BACKGROUND

The present invention is directed to a device and method for detecting the presence of a flow restriction, i.e., a clot in pipetting for a diagnostic system.

Diagnostic systems are commonly used to analyze blood samples for the presence of illness or disease. Diagnostic systems typically utilize a probe connected with pipetting to a motorized syringe to withdraw a predetermined amount of a blood sample from a collection tube containing the blood sample. After the predetermined amount is withdrawn, a crane moves the probe from the collection tube to a reaction cup and the sample is expelled into the reaction cup for testing.

However, obstructions in the probe and/or pipetting, i.e., clots in the blood sample, can adversely affect the precision of the predetermined amount of the sample being transferred to the reaction cup. If the incorrect amount of sample is tested, the diagnostic system may reach an incorrect result. This problem is becoming even more prevalent with automated diagnostic systems which are operated without supervision.

Thus, it has become necessary to detect flow restrictions in the pipetting and the probe to ensure that the proper amount of sample is being tested.

One attempt to solve this problem involves plumbing a side connection into the pipetting and connecting a pressure transducer to the side connection. The pressure transducer is used to detect a change of pressure in the pipetting which indicates a flow restriction. However, this attempt is not always satisfactory since the side connection can retain air and contaminates which can contaminate the sample and adversely affect the diagnosis. Further, a portion of the sample can be retained in the side

- connection thereby reducing the amount of sample being transferred to the reaction cup. Moreover, since the pressure transducer connects directly into the pipetting, the pressure transducer directly contacts the sample being tested . Therefore, there is a possibility that the pressure transducer and/or the sample being tested can be adversely affected by such contact.

Accordingly, there is a need for a device for detecting the presence of a flow restriction in pipetting which does not require side connections which can contain contaminants and air and/or retain a portion of the sample. Further, there is a need for a device which does not directly contact the sample.

SUMMARY The present invention is directed to a device for detecting a change of pressure in pipetting which meets these needs. A device for detecting a change of pressure in pipetting transporting a fluid sample for a diagnostic system according to the present invention includes a hollow conduit for transporting the fluid sample, a housing, a substantially incompressible medium, and a sensor. As detailed below, the device detects a pressure increase in the pipetting without the need for side connections in the pipetting and without direct contact between the substance and the sensor.

The conduit has a substantially constant internal cross-sectional area and includes a flexible section which is typically a thin-walled section of elastomer tubing. The housing is substantially rigid and has an internal cavity which substantially encloses the flexible section and forms a substantially sealed internal chamber around the flexible section. The substantially incompressible medium is disposed within and fills the internal chamber. The sensor, typically a pressure transducer, is in communication with the substantially incompressible medium and detects a change of pressure in the medium.

The invention also includes a method for detecting a change of pressure in pipetting transporting a fluid sample, the pipetting including a flexible section. The method includes enclosing the flexible section with a sealed internal chamber filled with a substantially incompressible medium and sensing an increase of pressure in the internal chamber with a sensor.

As discussed below, a flow restriction in the conduit causes a decrease in pressure in the conduit which causes the thin-walled flexible section to contract. The contraction of the flexible section results in a decrease of pressure of the substantially incompressible medium in the chamber which is detected by the sensor. Thus, the present invention detects a change of pressure in the conduit without side connections in the conduit which change the internal cross-sectional area of the conduit and which can contain contaminants or air which adversely affect the integrity and the amount of the substance being transferred. Additionally, since the sensor is in communication with the incompressible medium instead of the substance being transported by the conduit, there is no chance of adverse reaction between the sensor and the substance.

DRAWINGS These and other features, aspects and advantages of the present invention will become better understood from the following description, appended claims and accompanying drawings where:

Figure 1 is a front, partial cut-away view of a device for detecting a change of pressure in a conduit having features of the present invention;

Figure 2 is a front, exploded and partial cut-away view of the device of Figure 1 ;

Figure 3 is a rear plan view of the device of Figure 1 ; and Figure 4 is a side plan view of a diagnosis system including the device of Figure 1 .

DESCRIPTION A device 10 for detecting a change of pressure in pipetting transporting a fluid sample according to the present invention comprises (i) a hollow conduit 12 capable of transporting a fluid sample 14; (ii) a housing 16;

(iii) a substantially incompressible medium 18; and (iv) a sensor 20.

As shown in Figure 4, the device 10 for detecting a change of pressure in the conduit 12 is useful for detecting a flow restriction (not shown) in pipetting and a probe 21 for a diagnostic system 22. A suitable diagnostic system 22 is sold by Beckman Instruments, Inc., located in Brea,

California. A suitable probe 21 is disclosed in U.S. Patent No. , titled "Vented Probe and Method for Adding and Removing a Sample From A

Container", filed October 20, 1 995, which is incorporated herein by reference.

Alternatively, the present invention is particularly useful for applications where the fluid sample 14 can be contaminated by air or contaminants in a side connection, where the precise amount of fluid sample 14 being transported is critical or where it is undesirable to have direct contact between the sensor 20 and the fluid sample 14.

The fluid sample 14 is a liquid that is transportable through the conduit 12. For diagnostic systems 22, the fluid sample 14 is usually a blood sample or urine sample.

Typically, the conduit 12 is a hollow, cylindrical tube that includes a flexible section 24. The conduit 12 has an internal cross-sectional diameter which is substantially constant to prevent flow disruptions and the existence of contaminates and/or air which can adversely affect the sample amount and integrity. In the embodiment shown in Figure 1 -4, the flexible section 24 is a piece of flexible tubing and the conduit 12 also includes a pair of remaining sections 26 and a pair of adapters 28 for connecting the flexible section 24 to the remaining sections 26.

The remaining sections 26 of the conduit 12 are typically tubes made of steel, stainless steel, aluminum, an elastomer, a polymer or any material that is not adversely effected by the fluid sample 14, the temperature and pressure in the conduit 12. In the embodiment shown in the Figures, the conduit 12 is designed for transporting a predetermined, relatively small amount of blood sample for the diagnostic system 22. Thus, an internal diameter 27 of the remaining sections 26 of about 0.01 -0.10 inches is sufficient to transport the blood sample. Alternatively, remaining sections 26 having a larger internal diameter 27 can be used if necessary.

Preferably, the flexible section 24 has a circular cross-sectional shape and has an internal diameter 29 similar to the remaining sections 26 of the conduit 12 to minimize flow disruptions in the conduit 12 which can adversely affect accuracy of the amount of fluid sample 14 being transferred. Thus, for the diagnostic system 22 described above, the flexible section 24 has an internal diameter 29 of between about 0.01 and 0.10 inches. Alternatively, the flexible section 24 can have an oval cross-sectional shape

since this shape typically expands easier than the circular cross-sectional shape when the flexible section 24 is subjected to an increase of pressure. However, the oval cross-sectional shape may disrupt flow of the fluid sample 14 in the conduit 12.

Typically, the flexible section 24 is thin walled, i.e., having a wall thickness 30 which is between about 8 to 1 2 thousandths of an inch to allow the flexible section 24 to expand with an increase of pressure in the conduit 12. As the wall thickness 30 of the flexible section 24 increases, additional pressure is needed to expand the flexible section 24 and the device

10 loses sensitivity to slight pressure increases. Alternatively, as the wall thickness 30 decreases, the flexible section 24 is subject to bursting. Typically, a wall thickness 30 of .008 inches for the flexible tubing is sufficient to prevent bursting since the expansion of the flexible tubing is contained by the substantially incompressible medium 18.

The flexible section 24 is made of an elastomer such as silicon or buna-n since elastomers deform relatively easily. A silicon tube purchased from Helix Medical, located in Carpenteria, CA makes an excellent flexible section 24. The term elastomer as used herein means a polymeric material which at room temperature can be stretched to at least twice its original length and upon immediate release of stress will return quickly to approximately its original length. Alternatively, the flexible section 24 can be made from a polymer such as polyvinyl chloride. However, polymers are typically less flexible than elastomers and additional pressure may be necessary to expand the polymer.

The flexible section 24 can be any length which allows the flexible section 24 to expand in the event of an increase in pressure in the conduit 12. In the embodiment shown in the Figures, the length of tubing is about three-quarters of an inch long to facilitate attachment of the flexible section 24 to the pair of adapters 28.

As previously mentioned, the adapters 28 connect the flexible section 24 to the pair of remaining sections 26. The adapters 28 can be designed in a number of alternate ways to connect the flexible section 24 to the pair of remaining sections 26. For example, with reference to Figures 1

- and 2, each adapter 28 is attached to the housing 16 and includes a substantially cylindrical body 32, a first end 34, an opposed second end 36, a seal surface 38, a cylindrical passageway 40, and an attachment flange 42. For ease of manufacturing, preferably, each adapter 28 is fabricated from a continuous piece of steel, stainless steel, aluminum or some other suitable material.

The first end 34 is suitable for attachment to the flexible section 24 and includes a tubular projection 44 which fits snugly inside the flexible section 24. An outer surface of the tubular projection 44 includes a circumferential, beveled surface 46 that retains the flexible section 24 to the adapter 28.

The second end 36 is suitable for attachment to the remaining section 26. In the embodiment shown in the Figures, the second end 36 includes an internally threaded surface 48 which accepts an externally threaded surface 50 of a flangeless ferrules fitting 52 such as that sold by Upchurch Scientific, located in Oak Harbor, WA. The ferrules fitting 52 adapts and seals the tubular remaining section 26 to the adapter 28.

As shown in Figures 1 and 2, the seal surface 38 is cylindrical and is disposed between the body 32 and the first end 34. The seal surface 38 is sized to receive an "O" ring seal 54 for sealing the connection between the adapter 28 and the housing 16.

The cylindrical passageway 40 connects the first end 34 and second end 36 in fluid communication. Preferably, the cylindrical passageway 40 has an internal diameter 27 similar to the flexible section 24 and the remaining section 26 to prevent disruption of the flow of the fluid sample 14. Thus, for the diagnostic system 22 described above, the cylindrical passageway 40 has an internal diameter 27 of between about .01 and 0.10 inches.

The attachment flange 42 is an outwardly extending circumferential ring attached to the body 32 proximate the second end 36 which is used to retain the adapter 28 to the housing 16. The attachment flange 42 includes a plurality of flange apertures 56 extending therethrough. Adapter bolts 58 extend through the flange apertures 56 to retain each adapter 28 to the housing 16.

The housing 16 includes an internal cavity 60 which substantially encloses at least a portion of the flexible section 24 and forms a substantially sealed internal chamber 62 around the portion of the flexible section 24. In the embodiment shown in the Figures, the internal cavity 60 encloses and seals the entire flexible section 24 and the housing 16 is substantially rectangular with opposed sides 64, a front surface 66, a back surface 68, a top surface 70 and a bottom surface 72. The housing 16 can be made of a number of alternate materials such as acrylic, steel, stainless steel or aluminum.

An adapter opening 74 having a circular cross-section extends through each of the opposed sides 64. Each adapter opening 74 is sized and shaped to receive one of the adapters 28. Each adapter opening 74 has a circumferential lip 78 for contacting the "0" ring seal 54 for sealing the adapter 28 to the housing 16. Each side 64 also includes a plurality internally threaded surfaces 76. Each internally threaded surface 76 is sized and shaped to receive one of the adapter bolts 58 to retain the adapter 28 to the housing 16.

The top surface 70 includes a sensor opening 80 which is in fluid communication with the internal chamber 62 for receiving the sensor 20. The shape and size of the sensor opening 80 varies according to the sensor 20. As shown in Figures 1 and 2, the sensor opening 80 can have a circular cross-section. The top surface 70 also includes a plurality of internally threaded surfaces (not shown) for receiving sensor bolts 84 for retaining the sensor 20 to the housing 16.

The housing 16 also includes a fill opening 86 which is in fluid communication with the internal chamber 62 for filling the chamber 62 with the incompressible medium 18 and a fill plug 88 for sealing the fill opening 86. In the embodiment shown in the Figures, the fill opening 86 and fill plug 88 are positioned in the back surface 68 and the fill opening 86 includes an internally positioned surface (not shown) and the fill plug 88 includes an externally threaded surface (not shown) which mates the internally threaded surface. The fill plug 88 also includes a hexagonal opening 89 for receiving a tool (not shown) for installing the fill plug 88.

The substantially incompressible medium 18 is disposed within and substantially fills the internal chamber 62 of the housing 16. The substantially incompressible medium 18 typically is a fluid such as deionized water. The deionized water can include 1 % of Tween 20 (available from Sigma Chemical, St. Louis, MO.) to decrease the tendency of air bubbles clinging on the internal cavity 60. Preferably, the fluid has a thermal coefficient of expansion which is less than about 0.3 x 10 ^"3 v/v/c° so that a change in temperature does not adversely effect the accuracy of the device 10.

To ensure that the internal chamber 62 is completely filled by the substantially incompressible medium 18, a water-filled internal chamber 62 can be placed in a vacuum oven (not shown) and subjected to a vacuum of about 25-35 inches of mercury at a temperature of about 40 -60 C. for about 10-20 minutes. Subsequently, the device 10 is removed from the vacuum oven and the fill plug 88 is installed while the device 10 is still hot.

The sensor 20 is in communication with the substantially incompressible medium 18. The sensor 20 detects a change of pressure of the substantially incompressible medium 18 in the internal chamber 62 which results from the change of pressure in the conduit 12. Typically, the sensor 20 is a pressure transducer such as The Nova PIX Series, sold by Lucas Novasensor 20 located at Fremont, CA. The sensor 20 includes a control wire 92 which electrically connects the sensor 20 to the diagnostic system 22.

Alternately, the sensor 20 can be a pressure gauge, a fixed- cistern barometer, a U-type absolute pressure gauge, a differential mercury barometer, a manometer well, a differential gauge, or a volumetric-seal gauge or any other pressure measuring device as detailed in Perry's Chemical

Engineers' Handbook.

As shown in Figs. 1 -3, a cylindrical-shaped retainer ring 88 is used to attach the sensor 20 to the housing 16. The retainer ring 88 can be made of steel, stainless steel or other suitable material. The retainer ring 88 includes a retainer flange 90 extending outwardly from the retainer ring 88. The retainer flange 90 includes a plurality of retainer openings (not shown) for receiving the sensor bolts 84 for attaching the retainer ring 88 to the sensor

^' 20. An "O" ring 94 fits into a circumferential groove 96 in the sensor 20 to seal the sensor 20 to the housing 16.

In operation, with reference to Fig. 4, the fluid sample 14 is withdrawn from a collection tube 98 through the probe 21 into the conduit

12. A flow restriction, i.e., a blood clot, in the fluid sample 14 results in a pressure decrease in the conduit 12 which causes the flexible section 24 to contract. The contraction of the flexible section 24 causes the pressure of the substantially incompressible medium 18 in the internal chamber 62 to decrease. The sensor 20 detects the decrease in pressure in the medium 18.

Thus, the sensor 20 is able to detect a change of pressure in the conduit 12.

The present invention provides a device 10 for detecting a change of pressure in the conduit 12 without the need for side connections in the conduit 12 which can contain contaminants or air which would adversely affect the integrity and the amount of the fluid sample 14 being transferred. Additionally, since the sensor 20 is in communication with the incompressible medium 18 instead of the fluid sample 14 being transported by the conduit 12, there is no chance of adverse reaction between the sensor 20 and the fluid sample 14.

Although the present invention is described in considerable detail with reference to certain preferred versions, other versions are possible. For example, the housing 16 might enclose only a portion of the flexible section 24 instead of the entire flexible section 24 as shown in the Figures or the flexible section 24 is made of rubber. Therefore, the spirit and scope of the appended claims should not be limited to the description of the preferred versions contained herein.