Method and apparatus for automatic processing and analyzing of blood serum

An apparatus for processing and analyzing blood serum includes an input rack for holding test tubes containing whole blood specimens and separator gel, a centrifuge, an optical sensing unit for receiving centrifuged test tubes and generating output signals indicative of whether the centrifuging was successful and, if it was, the boundary position between the separator gel and the blood serum, and a computer connected to receive and analyze the output signals of the optical sensing unit. An aspirator/dispenser needle unit is positioned above the sensing unit and is capable of lowering a needle, under the control of the computer, to puncture the stopper of a test tube and then withdraw blood serum. The apparatus also includes a cup feeder station for storing and dispensing empty cups for receiving and holding blood serum dispensed from the needle, an noutput rack for holding cups containing blood serum samples along with the corresponding test tubes, a bar code reader for identifying test tubes, and a disposal station for receiving test tubes determined to be defective by the computer. A robotic arm moves the tube from station to station under the control of the computer.

BACKGROUND OF THE INVENTION 
A. Field of the Invention 
This invention relates to apparatus and a method for processing and 
analyzing blood serum and more particularly to a system that automatically 
processes whole blood specimens to separate and withdraw the blood serum 
from the red blood cells and that also removes from further processing 
those specimens which are defective before the blood serum is withdrawn. 
B. Description of Related Art 
The process of separating the red blood cells from the blood serum of a 
whole blood specimen by centrifuge and then removing the blood serum is 
conducted on a large scale in hospitals and laboratories. This process is 
usually conducted manually by a technician. In the process, a stopper 
sealed test tube, containing a whole blood specimen and a separating gel, 
is centrifuged so that its contents are separated into three layers, a top 
layer containing the serum, a middle layer containing the separating gel, 
and a bottom layer containing the red blood cells. After the test tube is 
centrifuged, the technician must examine the blood specimen to determine 
whether it is defective. If the sample is not defective, the technician 
then inserts a needle through the rubber stopper, eyes the placement of 
the needle in order to insure the needle does not contact the separating 
gel, and withdraws a sample of the blood serum from the top layer and 
places the sample into a cup. Efficiency, accuracy, and maintaining the 
integrity of the blood specimen are essential to this process. More 
important is the safety of the technician while completing the process. By 
fully automating this process, these factors are greatly enhanced. The 
danger to the technician of being exposed to any transmitted diseases in 
the specimens during this process is eliminated. 
U.S. Pat. Nos. 4,713,974 and 4,478,095 disclose devices for automatically 
piercing container lids and withdrawing samples. Neither of these patents 
disclose any means for sensing an appropriate level inside the test tube 
for positioning the tip of the sampling needle. Also, these patents do not 
disclose devices for use with centrifuged blood samples and do not 
disclose any means for automatically detecting defective samples. 
U.S. Pat. Nos. 4,120,662 and 4,311,484 both disclose blood sample 
processing systems for delivering blood from closed vacutainers to a 
Coulter Counter. These systems are not suitable for use with centrifuged 
blood samples in that tubes are sampled in an approximately horizontal 
position and are agitated prior to sampling. 
U.S. Pat. No. 4,326,851 discloses a level sensor for use with a fluid 
transfer mechanism for determining when the bottom tip of a fluid 
aspirating probe touches the top surface of a sample fluid. This device 
cannot be used with blood samples in conventional test tubes. In addition, 
the patent discloses no method or apparatus for automatically sensing 
whether the sample is defective. 
SUMMARY OF THE INVENTION 
This invention is accordingly directed toward apparatus and a method for 
automatically centrifuging blood specimens and separating gels in stopper 
sealed test tubes, determining whether the centrifuged specimens are 
defective, and removing and then dispensing blood serum samples from only 
those sealed test tubes in which the specimens are not defective. 
The method of the present invention includes centrifuging a test tube 
containing a whole blood specimen and separator wax, moving the test tube 
into an optical sensing unit, and analyzing the electrical signals 
generated by the sensing unit to evaluate the success of the separation 
and to determine the position of the boundary surface between the 
separator wax and the blood serum. 
In the preferred embodiment, the optical sensing unit includes a vertical 
cavity operative to receive a test tube. The cavity includes a light 
source disposed on one of its sides that emits a light beam that extends 
generally normally to the longitudinal axis of a test tube placed in the 
cavity. The cavity also includes at least one photosensor disposed on its 
opposite side and positioned to receive the transmitted portion of the 
light beam. The photosensor generates electrical signals proportional to 
the amplitude of the transmitted beam. The apparatus of the present 
invention further includes means for receiving these electrical signals 
and analyzing them to evaluate the success of the separation, and to 
determine the position of the boundary surface between the separator wax 
and the blood serum along the longitudinal axis of the tube. 
In an alternative embodiment, the vertical cavity of the optical sensing 
unit includes a vertical array of photosensors disposed on one side of the 
cavity and a corresponding vertical array of light sources disposed on the 
opposite side of the cavity. Each of the plurality of light beams emitted 
from the light sources extend generally normally to the longitudinal axis 
of a test tube placed in the cavity. The photosensors each receive the 
light beams transmitted from their corresponding light sources and 
generate electrical signals proportional to the amplitude of the 
transmitted beams. 
The apparatus of the present invention also includes an input station 
adapted to hold test tubes each containing whole blood specimens and 
separator wax, and a centrifuge for separating the whole blood into serum 
and red cells separated by a layer of separator wax. 
The apparatus further includes a needle apparatus, responsive to the means 
for determining the position of the boundary surface between the separator 
wax and the blood serum, connected to suction means for insertion into a 
test tube and for drawing a blood serum sample from the tube. The needle 
apparatus is also connected to means for dispensing the serum that was 
drawn out of test tubes by the suction means. 
The apparatus also includes a pair of output stations for receiving both 
successfully and unsuccessfully separated test tubes, and a robotic arm 
for moving the test tubes from station to station, under the control of 
the means for evaluating the electrical signals generated by the 
photosenor(s). 
The preferred embodiment also includes a feeder station adapted to dispense 
empty containers that are operative to hold blood serum samples. The 
robotic arm is also adapted, under the control of the means for evaluating 
the electrical signals generated by the photosensor(s), to remove an empty 
container from the feeder station and to move it to a position underneath 
the needle apparatus. 
The present invention makes the process of centrifuging and analyzing blood 
specimens efficient and accurate. It also eliminates the danger of a 
technician being exposed to any transmitted disease, such as AIDS, during 
the process.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
Referring to FIG. 1, the preferred embodiment of the present invention is 
supported on a work station 11. In FIG. 1, a robotic arm, generally 
indicated at 10, is positioned so that it can axially rotate about a 
vertical axis to reach any of six different stations. The robotic arm is 
connected to a control computer 12. In the preferred embodiment, the robot 
is a five axis articulated arm. Such robotic arms are well known to the 
art. The robotic arm 10 includes a multi-purpose gripper 14 of 
conventional construction. 
The first station constitutes a rack 16 for holding test tubes 18 of 
conventional construction. The rack may be either manually loaded by an 
operator, or automatically loaded. In the preferred embodiment each test 
tube is bar coded for identification purposes. The bar code is read either 
by the robot 10 or by equipment at the hospital or clinic where the blood 
was drawn. The second station is a centrifuge 20. The centrifuge is used 
to centrifuge whole blood specimens along with separating gels in stopper 
sealed test tubes by rotating the tubes inclined with respect to a 
vertical axis about that axis so that the contents of the test tubes are 
separated, as indicated in FIG. 2, into a top layer 40 containing the 
blood serum, a middle layer 42 containing the separating gel, and a bottom 
layer 44 containing the red blood cells. The separator gel (or wax) has a 
density half-way between the densities of the serum and the red blood 
cells. As indicated in FIG. 2, after centrifuging the separator gel may 
not lie in a horizontal plane normal to the longitudinal axis of the test 
tube, but rather at an angle from the horizontal plane. The orientation of 
the middle layer 42 is determined by the type of centrifuge used. 
Centrifuges are well known to the art. 
The third station is a serum sensing and aspirator/dispenser unit, 
generally indicated at 22. This station includes an optical blood serum 
sensing unit 24, and an aspirator/dispenser unit 26. The station 22 also 
includes a bar code reader 28 of conventional construction. Both the 
sensor and the aspirator/dispenser units are connected to the control 
computer 12. The optical sensor 24 receives test tubes containing 
centrifuged blood specimens and outputs signals to the computer 12 so that 
the computer may determine whether the specimen is defective, and, if it 
is not, an appropriate level in the test tube to position the tip of an 
aspirator needle for removing a blood serum sample. The 
aspirator/dispenser unit 26 functions, under the control of computer 12, 
to lower a sampling needle 30 to puncture the stopper seal of a test tube 
held in the optical sensor 24, for withdrawing samples from the test tube. 
Automatic aspirator/dispensers are well known to the art. 
The fourth station is a serum cup feeder 32 that stores empty cups 33 for 
holding blood serum samples dispensed by the aspirator/dispenser unit 26. 
The serum sample cup is preferably formed of plastic. The fifth station is 
an output rack 34 for holding cups containing blood serum samples along 
with their corresponding test tubes. Finally, the sixth station is a 
rejection unit 36 for receiving those test tubes which are determined 
defective by the computer 12. 
The preferred embodiment of the present invention operates, under the 
control of computer 12, as follows: 
First, the robotic arm 10 loads test tubes, each containing whole blood 
specimens and separating gel, into the centrifuge 20 one by one from the 
input rack 16. The centrifuge 20 is then activated. After the centrifuging 
process is completed, the robotic arm 10 removes the centrifuged test 
tubes, one by one, from the centrifuge 20 and places them into the optical 
sensor 24. 
If the signals from the optical sensor 24 indicate that the centrifuging 
results in lipemic (white), hymolized (red) or otherwise unsuccessful 
specimen, then the robotic arm 10 removes the test tube from the sensor 24 
and places it in the rejection unit 36. 
If the signals from the optical sensor 24 indicate the specimen is not 
defective, the sampling needle 30 of the aspirator/dispenser unit 26 is 
lowered to puncture the stopper seal of the test tube and to the level in 
the test tube previously determined by the analysis of the output signals 
from the optical sensor 24. A sample of the blood serum is drawn from the 
test tube through the needle 30 by the aspirator unit. In the preferred 
embodiment of the invention, approximately 1.5 milliliters of blood serum 
is withdrawn. 
At the same time that the blood serum is being withdrawn, the robotic arm 
10 removes an empty serum cup from the serum cup feeder 32, using the 
gripper 14. After the blood serum sample is withdrawn from the test tube, 
the aspirator/dispenser unit 26 lifts the sampling needle 30 out of the 
test tube into a stow position. The robotic arm 10 then moves the empty 
serum cup into a position underneath the sampling needle 30. The 
aspirator/dispenser unit 26 then dispenses the blood serum sample through 
the sampling needle 30 and into the cup that is supported by the robotic 
arm 10. 
After the cup receives the blood serum sample, the robotic arm places the 
cup on top of the stopper seal of the test tube resting in the optical 
sensor 24. The robotic arm 10 then removes the test tube, along with the 
serum sample cup, from the optical sensor 24, positions it by the bar code 
reader 28 for identification purposes, and places the test tube along with 
the serum sample cup in the output rack 34. In the preferred embodiment of 
the invention, the serum sample cup is constructed so as to snugly fit on 
top of a stopper. 
The above process is repeated until all centrifuged test tubes are 
examined. The system may then load a new batch of test tubes into the 
centrifuge. 
FIG. 3 is a cross-sectional view of the optical sensor 24 of the preferred 
embodiment of the present invention. The sensor 24 is located in a 
vertical cavity, generally indicated at 50, of a housing 52. The vertical 
cavity 50 has an opening 54, and is adapted to receive a test tube of 
conventional construction. The sensor 24 is connected to a power source 
via a power cord 55. 
A light source 56 is disposed on one side of the cavity 50, near the 
opening 54. The beam emitted by the light source 56 extends generally 
normally to the longitudinal axis of a test tube placed in the cavity 50. 
In the preferred embodiment, the light beam is a pulsed infrared 
rectangular sliver of light extending across the diameter of the cavity 
50. The beam is pulsed at a high frequency to avoid ambient noise. 
A sensor 58 is disposed on the opposite side of cavity 50 from the light 
source 56 so as to receive the transmitted portion of the light beam 
emitted from the light source. In the preferred embodiment, the sensor is 
a horizontal array of photosensors adapted to receive the entire sliver of 
light when the cavity is empty. Optical filters that only transmit light 
having the frequency of light source 56 are positioned in front of the 
photosensors in order to avoid noise. The contents of a test tube 
displaced between the light source 56 and the sensor 58 will partially 
occlude the light beam from the sensors. The sensors have an analog output 
proportional to the portion of the beam that is occluded. The sensor 58 is 
connected to the control computer 12 via a connection line 60 in order to 
provide it with the outputs of the photosensors. In the preferred 
embodiment, the output from photosensors is passed through an analog to 
digital converter before being received by the computer 12. 
The control computer 12 processes the signals received from the optical 
sensor 24 in order to determine the success of the centrifuge separation 
and the level of the separator wax (the middle layer) in the centrifuged 
specimen. In the preferred embodiment of the present invention, the 
robotic arm 10 is controlled to lower the centrifuged test tube to be 
analyzed down through the opening 54 and into the cavity 50 of the optical 
sensor 24. While the robotic arm 10 is moving the tube down into the 
cavity 50, the computer 12 receives the output signals from the sensor 58. 
If a successfully centrifuged blood specimen, as indicated in FIG. 2, is 
being moved into the cavity 50, first the light beam is occluded to a 
relatively high degree by the bottom layer 44 of red blood cells, then to 
a lesser degree by the middle layer 42 of separator wax, and then to an 
even lesser degree by the top layer 40 of blood serum. 
If the output signals from the optical sensor 24 do not indicate these 
three layers, then the robotic arm removes the test tube from the optical 
sensor and places it in the rejection unit 36. In the case where the 
centrifuging is successful, knowledge of the position of the test tube 
relative the optical sensor at the point in which the sensor 58 signals 
indicate a transition between the separator wax and the blood serum allows 
the computer 12 to determine a level, spaced above the separator wax, for 
positioning the sampling needle 30 of the aspirator/dispenser unit 26. 
FIG. 6 is a general flow diagram for the algorithm used by the computer 12 
in evaluating the outputs from the optical sensor 24 in the preferred 
embodiment of the invention. For the purposes of illustration, well-known 
housekeeping functions, such as error checking features, have been omitted 
from the flow diagram of FIG. 6. 
The algorithm makes use of the following variables: 
DEFECT: boolean variable for indicating whether the specimen is defective; 
LAST: indicates the which portion of the centrifuged blood sample was last 
in between the sensor and the light source--X (for initialization), RB 
(for red blood cells), SEP (for separation wax), and BS (for blood serum); 
TRANSITION: boolean, set to true when sensor first detects blood serum; 
OCCL: variable for reading in amount of occlusion sensed by sensor 58; 
RBMIN, RBMAX: constants representing the minimum and maximum values of OCCL 
that would indicate red blood cells; 
SEPMIN, SEPMAX: constants representing the minimum and maximum values of 
OCCL that would indicate for separator wax; 
BSMIN, BSMAX: constants representing the minimum and maximum values of OCCL 
that would indicate for blood serum; 
CURR: same type as LAST, for storing the current portion of the centrifuged 
blood serum between the sensor and the light source; 
POSITION.Z: for storing the vertical position of the robot gripper; 
FACTOR: a constant; 
REFERENCE: vertical position of robot gripper when holding a test tube that 
is fully placed in the optical sensor; and 
SENSOR.Z: vertical position of the sensor 58. 
First, the algorithm initializes DEFECT to false, LAST to X, and TRANSITION 
to false. Next, at the step indicated at 100, it is checked whether DEFECT 
is false, the robot arm is moving the tube into the sensor, and TRANSITION 
is false. If one of the above conditions is not true, then the algorithm 
goes to the step indicated at 114. Otherwise, the algorithm continues at 
step 102. 
At 102, the output from sensor 58 is read into the variable OCCL. Then, it 
is checked whether the value of OCCL is in the range that indicates the 
sensors are detecting red blood cells. If it is not, the algorithm goes to 
the step indicated at 104. If the sensor is detecting red blood cells, 
CURR is set to RB and it is checked whether the last sensor read indicated 
separator wax or blood serum. If not, the algorithm skips to the step 
indicated at 110. If the variable LAST is set to either SEP or BS, then 
the algorithm goes to the step indicated at 108. 
At 104, it is checked whether the variable OCCL is set to a value 
indicative of separator wax. If not, the algorithm continues at the step 
indicated at 106. If so, CURR is set to SEP, and it is checked whether 
LAST is set to X (just initialized) or BS (the last sensor read indicated 
blood serum). If LAST is not set to either of these values, the algorithm 
continues at the step indicated at 110. If LAST is set to either X or BS, 
the algorithm goes to step 108. 
At 106, it is checked whether OCCL is set to a value indicative of the 
sensors detecting blood serum. If not, the algorithm skips to step 108. If 
so, CURR is set to BS, and it is checked whether LAST is set to either RB 
or X. If not, the algorithm skips to step 110. If, however, LAST is set to 
either RB or X, the algorithm skips to step 108. 
At step 108, DEFECT is set to true. Next, the algorithm continues at the 
step indicated at 100. 
At step 110, it is checked whether both CURR is set to BS and LAST is set 
to SEP. If not, the algorithm continues at the step indicated at 112. If 
so, POSITION.Z is set to the vertical position of the robot gripper and 
TRANSITION is set to true. The algorithm then continues at step 112. 
At 112, LAST is set to CURR, and the algorithm jumps back to step 100. 
At 114, it is checked whether either DEFECT is true, or transition is 
false. If so, the centrifuged blood specimen is defective and a routine 
for controlling the robotic arm to dispose of the defective test tube is 
called. If both DEFECT is false and TRANSITION is true, then POSITION.Z is 
set to FACTOR +REFERENCE-(POSITION.Z-SENSOR.Z). This is the desired 
vertical position for positioning a sampling needle in the test tube for 
withdrawing blood serum. Next, a routine is called to control the 
aspirator/dispenser unit to withdraw the blood serum. 
The description of the above algorithm is not intended to limit the present 
invention. Many different algorithms may be implemented for the purposes 
of the invention. In alternative embodiments, the sensor and analyzing 
algorithm may be further adapted to sense discolorizations in the specimen 
that would indicate an unsuccessful centrifuging. 
FIG. 5 is a cross-sectional view of an optical sensor unit that may be 
utilized in an alternative embodiment of the present invention. A housing 
80 contains a vertical cavity, generally indicated at 82. The cavity 82 
has an opening 84 and is adapted to receive a test tube of conventional 
construction. The housing 80 is connected to a power source via a power 
cord 85. 
A vertical array of light sources, indicated at 86, is disposed on one side 
of the cavity 82 and extends from the top of the cavity, near the opening 
84, to the bottom. Each light source emits a light beam that extends 
generally normally to the longitudinal axis of a test tube placed in the 
cavity 82. 
A corresponding vertical array of photosensors, indicated at 88, is 
disposed on the opposite side of cavity 82 from the vertical array of 
light sources 86. Each of the photosensors is adapted to receive the light 
beam transmitted from its corresponding light source and then generate 
signals proportional to the amplitude of the transmitted beam. The signals 
outputted by the sensors are provided to the computer 12 via connection 
line 90. 
In this embodiment, the computer 12 analyzes the signals generated by each 
photosensor after a test tube is placed into the cavity 82 by the robotic 
arm 10. If the signals do not indicate that the blood specimen is 
separated into three different layers, then the sample is defective and 
the robotic arm 10 is controlled to remove the test tube from the sensor 
24 and place it in the rejection unit 36. If the centrifuge was 
successful, the computer 12 determines a level in the test tube to 
position the sampling needle by locating the lowest photosensor in the 
array 88 that is generating signals indicative of the blood serum layer. 
FIG. 4 is a side view of the aspirator/dispenser needle unit of the 
preferred embodiment of the present invention. A vertically oriented 
sampling needle 70 is connected to an extendible vertical arm 71 that is 
supported on an overhead arm 73 by a vertical post 75. The needle 70 is 
connected to an aspirator/dispenser 72 of conventional construction by a 
tubing 68. In the preferred embodiment, the needle 70 is positioned 
directly above the cavity 50 of the optical sensor 24 so that when 
lowered, the needle 70 may puncture the stopper seal of a test tube 
resting in the cavity through its center. 
The extendible vertical arm 71 is connected to a motor 74 disposed on the 
overhead arm 73, that controls the vertical position of the needle 70, and 
may lower the needle into a stopper sealed test tube that is positioned in 
the optical sensor 24. The overhead arm 73 is also capable of moving 
laterally to ensure proper positioning of the sampling needle 70 in 
relation to a test tube below it. The motor 74 and the aspirator/dispenser 
72 are connected to the computer 12 via connection lines 77 and 76, 
respectively. The motor 74 and extendible vertical arm 71 are of 
conventional construction and controlled by input signals transmitted by 
the computer 12 through the connection line 77. In an alternative 
embodiment, the overhead arm 73 may be extendible so that the horizontal 
position of the needle may also be adjusted. 
The preferred embodiment of the present invention also includes a bar code 
reader 78. The reader 78 is positioned so that the robotic arm 10 may 
place a bar coded test tube in front of it. The bar code reader 78 is 
connected to the computer 12 by connection line 79 so that the computer 
controls when the reader is activated. The computer 12 also receives the 
information obtained by the activated reader 78 via the connection line 
79. In the preferred embodiment, the bar coded test tubes containing whole 
blood specimens and separator gel are initially loaded into the input rack 
16 in a predefined orientation, so that the robotic arm 10 may properly 
place the processed tubes in front of the bar code reader 78. Alternative 
embodiments may not include a bar code reader and therefore may not 
require the test tubes to be initially loaded into rack 16 in 
predetermined orientations. 
The above description is not intended to limit the present invention. It is 
understood that it is possible to make modifications and variations in 
light of the above teachings without departing from the present invention.