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Description  |
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BACKGROUND OF THE INVENTION
I. Field of the Invention
This invention relates generally to the analysis of materials, and more
particularly to a new arrangement for the end portion of a light guide
which directs light to to photospectormeter from a liquid sample located
in a cuvette. The present invention is particularly useful in automated
chemistry analyzers which are employed for determining the presence and
levels of one or more selected constituents in relatively small biological
liquid samples.
II. Description of the Prior Art
Numerous automated clinical analyzers are known and widely used in hospital
clinical laboratories. An example of such an analyzer is the multi-channel
type analyzer.
A multi-channel analyzer is one in which a series of different tests are
performed simulataneously by the analyzer, and in parallel with one
another. Such an analyzer can be best visualized as a series of batch
analyzers operating in parallel wherein each channel performs a single
analysis test. The multi-channel type analyzer generally utilizes a liquid
reagent to react with the particular constituent being tested in the
sample and a photo-optical system to read the optical absorbence of the
sample which corresponds to the level of the constituent in the sample.
Although this type of automated analyzer has received wide acceptance in
the clinical laboratory, certain drawbacks are associated with its use.
For example, although the multi-channel type analyzer is reliable due to
its simplicity, cost effective for large number of samples and has a
relatively high test throughout rate, it is limited in the sense that it
can only be effectively utilized to perform a single constituent analysis
at a time on a relatively large number of samples. In addition, such
analyzers are not capable of performing emergency "stat" tests due to
their relatively long and complex set up time and their inherent inability
to economically analyze a single test sample. Thus, the efficiency of this
type of system is not the best.
A further significant disadvantage found is that although tests can be
simultaneously performed for multiple constituents on the same sample,
generally all of these tests must be performed for every sample whether
desired or not. This results in waste of both sample material and the
reagents used in the unnecessary tests. Furthermore, due to the fact that
multiple discrete and dedicated channels are utilized in such an
instrument, there is significant duplication of numerous components which
adds to the complexity and expense of the overall instrument.
An automated single track clinical analyzer which avoids the
above-described drawbacks is described in commonly owned U.S. Pat. No.
4,528,157 entitled, "Automated Analysis Instrument System", the disclosure
of which is hereby incorporated by reference in its entirety. Furthermore,
by using a unique photo-optical system, described in commonly owned U.S.
Pat. No. 4,528,159 entitled, "Multichannel Spectrophotometer", the
disclosure of which is hereby incorporated by reference in its entirety,
greater flexibility of analysis at each analysis station is achieved. This
is because this photo-optical system employs fiber optic bundles or
similar light guides to transmit variable wavelengths of light to each
analysis station from a single light source.
The single track analyzer utilizes a disposable cuvette belt formed from
thin plastic film defining a series of discrete reaction compartments
(cuvettes) which are transported in line through the instrument. Such a
cuvette belt is described in commonly owned, abandoned U.S. patent
application Ser. No. 284,842, filed July 20, 1981 entitled, "Cuvette
System for Automated Chemical Analyzers". This belt provides hanbling
flexibility and avoids the cross-contamination associated with
flow-through cuvettes as well as avoiding the washing required for
reusable cuvettes.
In employing a photo-optical system for critical analysis work, it is very
important that there be substantially no interference with the path of
light that is directed from the sample being analyzed through a light tube
which in turn directs the light to a photospectrometer. Any interference
with this light path can effect the accuracy of the analysis, and lead to
incorrect results. However, it is typical of many of the prior art
analysis systems that a good deal of "noise" is received from the light
signal sent to a photospectrometer from a sample being analyzed. This
noise causes a scattering of the test results. Also, the test results tend
to "float". When using a series of photospectrometers in an analysis
system there is a tendency to avoid focussing of the light signal to the
photospectrometers thereby introducing tracing errors from one analyzer to
another analyzer. The end result of all of these problems is that the
level of accuracy of the analysis is reduced.
SUMMARY OF THE INVENTION
It is therefore an object of the present invention to overcome the
disadvantages of many of the analysis systems employing photo-optical
systems as disclsed by the prior art.
It is an object of the present invention to provide a photo-optical
analysis system that employs unique light guides to transmit various
wavelengths of light to each analysis station from a single light source.
It is to be noted that the term "light" as used herein should be
considered in its broadest sense to include both visible wavelengths and
non-visible spectral analysis wavelengths.
It is a further object of the present invention to provide a photo-optical
analysis system that employs a unique structure for the systems light tube
which substantially improves both the precision of the readings being
obtained and the accuracy of the analysis being sought.
It is a further object of the present invention to provide a photo-optical
analysis system that employs a unique structure for the systems light tube
that prevents any scratching or abrasion of the light tube by a passing
cuvette in which the sample being analyzed is contained.
It is still a further object of the present invention to provide a
photo-optical analysis system that employs a unique structure for the
systems light tube that prevents interference with the path of light from
the sample being analyzed to the photospectrometer by shortening the
amount (distance) of bath water that the light passes through in traveling
from the sample being analyzed to the light tube. This substantially
prevents the formation of bubbles or lodging of debris in the open space
area between the light tube and the cuvette containing the sample.
The foregoing objects and others are accomplished in accordance with the
present invention by providing an automated instrument system for
analyzing the constituents of a specimen sample wherein the sample is
contained in a cuvette and light is directed to the sample, into a light
guide and to a photo-optical system for analyzing the sample, the system
employing an improved light guide assembly. The improved light guide
assembly comprises a light guide having projecting at one end portion
thereof a quartz member and a housing for containing the end portion of
the light guide and the quartz member. The critical improvement of this
invention (which includes a light guide assembly as described herein that
can be used in an automated instrument system for analysis and which
avoids the disadvantages outlined above) lies in forming an aperture
between the quartz member and the housing, the aperture having a depth of
about 0.002 to 0.007 inches.
BRIEF DESCRIPTION OF THE DRAWINGS
For a better understanding of the invention as well as other objects and
further features thereof, reference is made to the following detailed
disclosure of this invention taken in conjunction with the accompanying
drawings wherein:
FIG. 1 is a schematic plan view of an automated clinical analyzer that can
incorporate the features of the present invention;
FIG. 2 is a partical perspective view of the automated clincial analyzer
shown in FIG. 1;
FIG. 3 is a perspective view of a cuvette belt for use in the clinical
analyzer of FIG. 1 and 2;
FIG. 4 is a partial schematic representation of a preferred photo-optical
system utilized with the analysis system of FIGS. 1 and 2;
FIG. 5 is a plan view of an end portion of a light guide assembly as
described in the prior art;
FIG. 6 is a plan view of an end portion of a light guide assembly in
accordance with the features of the present invention; and
FIG. 7 is a plan view illustrating the positioning of a cuvette between two
light guide end caps.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
FIGS. 1 and 2 illustrate as one example, an automated clincial analyzer 10
as generally described in commonly owned U.S. patent application Ser. No.
848,851, a continuation of Ser. No. 575,924, filed Feb. 1. 1984, now
abandoned and entitled "Clinical Analysis Systems and Methods", that can
incorporate the features of the present invention. More particularly, the
analyzer is Paramax Analytical System as manufactured by Baxter Health
Care Corporation. The analyzer 10 is particularly adapted for the testing
of constituents in biological fluids, such as blood samples.
The analyzer comprises a series of processing stations past which strips of
disposable reaction cuvettes are indexed or advanced. The cuvettes 24 are
supplied from a supply reel 20 as a continuous cuvette belt 22 and are
indexed through the analyzer by tractor conveyor 30 which engages a row of
index holes in the cuvette belt. The cuvettes are indexed in turn past the
following stations: a belt cutter 28 for dividing the belt into sections;
a tabletted reagent dispenser 40; a diluent and liquid reagent dispenser
50; an ultrasonic mixing horn 14; a sample dispenser 80 for dispensing
biological samples delivered by a transfer carousel 64; an air jet mixing
apparatus 15 including an apparatus for squeezing the top (opening) of the
cuvette during the air jet mixing process as described in commonly owned
U.S. patent application Ser. No. 858,366, filed Apr. 30, 1986 entitled,
"Improved Clinical Analysis Methods and Systems"; eight photometric read
stations 90; a further reagent dispenser 54; a further air jet mixing
apparatus 15a for mixing the sample and the further reagent; a cuvette
sealer 16 and a cuvette collection station 18. During their passage
through the analyzer, the cuvettes are carried in a water bath 12
maintained at a constant temperature.
The cuvette belt 22 is preferably constructed and made in the manner more
fully described in the aforesaid U.S. patent application Ser. No. 284,842.
As shown in FIG. 3, the belt 22 comprises two strips 111, 112 of
transparent flexible plastic material which are moulded and sealed
together to form a series of discrete, side-by-side parallel compartments
(cuvettes) 24 separated by webs 115. The compartments are closed at one
end and have a top or opening or open mouth 117 at the other end so as to
receive and retain fluid therein. For example, the cuvettes can be in the
order of size so as to be capable of holding about 500 microliters of
fluid. The flat web material 115 between the vessels 24 includes a
transport strip portion extending alongside the closed ends thereof which
is formed with indexing perforations or holes 26. These perforations are
engaged by the tractor transport 30 or the analyzer 10 for conveying the
cuvettes therethrough and maintaining a precise alignment of the optical
paths throug the cuvettes with the photo-optical examining system at
analysis stations 90.
The transport 30 comprises a single continuous guide and support track
extending through the analyzer having a main tractor belt 32 which engages
the indexing holes 26 in the cuvette belt 22 and advances the cuvettes
through the instrument at a predetermined rate of advance. A short loading
belt 34 threads the cuvette belt 22 into engagement with the main tractor
belt 32. The transport 30 advances or indexes the cuvettes through the
analyzer 20 in steps corresponding to the spacing between cuvettes (the
pitch of the belt) with the cuvettes being stopped and held stationary for
a dwell period between each advance. Each step may suitably correspond to
a time interval of 5 seconds with a 4 second dwell time between each
indexing advance of the cuvettes.
The reagent tablet dispenser carousel 42 comprises a circular array of
tabletted reagent dispensers 40 and can be rotated to bring the correct
solid reagent dispenser to solid reagent dispensing point "SRD" to drop a
single reagent tablet 44 into a cuvette 24. As illustrated, the carousel
42 accommodates thirty-two reagent tablet dispensers 40. It is rotated
under microprocessor control to bring the correct tablet dispenser to the
dispensing point for each cuvette. The dispensers 40 are detachable and
can be loaded randomly. An automatic flagging system indicates when a
dispenser is low in tablets.
The diluent and/or liquid reagent dispenser 50 is located adjacent to
carousel 42 for adding sufficient diluent 52 for reagent tablet 44
dissolution and/or for dispensing a liquid reagent into the reaction
vessel (cuvette) 24 at point "LDD".
The ultrasonic horn 14 acts on the cuvette contents for a sufficient length
of time; for example, 45 seconds, to totally dissolve the reagent tablets.
A sample loading and transfer carousel assembly 60 is located downstream of
the reagent and diluent dispensers. This carousel assembly comprises a
loading carousel 62 into which patient samples 70 are randomly loaded; a
transfer carousel 64 which accepts the patient samples 70 from loading
carousel 62, identifies the patient sample by means of a bar code reader
66 which reads a bar code label 72 placed on the patient sample container
and continuously feeds the patient samples into the system; and finally,
an unloading carousel 68 receives the patient samples 70 after testing and
stores them in an organized manner in the event that they must later be
located and retrieved.
The loading carousel 62 permits continuous random loading of up to 96
patient samples. The transfer carousel 64 continuously feeds patient
samples into the system for maximum throughput. Standard collection tubes
or micro samples tubes may be accommodated thus allowing utilization of
the same containers in which the sample is collected; for example, in the
case of blood samples, the "Vacutainer" tube which is commonly used to
draw the serum specimen.
Sample 80 for dispensing samples into the cuvettes 24 at point "SD" is
located adjacent to transfer carousel 64. This sampler is designed to
aspirate about 2 to 20 microliters of patient sample 70 from its container
in the transfer carousel and dispense it into a cuvette 24 during the four
second dwell period while the cuvette is aligned with the angler.
The air jet mixing apparatus 15 (and 15a) direct an air jet preferably at
an acute angle against the liquid surface in the cuvette adjacent its
junction with the cuvette wall to create a vortex thus producing a
thorough mixing of the sample with the reagent and diluent in accordance
with the teachings of the system as described in the aforesaid U.S. patent
application Ser. No. 848,821. In a preferred embodiment, the apparatus has
a fixed, inclined nozzle and the cuvettes 24 are aligned in position
beneath the nozzle and the air jet is switched on only during the dwell
period when the cuvette is stationery. In order to ensure that the air jet
correctly strikes the liquid surface, the liquid level is closely
controlled.
Eight photometric analysis stations 90 are located at points "SA1" through
"SA8" along the cuvette track 30. These analysis stations are connected by
individual optical guides 92 and 94 to photo-optical system 100. The
station "SA1" is arranged following the ultrasonic horn 14 for verifying
proper reagent dispensing and dissolution. This system is illustrated in
FIG. 4.
The photo-optical system comprises a single light source 101 for generating
selected wavelengths of light. The output of light source 101 is focused
by fixed focusing lens 102 onto the multiple wavelength selective filters
disposed about the circumference of rotary source filter wheel 103. The
rotation of source filter wheel 103 is regulated by the instrument control
microprocessor through double shafted motor 104. The output from source
filter wheel 103 is sequentially transmitted through separate light guides
92 to each of the analysis stations.
At the analysis stations, the filtered light energy is passed through the
reaction compartment 24 containing the mixture to be analyzed. The output
of the analysis stations is then passed back to the photo-optical system
100 via separate light guides 94. At this point, a second filter wheel
107, which preferably is identical to and synchronized with source filter
wheel 103, intercepts the outputs of light guides 94 before this output is
directed to a separate photodetector tube 109 for each analysis station. A
reflector may be utilized to focus the output of filter wheel 107 on
photodetector tubes 109. In the representation of FIG. 4, only one set of
light guides 92, 94 and one photodetector tube 109 is shown for
simplicity, although it is to be understood that eight of these elements
(one for each analysis station) are required.
The outputs of photodetector tubes 109 are monitored by the control
microprocessor and appropriate wavelength output values for each analysis
reaction at each analysis station is stored by the microprocessor. When
the reaction is completed, the microprocessor will utilize this stored
information to calculate the concentration of the selected sample
constituent and provide this result to the instrument operator.
As can be seen from FIG. 4, each filter wheel has seven different
wavelength selective filters 105 disposed about its circumference. In
addition, an opaque blank 106 is located thereon in order to establish the
residual "dark current" level of the electronics. Hence, great flexibility
is provided by permitting any one or combination of the seven wavelengths
to be read at any analysis station for any sample during the four second
analysis period. In that filter wheels 103, 107 are rotated at thirty
revolutions per second in the preferred embodiment, thirty readings at a
particular wavelength may be made each second which can then be averaged
to provide a highly accurate final value by the microprocessor.
The second reagent dispenser 54 permits further reaction of the sample to
be obtained following initial testing and is shown arranged between
analysis stations "SA4" and "SA5". It could be located between any of the
analysis stations "SA2" to "SA8". This capacity for optional reagent
additions or triggered reaction capability gives added analytical
versatility for multiple reagent test situations.
The further air jet mixing apparatus 15a provides for thorough remixing of
the cuvette contents following addition of further reagent at station 54.
The cuvette sealer 16 seals the tops of the tested cuvettes for convenient
clean disposal of completed samples at the cuvette disposal location where
they are neatly collected into a lined disposal bin.
The microprocessor control system of the clinical analyzer, which suitably
has a 280 processing unit, controls all the operating units thereof in
accordance with sample and test information inputted at a suitable
operator interface keyboard. In accordance with the desired test results,
quantities of a single sample may be dispensed into one or more cuvettes
either alone or in combination with any one or more of the solid and
liquid reagents and diluents, and examined at any one or more of the
analysis stations 90. Test results are displayed on a screen and can be
printed out.
Turning now specifically to the unique features of the present invention,
there is shown in FIGS. 5 a typical end portion of a light guide assembly
as described in the prior art. In comparison there is shown in FIG. 6 an
end portion of a light guide assembly in accordance with the features of
the present invention suitable for use as the end portion of optical
guides 92 and 94 (see FIG. 4) in the automated clinical analyzer described
above at analysis station 90.
The prior art generally describes light guide assemblies for clinical
analyzers that employ end caps and liquid light tubes having the basic
configuration as illustrated in FIG. 5. A known assembly includes a light
guide in the form of a liquid light tube 150 that is encased by a housing
151 up to the end cap area. The end cap is joined onto the liquid light
tube 150 and contains a quartz member 152 and an aperture 153. Since the
entire assembly is immersed in a water bath (this is typical of this type
of light guide assembly when used in a clinical analyzer as described
hereinabove), the water fills the aperture and space inside the end cap
leading up to the end face of quartz member 152. During the analysis
procedure, light is passed through a cuvette having the sample being
analyzed therein, through the length of bath water in the aperture 153,
into and through the quartz member 152 and into and through the light tube
150. Specifically, because of the aperture arrangement and the length
(distance) the light must travel in the water to get from the sample in
the cuvette to the quartz member, there is a great tendency to form
bubbles and trap debris in the aperture. Both the bubbles and the debris
substantially interfere with the critical accuracy of the analysis. The
prior art light guide assembly introduces a good deal of noise in the
signal that is received by the photospectrometer which causes scattering
of the test results. Also, the test results tend to float thereby
descreasing the overall accuracy of the analysis results.
The problems and disadvantages of the prior art light guide assembly as
described hereinabove have been overcome by the light guide assembly
having the features of the present invention and as shown in FIG. 6. The
light guide assembly in accordance with the present invention includes a
light guide in the form of a light tube 155 that is encased by a housing
156 up to the end cap area. It is preferred that the light tubes employed
are commercially available liquid light tubes. Installed on the end of the
light tube 155 is quartz end member 157. The purpose of the quartz end
member is to provide a wear-resistant component relative to the bath water
which is not biodegradable and which has excellent optical
characteristics. The quartz member provides all such advantages. It was
recognized and appreciated by the present invention that placement of
quartz member 157 relative to the end cap (and cuvette) was critical to
the accuracy of the clinical analyzer which employed such a light guide on
its optical guides (e.g. light guides 92 and 94 of FIG. 4).
The light guide assembly shown in FIG. 6 places the cuvette end of the
quartz member up against the back side of the wear plate 158 of the end
cap and thereby provides an aperture 159 having a depth that is kept
between 0.002 and 0.007 inches; which distance is critical to the present
invention. By placing the end of the quartz member close to the inside of
the end cap, the path of light through the bath water is precisely limited
to the depth of the aperture, i.e. 0.002 to 0.007 inches. By maintaining
this critical aperture depth in the light guide assembly during the
analysis process, a dramatic improvement in the accuracy of the
photospectrometer test results is achieved from analysis machine to
analysis machine. This is provided by a combination of the accurate
control of the size of the aperture depth in the light guide end cap and
the resulting short length of bath water that the light path must pass
through between the cuvette wall and quartz member 157.
As shown in FIG. 7, during the analysis process cuvettes 160 pass through a
channel formed by two light guide end caps 161 and 162 (each of which
incorporate the features of the present invention) when the fluid in the
cuvette is read by the photospectrometer. Cuvette walls are generally
formed in a convex manner (outwardly shaped). To remove any space between
the end caps 161 and 162 and each cuvette 160, and insure improved length
control (thereby preventing interference with the accuracy of the readings
by the photospectrometer) the cuvette walls are made parallel to each
other by the end caps. This arrangement enables the cuvette walls to be
aligned horizontally by the light guide end caps and vertically by the
index holes (item 26 of FIG. 3) in the cuvette belt during analysis. In
accordance with the preferred features of the present invention in order
to provide a high level of accuracy with regard to the analysis results,
the distance A between the light guide and caps 161 and 162 during
analysis should be preferably maintained at about 0.195 inches +0.001 to
keep the cuvette walls substantially flat and thereby improve the accuracy
of the analysis.
By employing such a precise geometric arrangement of the cuvettes between
the light guide end caps in accordance with the critical features of the
present invention, all of photospectrometers act as one photospectrometer
Furthermore, by shortening the depth of the light guide end cap and
therefore the amount (distance) of bath water that the light passes
through in accordance with the critical parameters described hereinabove,
there is basically no chance that bubbles or debris will be present or get
trapped in the aperture. Providing the critical geometric structure to the
light guide end cap in accordance with the present invention would provide
for each analyzer in a clinical analysis system as described hereinabove
to be so focused automatically with regard to the light signal thereby
substantially eliminating tracking error from analyzer to analyzer.
It should be understood that the above described embodiments of the
invention are illustrative only, and that modifications thereof may occur
to those skilled in the art. Accordingly, this invention is not to be
regarded as limited to the embodiments disclosed herein, but is to be
limited only as defined by the appended claims.
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Description  |
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