and wherein the angle is large enough to reduce

radiation backscattering.

80. The system of claim 78, further comprising a window located between

the radiation transmitting and receiving conduits and an exterior measuring end of

the system, wherein the window comprises a soft polymer that acts as an index

matching agent between the radiation transmitting and receiving conduits and the

patient's skin.

81. The system of claim 78, wherein the radiation analyzing device

comprises a spectrometer.

82. The system of claim 78, wherein the radiation analyzing device

comprises a diffraction grating and a plurality of detectors, wherein the diffraction

grating focuses radiation having predetermined wavelengths on respective ones of the

plurality of detectors.

83. The system of claim 78, wherein the radiation analyzing device

comprises at least one radiation detector and a plurality of radiation filters, each of

the plurality of radiation filters allowing only a narrow wavelength band of radiation

to reach the at least one radiation detector.

84. A method for determining a bilirubin concentration of a patient,

comprising the steps of:

a) illuminating a portion of a skin of the patient with light;

b) detecting a frequency spectrum of light scattered from the skin;

c) determining, from first and second portions of the spectrum, a

first parameter indicative of a blood oxygen content of the skin;

d) determining, from third and fourth portions of the spectrum, a

second parameter indicative of a melanin content of the skin;

e) determining, from a fifth portion of the spectrum, a third

parameter indicative of an uncorrected bilirubin concentration; and f) calculating a corrected bilirubin concentration based on the first,

second and third parameters.

85. The method of claim 84, further comprising the step of performing a

corrected bilirubin concentration is also based on the calibration data.

86. The method of claim 84, wherein the first and second portions of the

spectrum are at approximately 526nm and 586nm, respectively.

87. The method of claim 84, wherein the fifth portion of the spectrum is

at approximately 476nm.

88. The method of claim 84, wherein the third and fourth portions of the

spectrum are between approximately 600nm and approximately 700nm.