Patent Application
20160184743
A portion of the disclosure of this patent document may contain material which is subject to copyright protection. The copyright owner has no objection to the facsimile reproduction by anyone of the patent disclosure, as it appears in the Patent and Trademark Office patent files or records, but otherwise reserves all copyright rights whatsoever.
The present invention relates generally to the field of measurements of biological liquid samples. Specifically, the present invention relates to a pipette tip that permits the liquid sample to be filtered so as to remove debris and particulates that might disrupt the measurement.
Many applications in the field of analytical research and clinical testing utilize methods for analyzing liquid samples. Among those methods are optical measurements that measure absorbance, turbidity, fluorescence/luminescence, and optical scattering measurements. Optical laser scattering is one of the most sensitive methods, but its implementation can be very challenging, especially when analyzing biological samples in which suspended particles are relatively transparent in the medium.
One particle that often requires evaluation within a liquid is bacteria. The presence of bacteria is often checked with biological liquids, such as urine, amniotic, pleural, peritoneal and spinal liquids. In a common analytical method, culturing of the bacteria can be time-consuming and involve the use of bacterial-growth plates placed within incubators. Normally, laboratory results take several days to determine whether the subject liquid is infected with bacteria.
In some optical measurement systems, cuvettes have been used to receive liquid samples that are then subjected to the optical measurement by transmission of an input beam through the cuvette and observation of the forward scatter signals. These devices have been used relative to the detection of bacteria within the liquid. To optically measure the bacteria, it is often necessary to filter the fluid from other particles. In use, the cuvette is often filled by a pipette assembly that contains the liquid sample. However, filtering the fluid sample prior to transfer to the cuvette or within the cuvette can often be difficult.
Some clinical and research activities involve testing of large numbers of samples, and a variety of semi-standardized air displacement pipetting devices have been developed to simplify transfer of samples between containers while avoiding contamination. These generally involve pulling some volume of air from a disposable pipette tip using a manually actuated cylinder, and pulling liquid into the tip by the vacuum created, and then releasing the sample by moving the cylinder back to the original position, venting the tip to ambient pressure, or by applying an overpressure by use of the same cylinder.
Filtration is used to remove particles of a range of sizes from liquids, and for some medical and lab activities it is common to use a syringe and syringe filter device, which are commonly available. In this arrangement the liquid is drawn into the syringe volume, a filter is attached to the syringe luer fitting, and then the sample is pressed through the filter. This activity requires the assembly of the filter on the syringe after the syringe has been loaded with the sample and thereby exposed to the sample, which might include pathogenic organisms, and is therefore prone to unintended spills, drips, or cross-contamination. Additionally, since the syringe plunger is directly contacting the incompressible sample liquid, it is possible to apply extremely high pressure to the sample, which can crack the filter body leading to spills.
Accordingly, there is a need for an improved pipette assembly with an integrated filter to permit the fluid sample to be easily pulled into the pipette and filtered prior to dispensing the fluid sample.
The present invention is a pipette-filtration assembly having a main body defining a central channel, an outer channel, a first valve, and a second valve. The first valve is associated with the central channel and permits flow in a first direction while substantially hindering flow in a second direction. The second valve is associated with the outer channel and permits flow in the second direction while substantially hindering flow in the first direction. At least one filter is used to filter a fluid sample as the fluid sample flows in the first direction and/or the second direction.
In a further aspect, the present invention is a pipette-filtration assembly having a main body, a filter mount located within the main body defining a bypass channel and a main channel, a first valve, and a second valve. The first valve is associated with the bypass channel and permits flow in a first direction while substantially hindering flow in a second direction. The second valve is associated with the main channel and a filter and permits flow in the second direction while substantially hindering flow in the first direction. At least one filter is used to filter a fluid sample as the fluid sample flows in the first direction and/or the second direction. The first direction is generally a substantially upward direction with respect to the main body while the second direction is generally a substantially downward direction with respect to the main body.
In another aspect, the present invention is a disposable pipette tip with one or two stages of integral filtration, primarily for use with an air-displacement pipetting or transfer system. This is a low-cost and compact device that can be a replacement for standard pipette tips, but where the liquid being transferred is filtered as it is drawn into the body of the pipette tip, or filtered as it is released from the pipette tip, or filtered in both directions. A two-channel flow check valve is incorporated to divert flow and ensure that filtration is in one-direction only, and that materials filtered during the intake stroke are not merely flushed back into the liquid during release.
Additional aspects of the invention will be apparent to those of ordinary skill in the art in view of the detailed description of various embodiments, which is made with reference to the drawings, a brief description of which is provided below.
While the invention is susceptible to various modifications and alternative forms, specific embodiments will be shown by way of example in the drawings and will be described in detail herein. It should be understood, however, that the invention is not intended to be limited to the particular forms disclosed. Rather, the invention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention as defined by the appended claims.
The drawings will herein be described in detail with the understanding that the present disclosure is to be considered as an exemplification of the principles of the invention and is not intended to limit the broad aspect of the invention to the embodiments illustrated. For purposes of the present detailed description, the singular includes the plural and vice versa (unless specifically disclaimed); the words “and” and “or” shall be both conjunctive and disjunctive; the word “all” means “any and all”; the word “any” means “any and all”; and the word “including” means “including without limitation.”
The lower tip 12 is a tapered hollow tube with a small aperture at the bottom through which samples can be drawn or released. It is desirable to filter the vast majority of the fluid that is transferred to the pipette-filtration assembly and to minimize the amount of fluid that is not filtered. As such it is advantageous to minimize the enclosed volume in lower tip 12, as this volume may not be fully filtered during the filtering process as described below. The minimum volume of the lower tip 12 may be less than about five percent of the filtered fluid volume, and is generally not more than about ten percent of the transferred fluid volume.
The lower portion of the filter portion 16 is divided into a central inner channel allowing for in-flow of a sample into the upper chamber 14, and an annular outer channel allowing for out-flow from the upper chamber 14. The central inner channel and the annular outer channel are divided from each other by a vertical tubular wall 18.
A flexible membrane 20 is used to restrict flow in one direction, while permitting the flow in the opposing direction. In the illustrated embodiment, the flexible membrane 20 is sandwiched between an upper part (including vertical tubular wall 18) and a lower part of the filter portion 16. The upper side of the filter portion 16 surrounding the inner and outer channels is fitted with a sealing lip 21 around the circumference. The flexible membrane 20 (e.g., a thin rubber or resilient membrane) is fixed to the upper portion of the dividing tube wall 18 between the inner and outer channels at the same position in the filter portion 16 such that a peripheral portion 22 of the membrane 20 contacts and forms a seal on the lip 21 of the outer channel. A pressure on the membrane 20 in one direction will deflect the peripheral portion 22 of the membrane 20 downwardly away from the lip 21 to permit flow from the upper chamber 14, and pressure on the opposite side will force the peripheral portion 22 of the membrane 20 against the sealing lip 21, substantially inhibiting flow into the upper chamber 14. In operation, the fluid sample flows (as shown by arrow 36) around the peripheral portion 22 of the membrane 20 downwardly towards lower wall 26, which includes openings 28 (
The membrane 20 can extend across the inner channel tube, and have a slit or a plurality of partial slits or cuts to form one or more deflectable flaps 24. The inner channel is also fitted with a sealing ledge or lip 25 on one side (at the opposite side of the outer channel as sealing lip 21) such that flow in one direction flexes the flap 24 away from the lip 25 to permit flow (as shown by arrow 38), and pressure in the opposite direction forces the membrane 20 against the lip 25 to seal the channel and substantially inhibit flow.
Either or both of inner central or annular outer channels may be fitted with a porous filter 30 such as a glass, plastic, or paper fiber mat, foam, or porous membrane. The filter(s) 30 can be of one or more porosities. Further, the filter(s) 30 could be impregnated with chemo-effectors for modifying the chemistry of the sample, or detection such as colorimetric or luminescent detection, dye, or the addition of drugs, antibodies, nanoparticles, or any other additions to the sample. As shown, the fluid (which is drawn upwardly into the upper chamber 14 via the lower tip 12 and the deflected flap 24) flows downwardly from the upper chamber 14 through the filter 30 and through openings 32 (
The configuration described in
By the above description, one check-valve membrane 20 will permit inflow of fluid to the upper chamber 14 via the opening defined by the flap 24, and the other valve membrane 20 permits discharge of fluid from the upper chamber 14, with capability to include as many as four stages of filtration in the process.
In another version of this device, a valve membrane can be loose in a chamber with a lip on one side, but free to move in the axis of flow to open. In another alternative, there could be two separate membranes—one annular membrane for the outer valve, and an independent element for an inner valve. Additionally, either the inner or outer valve membrane could be staked and flex as is shown in
A filter mount 116 is located within the transition region 113. The filter mount 116 has shaped lower surface features that allow it to be properly orientated and registered within the transition region 113, which has an asymmetric shape for receiving the filter mount 116. The filter mount 116 may include outwardly-projecting ribs or inwardly-defined depressions that are able to interact with corresponding features on the main body 111 to assist in locking the filter mount 116 in its proper location within the main body 111. The filter mount 116 is configured such that a bypass channel (see fluid flow arrow in
The pipette-filtration assembly 110 also includes a check-valve membrane 120 and a filter 130. The check-valve membrane 120 may be located on the side of the filter mount 116 nearest the lower tip 112 and covers the main channel and the bypass channel. The check-valve membrane 120 is flexible yet resilient, such that it is able to flex or deform and then return to its prior shape. It may be composed of a thin rubber or any other suitable material. The check-valve membrane 120 is used to restrict flow in a first direction while permitting flow in a second direction. For example, the check-valve membrane 120 allows fluid to flow through the bypass channel into the upper chamber 114 while at the same time preventing fluid from flowing through the main channel into the upper chamber 114. Similarly, the check-valve membrane 120 allows fluid to flow through the main channel and out of the lower tip 112 while preventing fluid from flowing out of the bypass channel out of the lower tip 112. The first direction is generally a substantially upward direction with respect to the main body 111 and toward the pipette, while the second direction is generally a substantially downward direction with respect to the main body 111 and toward a lower portion of the main body 111. However, the first direction, the second direction, or both the first direction and the second direction may be oriented at an angle relative to the main body 111.
A portion of the main body 111 in the transition region 113 includes a bypass sealing lip 122. A first peripheral portion 126 of the check-valve membrane 120 contacts and forms a seal with the bypass sealing lip 122. The first peripheral portion 126 is able to flex towards and away from the bypass sealing lip 122 to thereby define a first valve. A portion of the filter mount 116 that encompasses the main channel includes a main sealing lip 124 around its perimeter. A second peripheral portion 128 of the check-valve membrane 120 contacts and forms a seal with the main sealing lip 124. The second peripheral portion 128 is able to flex towards and away from the main sealing lip 124 to thereby define a second valve. The first valve is able to permit fluid to flow upwards through the bypass channel while substantially inhibiting the fluid from flowing downwards through the bypass channel, which is discussed in more detail below relative to
The filter 130 may be located on the opposite side of the filter mount 116, towards the upper chamber 114. The filter 130 can be captured mechanically in its location to prevent flow around the filter 130, or can be welded, adhered, staked, or otherwise secured to the structure of the filter mount 116 or the upper chamber 114. The filter mount 116 may include an upwardly-projecting rib 119 that can be utilized to secure the filter 130. Additionally or alternatively, either or both of the bypass channel or main channel may be fitted with one or more additional porous filters such as a glass, plastic, or paper fiber mat, foam, or porous membrane. If more than one filter is used within the pipette-filtration assembly 110, the different filters can be of one or more porosities. Further, the filters could be impregnated with chemo-effectors for modifying the chemistry of the sample, or detection such as colorimetric or luminescent detection, dye, or the addition of drugs, antibodies, nanoparticles, or any other additions to the sample.
The configuration illustrated in
In summary,
The fluid sample is drawn by pressure into the lower tip 112 and deflects the first peripheral portion 126 of the check-valve membrane 120 away from the bypass sealing lip 122 and through the bypass channel into the upper chamber 114 of the main body 111. Venting or applying pressure to the upper chamber 114 of the main body 111 reverses the flow in the bypass channel and forces the check-valve membrane 120 to return to the bypass sealing lip 122, effectively stopping reverse flow through the bypass channel. The fluid sample flows from the upper chamber of the main body 111 through a porous filter 130 and deflects the second peripheral portion 128 of the check-valve membrane 120 away from the sealing lip 14 on the filter mount 116 permitting free flow of now-filtered sample into the lower tip 112 and out of the pipette-filtration assembly 110.
In
In
Each of these embodiments and obvious variations thereof is contemplated as falling within the spirit and scope of the claimed invention, which is set forth in the following claims. Moreover, the present concepts expressly include any and all combinations and subcombinations of the preceding elements and aspects.
This application claims the benefit of U.S. Provisional Application No. 62/098,166, filed Dec. 30, 2014, which is hereby incorporated by reference herein in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 62098166 | Dec 2014 | US |
