CA1139124A - Apparatus for measurement of blood bilirubin concentration - Google Patents

Apparatus for measurement of blood bilirubin concentration

Info

Publication number
CA1139124A
CA1139124A CA000350046A CA350046A CA1139124A CA 1139124 A CA1139124 A CA 1139124A CA 000350046 A CA000350046 A CA 000350046A CA 350046 A CA350046 A CA 350046A CA 1139124 A CA1139124 A CA 1139124A
Authority
CA
Canada
Prior art keywords
sample
test
light
optical axis
sample holder
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
CA000350046A
Other languages
French (fr)
Inventor
Julius S. Rosen
Robert J. Meltzer
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Warner Lambert Technologies Inc
Original Assignee
Warner Lambert Technologies Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Warner Lambert Technologies Inc filed Critical Warner Lambert Technologies Inc
Application granted granted Critical
Publication of CA1139124A publication Critical patent/CA1139124A/en
Expired legal-status Critical Current

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Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/314Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry with comparison of measurements at specific and non-specific wavelengths
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/72Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood pigments, e.g. haemoglobin, bilirubin or other porphyrins; involving occult blood
    • G01N33/728Bilirubin; including biliverdin

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Engineering & Computer Science (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Immunology (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Pathology (AREA)
  • General Physics & Mathematics (AREA)
  • General Health & Medical Sciences (AREA)
  • Food Science & Technology (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

Abstract of the Disclosure Electro-optical system to test for bilirubin presence and concentration in blood samples. An optical system for transilluminating the blood sample with a beam divider to create parallel optical paths after transmission through the sample. A different band pass filter in each of the parallel paths provides transmitted light at two specific wavelengths such that the effect of hemoglobin, in the sample, on the compared light intensities along the parallel paths is eliminated.
A gradient density filter in one path is movable, in response to an imbalance, to a position at which intensities of light transmitted along the parallel paths are equal. The filter position is correlated to a reading of bilirubin concentration.
An automated sample handling system receives samples, moves them into operative position in the optical system and signals the optical system to function, and returns the sample for removal.

Description

~l~3~
APPARATUS FOR MEASUREM~NT OF
B OOD BILIRUBIN CONCENTR~TION

sackground of the Invention This invention relates -to testing of blood serum samples for measuremen-t of bilirubin concentration. More par-ticularLy, the invention is a novel apparatus for performing such measurement.
The general testing method used herein involves directing a beam of light through a blood sample, then along parallel optical paths through a narrow band pass fi:Lter, ~60 nm in one path and 550 nm in the other path, then to compare the light trans-mittance or attenuation in the two optical paths as an indication of bilirubin concentration in the blood sample. This method is more fully described in United States Patent ~3569721 to Goldberg and Polanyi.
Goldbery and Polanyi also disclose an apparatus for performing their test method. I-t is an optical system including light source and condenser Eor transilluminating a blood sample, collimating optics for light transmitted by the sample, and a beam divider to create parallel optical paths. A 461 nm band pass filter in one path and a 551 nm band pass filter in the other path transmit light to respective photodetectors which are in turn connected to a galvonometer to indicate balance or imbalance of the intensity of light transmitted along the two optical paths.
A variable aperature in the path of light to the 551 nm filter adjustably attenuates the light transmission in that path. This variable aperture is calibrated to indicate bilirubin concentration when its setting is such that the galvonometer is at a null condition. Adjustment of the variable aperture to reach a null condition is manual.

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Summary of the Invention It is an object of the present invention to provide a bilirubin measurement apparatus to perform ~he general bilirubin test method described and which operates auto-matieally to reaeh a null condition for a readout.
Briefly, the present invention can be summarized as an eleetro-optieal system including light source and condenser for transilluminating a blood sample, collimating optics for light transmitted by the sample, and a beam divider to create parallel optical paths. A 460 nm band pass filter is in one optieal path whieh then leads to a first photo detector, in turn operatively eonneeted by suitable eireuitry to a motor. A 550 nm band pass filter is in the other optical path from the beam divider whieh path then leads to a second photo detector, in turn operatively conneeted by suitable circuitry to the same motor.
movable gradient density filter or optical wedge in the path of the 550 nm filter is operatively eonnected to-the motor and movable by the motor to a position in the light path to achieve a null eondition when light intensity at both photo deteetors is in balance. The null position of the optieal wedge is eorrelated to a readin~ of bilirubin coneentration in the sample.
In a more specific aspect the invention provides a system for measuring the concentration of bilirubin in a test sample of blood serum, including: a light source to direct light along an optical axis to illuminate a test station, a sample handling system for presentation of test samples of blood serum at the test station, the sample holding system ineluding, a sample holder adapted to hold a blood sample placed thereon and movable relative to the optical axis in a defined locus cb/ - -be~ween a reference position in which the sample is out of the optical axis, ~nd a -test position in which the sample is on the optical axis at the tes-t station, and the sample holder forming a reference aperture and a test aperture which are sequentially positioned at the test station when the sample holder is at its r.eference and test positions respectively, an objective lens to project light further àlong the optical axis from the test . station, a beam divider disp~sed on the optical axis to receive light Erom the objective lens and to partially reflect and partially transmit same along parallel optical paths, a band pass filter in each of the parallel optical paths to transmit substantially only light of one wavelength, a photodetector behind the band pass filter in each of the parallel optical paths to receive.
light trc~nsmitted thereby, an adjustable light attenuator in one oE the parallel optical paths for adjustably varyin~ the intensity of light trans-mitted therethrough to the associated ~hotodetector, the photodet.ectors electrically connected to a carriage motor which is responsive to any i~balance `. in the signals from the photodetectors to move the li.ght attenuator to a position at which the photodetector signals to the motor.are in balance, the resulting position of the light attenuator being correlated to bilirubin concentration in the test sample.
The det~ils, operation and benefits of the present invention, will now be described more s~ecifically with reference to the accompanying drawing.
' '~
Figure 1 is a plan view of the system of this invention, partly in section.
Figure 2 is a sectional elevation taken along the line II-II
of Figure 1.
Figure 3 is a detail elevation taken along the line III-III of . Figure 1.
Figure 4 is an eleva-tion view of a detail of the sysbem.
-2a-~ - -3-~ ~ 39t~

Figure ~ is a sectional plan view of the dPtail of Figure 4, taken along the line V-V o~ Figure 4.
Description Figure t shows the system of this invention, in plan view, supported on a frame generally indicated at 2. A light source 4, a condenser lens 6, a ~irst re~lector 8, a second reflector 10, and an objective lens 12 are disposed on an optical axis 14. From objective lens 12 onward, the optical system is best seen with reference also to Figure 2 and in-cludes a beam divider 16 which divides the optical axis 14 into parallel optical paths 14r and 14t. The term "parallel"
is used herein to describe optical paths in the same sense as "parallel" electric circuits and the like, and not in the geo-metric sense to denote spatial parallelism.
Beam divider 16 is shown in Figure 2 supported by, and depending from, frame 2 which is actually above the system, all the elements described han0 from frame 2 above. The r~
ected optical path 14r leads ~rom beam divider ~6 through a 460 nm band pass filter 18 to a first photo detector 20. Trans-mitted optical path 14t leads rom beam divider 16 through a 550 nm band pass filter 22 to a second photo detector 24.
A pair of parallel guide rails 26 are stationarily mounted to the frame 2 and extend forward and back to slidably support a carriage member 28 thereon. Carriage member 28 is mounted for æliding back and forth, in the directions indicated, on rails 26 by suitable Y-blocks or the like at 30, Carriage member 28 carries an optical filter wedge 32 for movement of wedge 32 relative to the optical path 14t. Wedge 32 is, in essence, a filter elemen. having a gradient density from one end to the other so that by moving it a~ross the optical path 14t, transmission along path 14t is varied. Wedge 32 is cali-brated from end to end so that its lateral position relative to the optical path 14t is correlated to its light attenuation at that position.

''11 `

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Carriage 28 is connected at 34 to a drive beltlwhich in turn is mounted on suitable pulleys 38 and connected by a drive pulley 39 to a carriage drive motor 40. Motor 40 is a reversible stepper motor, operatively connected to the elec-trical outputs from photo detectors 20 and 24 so that an im-balance in the signals from the two photo detectors 20 and 24 signals the motor 40 to move carriage 28 and optical wedge 32 to a null position in which the equal or balanced signals from the photo detectors mean that light intensities through the 460 nm filter and the 550 nm filter are equal~ A normally closed limit switch 42 is frame-mounted and positioned in the way of the travel of carriage 28 at each end point of its tra-vel. As an equipment protective measure, when either switch 42 is abutted by the carriage 28, the drive circuit is broken and motor and carriage stopped. Switches 42 are electrically connected to the motor 40 though this is not shown in the drawing.
A blood sample handling system is also shown in Figure 1 and is mounted to framè 2. A sample drive motor 50, which is a reversible stepper motor, is operatively connected at its output shaft 52 to a sample holder shaft 54 which extends through and is supported for rotation by a housing 56. A sam-ple holder assembly 58 is fastened for rotation on shaft 54.
Sample holder 58 is shown in detail in Figures 4 and 5. The end of shaft 54 supports a cam 6Q which is operatively connec-ted to a limit switch 62 which is in turn electrically connec-ted to sample drive motor 50. The cam 60, limit switch 62 interaction can be more clearly seen in Figure 3 in which the switch 62 is open and the sample drive motor 50 therefore op-erative. Housing 56 includes a pair of apertures 64 to trans-mit light along the optical axis 14.
The sample holder assembly is shown in a rest or refer-ence position to receive a blood sample. In this position, a re~erence aperture 66 in the holder assembl~ is in line with . , .

~ ~.3~

apertures 64 of the housing and passes lightr unmodified by a blood sample, from the light source 4 to the photo detectors 20 and 24~ This permits calibration, or a check on calibra-tion, of the instrument prior to every actual blood sample S measurement.
Referring now to Figures 4 and 5 particularly, sample holder 58 includes a sample insert/re val station 68 in which a blood sample, typically between two glass plates, is placed and held by leaf springs 70. The sample holder includes a sample test aperture 72 positioned to direct light through the blood sample when it is in place. Sample holder 58 is rotatable 90 on shaft 54 to move a blood sample rom its insert/remo~al position shown to its test position in which the test aperture 72 is where reference aperture 66 is now lS shown, i.e. on the optical axis 14. Sample drive motor 50 is connected to a detent switch 74 which coacts with the sam-ple holder 58 to seat (and thereby close the switch) at each end of the 90 arc travel of the holder 58.
The operation of the system will now be described with the sample holder 58 at its Figure 1, Figure 4 position as a starting point. A reference reading is continually made in the optical system with light passing through reference ~'~ aperture ~ , carriage motor 40 being energized and always at or seeking a balance position. A blood sample is inserted in station 68 and sample drive motor 50 actuated as by a manual switch. Momentary switch actuation starts the rotation of the sample holder 58. The consequent unseating and opening of the detent switch 74 de-energizes carriage motor 40 until the hold-er reaches its test position in which test aperture 72 is aligned at the optical axis 14 and the detent switch again s~ats to energize the carriage motor 40 and stops sample motor 50. While the blood sample is thus in the optical axis, light transmitting through it to the photo detectors 20 and 24 sig-nals the carriage motor 40 to position the filter wedge 32 in -~:~3~

response to any imbalance in photo detector signals until a null condition is reached. At this point the desired reading is made. The manual switch again starts motor 50, this time in the reverse direction, and again detent switch 74 unseats and opens to de-energize the carriage motor 40 until the ini-tial position is reached with reference aperture 66 once again in the optical axis and the sample holder accessible for removal of the sample. A~ this po:int, motor 50 stops when cam 60 actuates limit switch 62.
The foregoing speciication describes the concept of this invention and the best mode presently contemplated for practicing the same. The scope of the invention is limited only by the purview of the ollowing claims.

Claims (5)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A system for measuring the concentration of bilirubin in a test sample of blood serum, including:
a light source to direct light along an optical axis to illuminate a test station, a sample handling system for presentation of test samples of blood serum at said test station, said sample holding system including, a sample holder adapted to hold a blood sample placed thereon and movable relative to said optical axis in a defined locus between a reference position in which the sample is out of the optical axis, and a test position in which the sample is on the optical axis at said test station, and said sample holder forming a reference aperture and a test aperture which are sequentially positioned at said test station when said sample holder is at its reference and test positions respectively, an objective lens to project light further along said optical axis from said test station, a beam divider disposed on said optical axis to receive light from said objective lens and to partially reflect and partially transmit same along parallel optical paths, a band pass filter in each of said parallel optical paths to transmit substantially only light of one wavelength, a photodetector behind said band pass filter in each of said parallel optical paths to receive light transmitted thereby, an adjustable light attenuator in one of said parallel optical paths for adjustable varying the intensity of light transmitted therethrough to the associated photodetector, said photodetectors electrically connected to a carriage motor which is responsive to any imbalance in the signals from said photodetectors to move said light attenuator to a position at which the photodetector signals to said motor are in balance, the resulting position of said light attenuator being correlated to bilirubin concentration in said test sample.
2. A system as defined in Claim 1 in which said light attenuator is a gradient density filter.
3. A system as defined in Claim 2 in which said gradient density filter forms an optical wedge.
4. A system as defined in Claim 1 further including means responsive to the position of said sample holder to energize a carriage motor when said sample holder is in its reference and test positions and to deenergize said carriage motor at all other positions of said sample holder.
5. A system as defined in Claim 1, further including a sample drive motor operatively connected to said sample holder to move the same from said reference position to said test position and from said test position to said reference position, and switch means to start and stop said sample drive motor at said reference and test positions.
CA000350046A 1979-05-14 1980-04-17 Apparatus for measurement of blood bilirubin concentration Expired CA1139124A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US3908379A 1979-05-14 1979-05-14
US06/039,083 1979-05-14

Publications (1)

Publication Number Publication Date
CA1139124A true CA1139124A (en) 1983-01-11

Family

ID=21903574

Family Applications (1)

Application Number Title Priority Date Filing Date
CA000350046A Expired CA1139124A (en) 1979-05-14 1980-04-17 Apparatus for measurement of blood bilirubin concentration

Country Status (7)

Country Link
JP (1) JPS55152443A (en)
AT (1) AT370524B (en)
CA (1) CA1139124A (en)
DE (1) DE3018343A1 (en)
FR (1) FR2456948A1 (en)
GB (1) GB2046901B (en)
HK (1) HK18985A (en)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS57138379A (en) * 1981-02-16 1982-08-26 Aroozu:Kk Enzymic reaction and measuring apparatus of bilirubin
JPS59214768A (en) * 1983-05-21 1984-12-04 Mochida Pharmaceut Co Ltd Blood inspector
DE19609410C2 (en) * 1996-03-04 2002-04-25 Biotronik Mess & Therapieg Device for determining blood oxygen saturation
US9448134B2 (en) 2014-06-23 2016-09-20 Exxonmobil Upstream Research Company Systems for detecting a chemical species and use thereof
WO2015199912A1 (en) 2014-06-23 2015-12-30 Exxonmobil Upstream Research Company Image quality enhancement of a differential image for a multiple detector system
US9442011B2 (en) 2014-06-23 2016-09-13 Exxonmobil Upstream Research Company Methods for calibrating a multiple detector system
WO2015199911A1 (en) 2014-06-23 2015-12-30 Exxonmobil Upstream Research Company Methods and systems for detecting a chemical species

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR894581A (en) * 1942-05-13 1944-12-28 Joens & Co W H Electric light changing colorimeter with automatic equalization
US3306156A (en) * 1957-02-19 1967-02-28 Du Pont Method and apparatus for photometric analysis
FR1410780A (en) * 1964-10-07 1965-09-10 Gretag Ag Photoelectric measuring device
US3569721A (en) * 1969-01-13 1971-03-09 American Optical Corp Measuring bilirubin in blood using light at two wavelengths

Also Published As

Publication number Publication date
GB2046901B (en) 1983-06-15
FR2456948B1 (en) 1984-11-23
AT370524B (en) 1983-04-11
GB2046901A (en) 1980-11-19
DE3018343A1 (en) 1980-11-27
HK18985A (en) 1985-03-22
ATA250680A (en) 1982-08-15
FR2456948A1 (en) 1980-12-12
JPS55152443A (en) 1980-11-27

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