Apparatus for monitoring chemical reactions

• US 4,430,299 A
• Filed: 06/18/1981
• Issued: 02/07/1984
• Est. Priority Date: 06/18/1981
• Status: Expired due to Fees

• Current Assignee: Coulter Electronics, Inc.
• Original Assignee: Coulter Electronics, Inc.
• Inventors: Horne, Thomas
• Primary Examiner(s): Marcus, Michael S.
• Application Number:
  US06/275,104
• Time in Patent Office: 964 Days
• Field of Search: 422/64, 422/67, 422/63, 422/65, 422/66, 356/435, 356/246, 364/497, 364/498
• US Class Current: 422/64
• CPC Class Codes: G01N 2035/00138 Slides
• CPC Class Codes: G01N 2035/00346 Heating or cooling arrangements
• CPC Class Codes: G01N 2035/00752 bar codes
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 35/00029 provided with flat sample substrates, e.g. slides G01N35/028 takes precedence
• CPC Class Codes: Y10T 436/113332 with conveyance of sample along a test line in a container or rack
• CPC Class Codes: Y10T 436/114165 with step of insertion or removal from test line

Abstract

Apparatus for monitoring chemical reactions occurring on a slide, cartridge or other reflective carrier in which the nature of the reaction is determined quantitatively by means of a change in color. The reaction products are illuminated by radiant energy of a known wavelength and the reaction is detected and/or monitored by the reflection of the radiant energy from the sample where the reaction is occurring. A plurality of samples carried on such slides is disposed in alignment in a circle or a line and a rotor or carriage carrying plural photometers or a single photometer producing plural beams at different wavelengths is moved relative to the samples, the beams being directed at the samples. Each sample is scanned at least once as the carriage moves or the rotor rotates and the reflected radiant energy is captured by photo-responsive devices and channeled to a computer where the data is processed and information acquired concerning the respective samples with regard to end points and kinetic characteristics of their reactions.

Claims

1. Apparatus for monitoring chemical reactions occurring or having occurred in a plurality of sample substances carried respectively by a plurality of cartridges of generally strip-like planar construction, the reaction occurring or having occurred in any cartridge being detected by directing a beam of radiant energy to illuminate a cartridge at a radiant energy receiving surface thereof which provides access to said substance carried by the cartridge and measuring the modified radiation reflected from the sample substance carried by said cartridge and the radiant energy receiving surface, said apparatus comprising:

A. a stationary support structure,

B. a plurality of cartridges of generally strip-like planar construction,

C. means on said structure for fixedly supporting a plurality of said cartridges in a geometric line array and each cartridge having a sample substance carried thereby and a radiant energy receiving surface providing access for radiant energy to said sample substance, the radiant energy receiving surfaces of all said cartridges facing to the same side of said array, said cartridges being supported by said supporting means in such a manner as to enable the removal and replacement of any one independently of all others,

D. a movable carrier on said support structure and means mounting said movable carrier for guided movement substantially parallel to said geometric line,

E. at least one photometer carried on said movable carrier, said photometer having a source of radiant energy and means forming a beam of said radiant energy and directing said beam to said cartridges, the formed beam being disposed to impinge against said cartridges at the radiant energy receiving surfaces thereof as the movable carrier moves relative to said array,

F. the angle of impingement of said beam with said radiant energy receiving surfaces relative to the planes of said surfaces being such as to enable detection of reflected radiant energy,

G. said photometer including photoresponsive means on the same side of said surface as said beam arranged to receive modified radiation reflected from said cartridges directly from said surfaces, the spatial relationship of the beam forming means and photoresponsive means being fixed,

H. means for moving the movable carrier on a program of movement to direct said beam at the cartridges selectively if not sequentially, the cartridge support being such that said removal of any one of said cartridges from said support being accomplished without interruption of said program of movement of said movable carrier,

I. the photoresponsive means being responsive to the modified reflected radiation to produce an electrical signal related to the chemical condition of the sample substance, if any, carried by the cartridge which the directed beam illuminates, movement of the movable carrier serving to produce a plurality of said signals from the sample substances of those cartridges which have been illuminated,

J. means for generating usable data from said signals and

K. means for coupling the signals from the carrier to said last-mentioned means.

2. The apparatus as claimed in claim 1 in which the movable carrier is a carriage, the geometric line is rectilinear and the mounting means comprise cooperating track and trackriding means on the carriage and support structure.

3. The apparatus as claimed in claim 1 in which there is a plurality of photometers mounted on the movable carrier and said photoresponsive means include plural devices for receiving radiation from the respective beam forming means of said photometers.

4. The apparatus as claimed in claim 1 in which the movable carrier has circuitry mounted thereon for converting analog signals produced by said photoresponsive means to digital signals and the coupling means transmit only signals from said photoresponsive means which are digital.

5. The apparatus as claimed in claim 1 in which the said coupling means comprise slide and slider means mounted on said movable carrier and said support structure.

6. The apparatus as claimed in claim 1 in which the means for moving the movable carrier comprise a stepping motor and the program of movement comprises stepping the movable carrier from cartridge to cartridge, dwelling at any cartridge and moving to another cartridge.

7. The apparatus as claimed in claim 1 in which means are provided for dissecting the beam directed to said cartridges into multiple wavelength components whereby to illuminate each of said cartridges with different wavelengths of energy, the photoresponsive means being arranged to respond to said different wavelengths of energy.

8. The apparatus as claimed in claim 10 in which said dissecting means comprise a filter wheel carrying different filters and means on said movable carrier for rotating the filter wheel and bringing the different filters sequentially into the path of the directed beam.

9. The apparatus as claimed in claim 1 in which the movable carrier is a rotor mounted on an axis and the geometric line is a circle coaxial with said rotor.

10. The apparatus as claimed in claim 9 in which the said coupling means comprise a slip ring device having a rotary part and a fixed part, the rotary part having electrical connections from the rotor connected thereto and being secured to the rotor, the fixed part being mounted to said support structure and having connections to the usable data generating means connected thereto.

11. The apparatus as claimed in claim 9 in which the means for supporting the cartridges are arranged to tilt all of the cartridges when in position on an approximately 45°

angle with the horizontal, facing the energy receiving surface of each cartridge inwardly toward said axis and downwardly, the directed beam of radiant energy being horizontal, the photoresponsive means having its active element facing upward and arranged to receive the reflected energy from said cartridges as said energy passes downward.

12. The apparatus as claimed in claim 9 in which there is a plurality of photometers on the movable carrier, said photometers being radially disposed on said rotor with each photometer forming a separate beam of radiant energy, the cartridges adapted to be facing inwardly and tilted downwardly when disposed on said supporting means, there being at least a separate photoresponsive device for each photometer arranged with a sensitive element facing upward to receive the reflected radiation from said cartridges.

13. The apparatus as claimed in claim 9 in which the means for fixedly supporting said plurality of cartridges are arranged to hold said cartridges in said circle in a disposition with the surfaces of said cartridges carrying said sample substances all facing said beam and being tilted relative to said beam whereby the beam will engage said substances and subtend an acute and an obtuse angle therewith, the modified radiant energy being reflected to the obtuse angle side of each cartridge and substantially diverted from returning along said beam, said photoresponsive means being located to receive said reflected and modified radiant energy.

14. The apparatus as claimed in claim 1 in which the means for fixedly supporting said plurality of cartridges are arranged to hold said cartridges in a disposition with the sample substances carried thereby facing said beam and with the angle between said beam and each of the radiant energy receiving surfaces when engaged by said beam being other than 90°

whereby the modified radiant energy reflected from said surfaces is substantially diverted from returning along said beam, said photoresponsive means being located to receive said reflected and modified radiant energy.

15. Apparatus for monitoring chemical reactions occurring or having occurred in a plurality of sample substances carried respectively by a plurality of cartridges of generally strip-like planar construction, the reaction occurring or having occurred in any cartridge being detected by directing a beam of radiant energy to illuminate a cartridge at a radiant energy receiving surface thereof which provides access to said substance carried by the cartridge and measuring the modified radiation reflected from the sample substance carried by said cartridge and the radiant energy receiving surface, said apparatus comprising:

A. a support structure including a housing having a cover member, said cover member having a plurality of slots defining a geometric line,

B. a plurality of cartridges of generally strip-like planar construction,

C. means on said structure for fixedly supporting a plurality of said cartridges in an array along said geometric line and each cartridge having a sample substance carried thereby and a radiant energy receiving surface providing access for radiant energy to said sample substance, the radiant energy receiving surfaces of all said cartridges facing to the same side of said array, the said cartridge supporting means comprising receptacles below the cover member, each slot comprising the entrance to a receptacle,

D. a movable carrier on said support structure and means mounting said movable carrier for guided movement substantially parallel to said geometric line,

E. at least one photometer carried on said movable carrier, said photometer having a source of radiant energy and means forming a beam of said radiant energy and directing said beam to said cartridges, the formed beam being disposed to impinge against said cartridges at the radiant energy receiving surfaces thereof as the movable carrier moves relative to said array,

F. the angle of impingement of said beam with said radiant energy receiving surfaces relative to the planes of said surfaces being such as to enable detection of reflected radiant energy,

G. said photometer including photoresponsive means on the same side of said surface as said beam arranged to receive modified radiation reflected from said cartridges directly from said surfaces, the spatial relationship of the beam forming means and photoresponsive means being fixed,

H. means for moving the movable carrier on a program of movement to direct said beam at the cartridges selectively if not sequentially,

I. the photoresponsive means being responsive to the modified reflected radiation to produce an electrical signal related to the chemical condition of the sample substance, if any, carried by the cartridge which the directed beam illuminates, movement of the movable carrier serving to produce a plurality of said signals from the sample substances of those cartridges which have been illuminated,

J. means for generating usable data from said signals and

K. means for coupling the signals from the carrier to said last-mentioned means.

16. The apparatus as claimed in claim 15 in which each receptacle has a mask blocking the cartridge which may be disposed in said receptacle from the said source of radiant energy but for a slit to admit the beam, any reflected radiation from the cartridge being capable of passing back through said slit but on an alignment different from that of the directed beam, the photoresponsive means being located to receive the reflected radiation exclusive of any radiation from the directed beam.

17. The apparatus as claimed in claim 15 in which an identifying signal device is disposed on said cover alongside and identifying each slot and in which means are provided to operate said identifying signal device when the electrical signal from the sample substance of a cartridge in said slot has a predetermined character.

18. The apparatus as claimed in claim 15 in which partition means are provided separating the receptacles at least optically from one another.

19. The apparatus as claimed in claim 15 in which an identifying signal producing device is provided individual to each receptacle and said identifying signal producing device includes means for operating the identifying signal producing device of any receptacle when the electrical signal from the sample substance of the cartridge in said last mentioned receptacle has a predetermined character.

20. The apparatus as claimed in claim 15 in which each receptacle has a stop member to limit and define the extent to which a cartridge can be introduced into said receptacle.

21. The apparatus as claimed in claim 20 in which each receptacle includes spring means for holding the cartridge frictionally engaged therein.

22. Apparatus for monitoring chemical reactions occurring or having occurred in a plurality of sample substances carried respectively by a plurality of cartridges of generally strip-like planar construction, the reaction occurring or having occurred in any cartridge detected by directing a beam of radiant energy to illuminate a cartridge at a radiant energy receiving surface thereof which provides access to said substance carried by the cartridge and measuring the modified radiation reflected from the sample substance carried by said cartridge and the radiant energy receiving surface, said apparatus comprising:

A. a support structure including an enclosed housing,

B. a plurality of cartridges of generally strip-like planar construction,

C. said structure having means within said housing for accommodating and fixedly mounting a plurality of said cartridges in said housing in a circular array and each cartridge having a sample substance carried thereby and a radiant energy receiving surface providing access for radiant energy to said sample substance from the interior of said housing, the radiant energy receiving surfaces of all said cartridges facing radially inward, the housing having passageway means therein enabling insertion of said cartridges from the exterior of said housing into respective ones of said accommodating and mounting means, said passageway means and the accommodating and mounting means being geometrically related substantially to restrict external radiant energy from entering the interior of said housing,

D. a rotary carrier on said support structure and means mounting said carrier coaxially with said array,

E. at least one photometer mounted on said carrier and having a source of radiant energy and means forming a beam of said radiant energy and directing said beam to said cartridges, said formed beam being disposed to impinge against said cartridges at the respective radiant energy receiving surfaces thereof as the carrier rotates relative to said array,

F. the angle of impingement of said beam with said radiant energy receiving surfaces relative to the planes of said surfaces being such as to enable detection of reflected radiant energy,

G. said photometer including photoresponive means on the same side of said surface as said beam arranged to receive modified radiation reflected from said cartridges directly from said surfaces, the spatial relationship of the beam forming means and photoresponsive means being fixed,

H. means for rotating said carrier any desired numbers of revolutions to direct said beam at the cartridges in sequence around said array,

I. the photoresponsive means being responsive to the modified reflected radiation to produce an electrical signal related to the chemical condition of the sample substance, if any, carried by the cartridge which the directed beam illuminates, rotation of said carrier serving to produce a plurality of said signals from the sample substances of those cartridges which have been illuminated,

J. said cartridge mounting means, housing and passageway means being constructed and arranged in such a manner as to enable the removal of and replacement of any one or more cartridge independently of all others and without interrupting the rotation of the carrier,

K. means for generating usable data from said signal and

L. means for coupling the signals from the carrier to said last-mentioned means.

23. Apparatus for monitoring chemical reactions occurring or having occurred in a plurality of sample substances carried respectively by a plurality of cartridges of generally strip-like planar construction, the reaction occurring or having occurred in any cartridge being detected by directing a beam of radiant energy to illuminate a cartridge at a radiant energy receiving surface thereof which provides access to said substance carried by the cartridge and measuring the modified radiation reflected from the sample substance carried by said cartridge and the radiant energy receiving surface, said apparatus comprising:

A. a support structure,

B. a plurality of cartridges of generally strip-like planar construction,

C. means on said structure for fixedly supporting a plurality of said cartridges in a circular array and each cartridge having a sample substance carried thereby and a radiant energy receiving surface providing access for radiant energy to said sample substance, the radiant energy receiving surfaces of all said cartridges facing to the same side of said array, said cartridges being supported by said supporting means in such a manner as to enable the removal and replacement of any one independently of all others,

D. a rotor on said support structure and means mounting said rotor for guided rotational movement on an axis coaxially of said array,

E. at least one photometer carried on said rotor, said photometer having a source of radiant energy and means forming a beam of said radiant energy and directing said beam to said cartridges, the formed beam being disposed to impinge against said cartridges at the radiant energy receiving surfaces thereof as the rotor moves relative to said circular array,

F. the angle of impingement of said beam with said radiant energy receiving surfaces relative to the planes of said surfaces being such as to enable detection of reflected radiant energy,

G. said photometer including photoresponsive means arranged to receive modified radiation reflected from said cartridges, the spatial relationship of the beam forming means and photoresponsive means being fixed,

H. means for rotating the rotor on a program of movement to direct said beam at the cartridges selectively if not sequentially

I. the photoresponsive means being responsive to the modified reflected radiation to produce an electrical signal related to the chemical condition of the sample substance, if any, carried by the cartridge which the directed beam illuminates, rotational movement of the rotor serving to produce a plurality of said signals from the sample substance of those cartridges which have been illuminated,

J. said means for supporting the cartridge being arranged to tilt all of the cartridges when in position on an approximately 45°

angle with the horizontal, facing the energy receiving surface of each cartridge inwardly toward said axis and downwardly, the directed beam of radiant energy being horizontal, the photoresponsive means having sensitive element means facing upward and arranged to receive the reflected energy from said cartridges as said energy passes downward,

K. means for generating usable data from said signals and

L. means for coupling the signals from the rotor to said last-mentioned means.

24. Apparatus for monitoring chemical reactions occurring or having occurred in a plurality of sample substances carried respectively by a plurality of cartridges of generally strip-like planar construction, the reaction occurring or having occurred in any cartridge being detected by directing a beam of radiant energy to illuminate a cartridge at a radiant energy receiving surface thereof which provides access to said substance carried by the cartridge and measuring the modified radiation reflected from the sample substance carried by said cartridge and the radiant energy receiving surface, said apparatus comprising:

A. a support structure,

B. a plurality of cartridges of generally strip-like planar construction,

C. means on said structure for fixedly supporting a plurality of said cartridges in a circular array and each cartridge having a sample substance carried thereby and a radiant energy receiving surface providing access for radiant energy to said sample substance, the radiant energy receiving surfaces of all said cartridges facing to the same side of said array, said cartridges being supported by said supporting means in such a manner as to enable the removal and replacement of any one independently of all others,

D. a rotor on said support structure and means mounting said rotor for guided rotational movement on an axis coaxially of said array,

E. a plurality of photometers carried on said rotor, said photometers being radially disposed on said rotor, said photometers having source means of radiant energy and each photometer having means forming a separate beam of said radiant energy and directing said beam to said cartridges, the formed beam being disposed to impinge against said cartridges at the radiant energy receiving surfaces thereof as the rotor moves relative to said circular array,

F. the angle of impingement of said beam with said radiant energy receiving surfaces relative to the planes of said surfaces being such as to enable detection of reflected radiant energy,

G. said photometers including photoresponsive means arranged to receive modified radiation reflected from said cartridges, the spatial relationship of the beam forming means and photoresponsive means being fixed,

H. means for rotating the rotor on a program of movement to direct said beams at the cartridges selectively if not sequentially,

I. the photoresponsive means being responsive to the modified reflected radiation to produce an electrical signal related to the chemical condition of the sample substance, if any, carried by the cartridge which the directed beam illuminates, rotational movement of the rotor serving to produce a plurality of said signals from the sample substances of those cartridges which have been illuminated,

J. the cartridges adapted to be facing inwardly and tilted downwardly when disposed on said supporting means, said photoresponsive means comprising at least a separate photoresponsive device for each photometer arranged with a sensitive element facing upward to receive the reflected radiation from the cartridges,

K. means for generating usable data from said signals and

L. means for coupling the signals from the carrier to said last-mentioned means.