WO1997007391A1

WO1997007391A1 - Serum index sample probe

Info

Publication number: WO1997007391A1
Application number: PCT/US1996/013139
Authority: WO
Inventors: Jack Mc Neal
Original assignee: Beckman Instruments, Inc.
Priority date: 1995-08-18
Filing date: 1996-08-12
Publication date: 1997-02-27

Abstract

A serum index sample probe having a cuvette (17) with a cylindrical channel (39) coupled between a hollow cylindrical member (25) and a hollow cylindrical needle (23) by an optics block (13). The channel and the needle have matching diameters and are coaxially aligned along an axis (41), defining a smooth bore therebetween to reduce dead volumes. The cuvette is positioned proximate to a puncturing tip of the needle which, along with the smooth bore, reduces turbulence and bubbles in the flow path. The optics block (13) provides a plurality of optical paths to the cuvette while maintaining a linear flow path. The optics block is a manifold having a central aperture (15), a perimeter surface (61) disposed concentrically about the central aperture, and a plurality of bore holes (55, 57, 59).

Description

Serum Index Sample Probe

Technical Field

The present invention pertains to the field of sample probes for optical absorbance and scattering measurements. More particularly, the present invention pertains to a sample probe particularly suited for optical testing of a flow of a sample, for example blood, by measuring the optical characteristics of the sample under influence of an external light source.

Background Art The measurement of the optical characteristics of a fluid is typically used to determine the fluid's absorbance, turbidimetric and nephelometric properties, as well as the number of particles present and the particles' properties. Absorbance, turbidimetric and nephelometric measurements are made at different angles with respect to the incident light. The measurements have proved advantageous to the medical profession by allowing clinical analysis of patient samples. As the drive to reduce health care costs continues, automating the analysis of patient samples becomes increasingly important. One aspect of automation is assessing the suitability of a particular sample for analysis. Clinical laboratory practice has traditionally been to visually inspect the patient sample for conditions that could compromise the sample's suitability for analysis. These conditions may include Hemolysis (ruptured red blood cells) , Icteris (excessive Bilirubin) and Lipemia (high, visible lipid content) . Measuring the optical characteristics of a sample abrogates the need for visual inspection. A conventional technique for determining the optical characteristics of a fluid sample includes placing the sample in a separate receptacle, test tube or cuvette and positioning the container in the flow path of a beam of light or other radiant energy.

U.S. Pat. No. 5,241,368 discloses a fiber-optic probe for absorbance and turbidity measurements of samples contained in separate receptacles. The probe includes an elongated probe assembly removably insertable into a fluid, and a photometric light source to transmit light through fiber-optic cables. One end of the assembly includes a bore through which fluid may pass, with the fiber-optic cables terminating on one side of the bore. Disposed opposite to the fiber-optic cables in the bore is a mirrored surface. Light reflected from the mirrored surface is directed to a light detector to measure the light output of the probe assembly. In this manner, light twice passes through the fluid flowing through the bore, producing an indication of the absorbance or turbidity of the fluid. The drawbacks with this device is that throughput is reduced by having to separate the samples into different containers and then inserting the probe into the different samples.

Other techniques have been employed to overcome the deficiencies of using separate receptacles to contain samples. Some prior art systems forego visual inspection by an operator altogether and place a sample into an analyzer without determining the suitability of the sample for analysis. This technique results in wasted analysis time.

U.S. Pat. No. 4,440,497 discloses a combination absorbance fluorescence aspirating thermal cuvette including a flow cell having axial and radial optical paths. A source of light directs a beam along the axis of a flow cell with a detector positioned opposite to the source of light to detect light exiting the flow cell. A detector is also positioned radially from the axis of the flow cell to detect light exiting in that direction. In this manner, a plurality of in-situ measurements may be made simultaneously while a flow of fluid passes through the cell.

More recent devices have been designed using fiber-optic waveguides in attempts to overcome the deficiencies of earlier techniques. U.S. Pat. No. 5,181,082 to Jeannotte et al. discloses an on-line titration apparatus using colorimetric end point detection. This apparatus includes a sample chamber to contain a test fluid that is transparent and disposed between two conical reflecting surfaces. Light guides are optically connected to the conical reflecting surfaces to direct light parallel to the axis of the sample chamber. Light traveling along an incident waveguide to a reflecting surface is reflected so as to propagate through the fluid perpendicular to the fluid flow. Light exiting the fluid is incident on a reflecting surface so as to be transmitted through a return waveguide parallel to the sample chamber. The drawbacks of the two aforementioned devices is that the flow path defined by each device includes dead volumes which increases the possibility of carry-over between samples, which can greatly affect measurement, particularly if high concentration samples are carried over into low concentration samples. The dead volumes can also cause turbulence and bubbles in the sample flow, further obscuring measurements. To reduce the carry-over problem, great amounts of wash fluid is necessitated to remove the carry-over/ residue in the flow cell. This results in an increased amount of waste fluid. For large scale analysis operations, the increased amount of fluid poses several problems including increased costs, reduced throughput, as well as running afoul of federal environmental protection regulations.

The object, therefore, of the present invention is to provide an improved sample probe having reduced dead volume to increase throughput and abrogate turbulence in the sample flow.

It is a further object of the invention to measure the optical characteristics of a sample for analysis as the sample is transferred from a container to determine the suitability of the sample for analysis.

Summary of the Invention

These objects have been achieved with a sample probe including a cuvette having a cylindrical channel coupled between a hollow cylindrical member and a hollow cylindrical needle by an optics block, with the channel and the needle having matching internal diameters and coaxially aligned along an axis, defining a smooth bore therebetween to virtually eliminate dead volumes. The cuvette is positioned proximate to a puncturing tip. The proximity of the cuvette with the puncturing tip of the needle, along with the smooth bore, reduces turbulence and bubbles in the flow path. The optics block provides a plurality of optical paths to the cuvette. The optics block is an opaque multiported manifold having a central aperture, a perimeter surface disposed concentrically about the central aperture, and a plurality of bore holes. The bore holes may include lenses and filters as required by the optical design of the system. The cuvette is received within the central aperture. The plurality of bore holes extend from the central aperture, perpendicular to the sample flow, terminating in an opening proximate to the perimeter surface. In this manner, absorbance, turbidimetric and nephelometric measurements may be simultaneously performed in-situ as a sample is contained statically within, or flows through, the probe.

Brief Description of the Drawings Fig. 1 is an exploded perspective view of the serum index sample probe in accord with the present invention.

Fig. 2 is a side cross-sectional view of the serum index sample probe in accord with the present invention.

Fig. 3 is a cross-sectional side view of a cuvette as shown in Fig. 2.

Fig. 4 is a top cross-sectional view of an optics block shown in Figs. 1 and 2 above. Fig. 5 is a simplified plan view of the serum index sample probe configured for operation, in accord with the present invention.

Best Mode for Carrying Out the Invention Fig. 1 shows an exploded view of the sample probe 11 including a manifold, such as optics block 13, having a central aperture 15 to receive a cuvette 17, as well as a plurality of clearance holes 19 to receive screws 21 or other fastening means therethrough. A hollow needle 23, attached to a first bell member 27, and a tubular member 25, attached to a second bell member 29, are disposed on opposite ends of the cuvette 17. Disposed proximate to each of the first 27 and second 29 bell members, on the side opposite to the cuvette 17, is a bearing surface 31 and 33, respectively. Each bearing surface 31 and 33 includes a plurality of clearance holes 35 and 37, respectively, as well as a central through hole 34 and 36, respectively. The clearance holes 35 and 37 of the bearing surfaces 31 and 33 are positioned so as to be axially aligned with each of the clearance holes 19 on the optics block 13, once in a final seating position. Typically, the first 27 and second 29 bell members and the bearing surfaces 31 and 33 are formed from a metal. Referring also to Fig. 2, the sample probe is shown upon final assembly. Upon reaching a final seating position with respect to the optics block 13, each end 43 and 45 of the cuvette 17 is contained within the central aperture 15, so that the optics block 13 completely en¬ capsulates the cuvette 17. Typically, the cuvette 17 is cylindrical and includes a cylindrical channel 39 which defines a flow axis 41. The first 27 and second 29 bell members each includes cup portion 47 and 49, respectively. Cup portion 47 receives end 43 and cup portion 49 receives end 45. Bearing surfaces 31 and 33 are positioned adjacent to a cup portions 47 and 49, respectively, with a portion of each bell member fitting in the central through hole. Fastening means, such as screws 21, are attached so that each screw passes through a clearance hole 35 in the first bearing surface 31, a clearance hole 19 in the optics block 13, and a clearance hole 37 in the second bearing surface 33. A nut 51 may be placed over the end of each screw 21 to securely tighten the assembly. Upon tightening the nut, the bearing surfaces move towards each other, compressing the bell members, forming a fluid-tight seal between the cuvette 17, the needle 23 and the tubular member 25. To facilitate a fluid-tight seal, a resilient washer 28 made of a suitable material, e.g., Teflon, may be disposed between the cuvette and the cup portion of each resilient member, as shown in Fig. 1. Although the compression of the resilient members has been described in accordance with a nut and bolt arrangement, any fastening means may be employed. For example, the clearance holes in one or both of the bearing surfaces may be threaded, thereby obviating the need for a nut. Critical to practicing the invention is the axial alignment of the tubular member 25, the needle 23 and the channel 39 so as to form a smooth bore, as shown in Fig. 3. To that end, it is necessary that the tubular member 25 and the needle 23 have the same cross-sectional shape as the channel 19. In the present invention, the tubular member 25 and the needle 23 would be cylindrical, having the same internal diameter as the channel 19, thereby forming a smooth bore with a constant diameter along its length. If resilient washer 28 were employed, the washer 28 would have an aperture having a diameter equivalent to the internal diameter of channel 19, and coaxially aligned therewith. The smooth bore also reduces dead volumes in the flow path, greatly reducing carry-over and thereby the amount of fluid required to clean the probe. In high volume testing applications, the reduced waste fluid can result in reduced processing costs, as well as increased ability to comply with ever increasing environmental regulations. This design also greatly reduces the turbulence of a fluid flow through the probe, which reduces the amount of bubbles created in the flow. Reducing the bubbles in the flow greatly increases the sensitivity of the probe, because bubbles can obscure optical measurements.

To obtain the smooth bore, it is preferred that the outer diameter of the cuvette 19, as defined by the outer surface 51, and inner diameter, defined by the channel 39, be concentrically disposed about the flow axis 41. The cup portion of each bell member defines a cup diameter 53 coextensive with the outer diameter. The cup diameter of the first bell member 47 and the diameter of the tubular member 25 are concentrically disposed with each other, and the cup diameter of the second bell member 49 and the diameter of the needle 23 are concentrically disposed with each other. This structure allows the cups portions to align the channel with the tubular member and the needle so that the flow path formed therebetween is a smooth bore. In addition to the smooth bore, the cuvette is placed proximate to a puncturing tip 30 of the needle 23 which also reduces the length of the flow path, thereby further reducing the time and distance over which bubbles could form. This design also increases throughput as it allows transferring a sample via the probe simultaneous with performing absorbance, turbidimetric and nephelometric analysis of the sample. It is preferred that the cuvette is placed as close as possible to the puncturing tip, consistent with the need to extend to a bottom of a sample container.

Fig. 4 shows the optics block 13 including a plurality of bore holes 55, 57 and 59 extending from the central aperture 15 of the optics block 13, perpendicular to the flow axis 41. Each of the bore holes 55, 57 and 59 terminates in an opening proximate to the perimeter surface 61 of the optics block 13. Fittings 55a, 57a and 59a may extend from each opening, respectively. Fittings 55a, 57a and 59a may be any type of fitting capable of coupling to a fiber-optic cable. The optics block 13 may be formed of any rigid opaque material that can be manufactured to accommodate fittings 55a, 57a and 59a. Although three bore holes are shown, any number of bore holes may be present, dependent upon the application. In addition, the perimeter surface may include a plurality of flat sections 61a - 61h, equally spaced about the perimeter surface, defining an octagon. Although eight flat sections are shown, any number may be present, defining, e.g., a hexagon, a cube, etc. An advantage of providing the plurality of flat sections is the ease of positioning the bores at selected angles with respect to each other, as well as aligning the bores to provide a perpendicular optical path with respect to the channel. Referring also to Fig. 5, in operation, an aspirating means, such as a motorized syringe 63, is connected to the tubular member 25. A sample flow will be present in the channel of the cuvette 17 by aspirating a sample through the puncturing tip 30 of the needle 23. Typically, a fiber optic cable 55b, 57b, 59b will be connected to each fitting 55a, 57a and 59a. At least one of the fiber optic cables will be optically coupled to a source of light 69, e.g., white light. A further extension of the probe would be to have a series of light-emitting diodes (LEDs) in optical communication with the optics block by fiber-optic cable. The LEDs could be activated in sequence to test the spectral characteristics of the sample at differing wavelengths. The spectral characteristics of the sample could be tested using LEDs emitting any wavelength of light desired, depending upon the application. The remaining fiber optic cables will be optically coupled to various photodetectors 65 and 67. In this fashion, the bores define a plurality of optical paths to the sample flow in the channel of the cuvette. For example, light may be transmitted through bore 55. Light passing directly through the sample flow in the channel is collected by bore 59 and transmitted through the fiber-optic cable 59b to a photodetector 67 which may be used to perform a turbidimetric analysis of the sample flow. Light scattered through the sample flow may be collected by bore 57 and transmitted via a fiber-optic cable 57b to a second detector 65 which may be used to perform nephelometric analysis of the sample flow. It is evident that the optics block 13 allows simultaneously collecting light from a plurality of fixed angles, with respect to the incident light transmitted through bore 55.

The key advantage of this invention is that it is relatively inexpensive to manufacture, yet provides increased sensitivity to optical measurements by reducing carry-over and turbulence in a flow path. It also increases the throughput of a sample handling by permitting simultaneous absorbance, turbidimetric and nephelometric analysis of a sample, while the sample is being transferred between work stations.

Claims

1. A probe for receiving a sample flow to be tested under the influence of an external light source, comprising: a transparent body having first and second openings at opposed ends, and a channel extending therebetween, a first hollow member having a fluid inlet, adapted to receive a sample therethrough, and a fluid outlet, positioned adjacent to said second opening of said body; a second hollow member having an inlet port positioned adjacent to said first opening of said body, with said first hollow member, said second hollow member and said channel defining a linear flow path; and means, positioned about said transparent body, for providing a plurality of optical paths perpendicular to said channel.

2. The probe as recited in claim 1 wherein said channel and said first hollow member define a cylindrical flow path having a constant diameter over the entire length of said flow path.

3. The probe as recited in claim 1 wherein said providing means is a manifold having a central aperture, a perimeter surface disposed concentrically about said central aperture and a plurality of bore holes, with a normal to said perimeter surface being perpendicular to said flow path and said plurality of bore holes extending from said central aperture, terminating in an opening proximate to said perimeter surface, said transparent body being received within said central aperture with said bore holes defining a plurality of optical paths to said channel.

4. The probe as recited in claim 1 wherein said transparent body is a cuvette.

5. The probe as recited in claim 1 wherein said first tubular member is a hollow needle with said inlet defining an impaling portion.

6. The probe as recited in claim 1 wherein said second tubular member is cylindrical, with said channel, said first tubular member and said second tubular member having matching diameters and coaxially aligned along an axis parallel to said flow path.

7. The probe as recited in claim 1 wherein said transparent body is a cylindrical cuvette having an outer surface defining an outer diameter, with said diameter of said channel and said outer diameter concentrically disposed about said axis.

8. A flow cell for receiving a sample flow to be tested under the influence of an external light source, comprising: a first tubular member having an inlet adapted to receive a sample therein and a second end positioned opposite to said inlet; a second tubular member having distal and proximal ends; a transparent body disposed between said first and second tubular members, said transparent body including a channel extending completely therethrough and in flow communication with both said second end and said proximal end, with said channel and said first tubular member defining a cylindrical flow path having a constant diameter; a manifold disposed about said transparent body including a plurality of bore holes allowing transmission of light from said source and detection of light passing through said sample flow along an optical axis perpendicular to said flow path.

9. The flow cell as recited in claim 8 wherein said transparent body is a cuvette.

10. The flow cell as recited in claim 8 wherein said first tubular member is a hollow needle with said inlet defining an impaling portion.

11. The flow cell as recited in claim 8 wherein said manifold includes a central aperture and a perimeter surface disposed concentrically about said central aperture with a normal to said perimeter surface being perpendicular to said flow path, said plurality of bore holes extending from said central aperture, terminating in an opening proximate to said perimeter surface.

12. The flow cell as recited in claim 8 further including a means for clamping said manifold, said first tubular member and second tubular members to said transparent body.

13. The flow cell as recited in claim 8 wherein said second tubular member is cylindrical with a diameter matching the diameters of both said channel and said first tubular members, said channel, first tubular member and said second tubular member being coaxially aligned along an axis parallel to said flow path.

14. The flow cell as recited in claim 8 wherein said flow cell is a cylindrical cuvette having an outer surface defining an outer diameter, with the diameter of said channel and said outer diameter concentrically disposed about said axis.

15. A serum index sample probe for receiving a sample flow to be tested under the influence of an external light source, comprising: a cylindrical cuvette having first and second openings at opposed ends, and a cylindrical channel extending therebetween, defining a flow path; a first cylindrical member having two opposed ends with one end in fluid communication with said first opening and the remaining end proximally positioned with respect to said transparent body to receive a sample therethrough; a second cylindrical member having two opposed ends, with a first end in fluid communication with said second opening, with the remaining end distally positioned from said transparent body; and manifold means, positioned about said transparent body, for allowing transmission and detection of light over a plurality of fixed solid angles.

16. The serum index probe as recited in claim 15 wherein said manifold means includes a body having a central aperture, a perimeter surface disposed symmetrically about said central aperture and a plurality of bore holes, with a normal to said perimeter surface being perpendicular to said flow path and said plurality of bore holes extending from said central aperture, terminating in an opening proximate to said perimeter surface, said cuvette being received within said central aperture with said bore holes defining a plurality of optical paths to said channel.

17. The serum index probe as recited in claim 16 wherein said channel, said first tubular member and said second tubular member are cylindrical, having matching diameters, and are coaxially aligned along an axis parallel to said flow path.

18. The serum index probe as recited in claim 17 wherein said first cylindrical member is a hollow needle with said inlet defining an impaling portion.

19. The serum index probe as recited in claim 18 further including a means for clamping said manifold, said first tubular member and second tubular members to said transparent body.

20. The serum index probe as recited in claim 19 wherein said perimeter surface includes a plurality of flats equally spaced about said perimeter surface.