|Publication number||US6998273 B1|
|Application number||US 10/114,913|
|Publication date||Feb 14, 2006|
|Filing date||Apr 1, 2002|
|Priority date||Feb 9, 2000|
|Also published as||US7488606, US20050277202|
|Publication number||10114913, 114913, US 6998273 B1, US 6998273B1, US-B1-6998273, US6998273 B1, US6998273B1|
|Inventors||William H. Fleming, Timothy P. Hyatt, Dudley B. Thomas|
|Original Assignee||A-Fem Medical Corporation|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (42), Referenced by (33), Classifications (21), Legal Events (7)|
|External Links: USPTO, USPTO Assignment, Espacenet|
This application is a divisional of Ser. No. 09/501,339, filed Feb. 9, 2000 now U.S. Pat. No. 6,365,417.
This invention relates to assays, and particularly to lateral flow assays in which a liquid analyte is applied to a sample zone of a test strip, allowed to migrate along the strip by capillary action, and detected in a capture zone.
Assays are frequently used to detect the presence of analytes in aqueous test samples in clinical and forensic medicine, and for environmental testing, food contaminant testing, and drug use testing. There is a growing demand for such assays that are based on reactions between specifically reactive substances, and that can be conducted outside of the laboratory setting, for example at home.
There are a number of over-the-counter (“OTC”) home testing and health care professional (“HCP”) diagnostic devices that can be used to collect human body fluids and perform diagnostic assays. An example of such a diagnostic device is a dipstick used for midstream urine sampling, such as found in pregnancy testing, or testing of urine from a specimen placed in a receptacle. Both OTC and HCP diagnostic devices can be lateral flow devices, in which a liquid specimen is applied to a sample zone of a lateral flow chromatographic test strip. The strip is usually made of a porous carrier material (such as nitrocellulose) so that the liquid travels along the strip by capillary action to an indicator zone, which indicates a presence, absence, or quantity of the analyte. Sometimes a wick is attached to the strip to help move the liquid specimen into or along the sample zone. Numerous lateral flow analytical devices have been disclosed, and include those shown in U.S. Pat. Nos. 4,775,636; 4,703,017; 4,861,711; 4,855,240; 4,857,453; 4,943,522; 4,945,042; 4,496,654; 5,001,049; 5,075,078;5,126,241; 5,451,504; 5,424,193; 5,712,172; and WO92/12428; WO 94/01775; and WO 97/06439, each of which is incorporated by reference.
Many lateral flow devices are one-step lateral flow assays in which a biological fluid is placed in a sample area on a bibulous strip, and allowed to migrate along the strip until the liquid comes into contact with a specific binding partner that interacts with an analyte in the liquid. Once the analyte interacts with the binding partner, a signal (such as a fluorescent dye) indicates that the interaction has occurred. Multiple discrete binding partners can be placed on the strip (for example in parallel lines) to detect multiple analytes in the liquid. The test strips can also incorporate control indicators, which provide a signal that the test has adequately been performed, even if a positive signal indicating the presence (or absence) of an analyte is not seen on the strip.
Although lateral flow devices have been widely used in clinical practice, there are still obstacles to both clinical and home use because of the difficulty obtaining some specimens (such as blood), or the reluctance of users to collect certain specimens (such as urine). Even in situations in which urine tests are widely used (such as urine analysis for drug testing), it can be awkward or distasteful to obtain the specimens for analysis. Moreover, it is sometimes difficult to positively identify a specimen as coming from a particular individual, because of the possibility that specimens have been mislabeled or exchanged after collection but before testing.
U.S. Pat. No. 5,910,122 (D'Angelo) discloses a saliva collector which encases a tip of an aspirating pipette, for subsequent analysis in a separate test. U.S. Pat. No. 5,380,492 shows another saliva collector which incorporates an indicator in the collector that changes color when sufficient saliva has been collected. U.S. Pat. No. 4,635,488 is a body fluid sampling device which has an absorbent nib that collects saliva and conducts it to an analysis element in an interior of a tube. The analysis element can be placed in the tube after saliva collection is completed. Alternatively, liquid communication between the nib and analysis element is altered by a porous, absorbent but hydrophobic disc that conducts the saliva to the analysis element after being wetted with a wetting agent.
A problem that has retarded the more widespread use of intra-oral collection devices is that regulatory agencies and test subjects have been concerned about the reverse migration or reflux of detection reagents from the device into the mouth. Such reflux could cause a test subject to experience a noxious taste, or even carry potentially harmful detection reagents into the mouth of the subject.
Many lateral flow tests are used for regulatory or legal purposes, and proper identification of the test subject is important. Prior devices have included a label on which identifying information can be written (for example, in U.S. Pat. No. 5,380,492). However, incorrect information can be intentionally or unintentionally entered on such labels.
It would be advantageous to provide a simple and convenient assay that is suitable for home use, avoids reflux of test reagents, and/or which can readily identify a person from whom the biological specimen is obtained.
The present invention is a lateral flow device for analyzing analytes in a liquid, such as drug metabolites in saliva. In some of the disclosed embodiments, the lateral flow device includes a collection member which communicates with a lateral flow member that includes test result indicators which signal the presence, absence and/or quantity of analytes in a test liquid. The collection member absorbs or adsorbs a liquid (such as saliva in the mouth) to which the collection member is exposed. A removable barrier between the collection member and the lateral flow member inhibits the flow of liquid from the collection member when the removable barrier is present, but permits the liquid to flow into and through the lateral flow member when the barrier is removed. In some embodiments, a sufficiency indicator may be displayed by the collection member to indicate when a sufficient amount of saliva has been collected to remove the barrier.
In particularly disclosed examples, the barrier may be a negative barrier or a positive barrier. A positive barrier is a substantially liquid impermeable barrier, for example a substantially liquid impermeable plastic sheet. In some embodiments, the lateral flow member overlaps the collection member or abuts it in end to end contact, and the removable barrier may be a removable spacer interposed between the collection member and the lateral flow member. Alternatively, the liquid impermeable barrier may be a negative barrier, such as a gap between the collection member and the lateral flow member. Instead of removing such a barrier, the gap is closed, for example by sliding the collection member and the lateral flow member into contact with one another. In a particularly disclosed embodiment, the collection member and lateral flow member slide into an overlapping contiguous relationship.
The present device may be used for collecting oral secretions for subsequent analysis. A particularly suitable intra-oral device includes a housing that holds the lateral flow member and at least a portion of the collection member, with the collection member extending outside of the housing for placement in the mouth. The removable barrier may be contained within and accessible from outside of the housing, to permit the removable barrier to be removed from the between the collection member and lateral flow member when sufficient oral secretions (such as saliva) have been collected. The housing may define one or more windows though which the test result indicators can be viewed on the lateral flow member. It my be advantageous to close the windows, with clear or magnifying materials such as glass or plastic, to help isolate the interior of the housing from the oral environment.
The housing may also include slots through which a portion of the barrier extends to an exterior of the housing. An interior portion of the barrier is interposed between the collection member and the lateral flow member, so that the external portion of the barrier may be grasped and pulled out of the housing to permit the collection member and lateral flow member to come into contiguous liquid transferring contact. Alternatively, when the barrier is a negative (e.g. gap) barrier, a sliding member may move either or both of the collection member and lateral flow member into overlapping or other contiguous contact.
When the housing is intended for insertion into a body orifice (such as the mouth), it is particularly advantageous for an anterior portion of the housing to taper toward the collection member to be more comfortably retained in the orifice. Hence when the collection member extends anteriorly out of the housing, the housing tapers in that same direction to facilitate insertion of the device into the liquid collection orifice (such as the mouth). In some embodiments, the housing also has substantially flat top and bottom surfaces, and a low profile, to fit comfortably between the dentition of a test subject.
In other embodiments, multiple lateral flow members can be used instead of a single such member. For example, two lateral flow members may be opposed back to back, in communication with a single oral collection member. A removable substantially liquid impermeable positive or negative barrier may be present between the collection member and both of the lateral flow members. Removal of the barriers allows test liquid to flow from the collection member into both of the lateral flow devices. When the lateral flow members are opposed back to back, the test results of both strips can easily be read in situ (without removal from any housing) by viewing opposite faces of the housing. However, more than two lateral flow members can be arranged in a variety of configurations, for example in a triangular or quadrilateral array.
A physical identifier region may be present on the device to interact with and identify the user. The physical identifier region may be a segregated fingerprint receiving region, such as a relatively smooth, segregated area on the housing at a position that a digit (such as a thumb) of a test subject would grasp the housing to insert it in the mouth.
In a more particular embodiment, the device includes an elongated housing having dimensions that allow the housing to be placed in a mouth of a subject. A lateral flow chromatography member is contained within the housing, and a collection member is positioned to contact the lateral flow chromatography member. The collection member is elongated and extends to outside of the housing for insertion and retention in the mouth of a subject, and a removable barrier is present between the collection member and the lateral flow chromatography member, to interrupt movement of liquid between the collection member and the lateral flow chromatography member when the barrier is in place. The collection member and the lateral flow chromatography member are both elongated and longitudinally overlap, and are spaced from one another by the removable barrier, which is substantially impervious to any liquid, regardless of the chemical characteristics of the liquid.
The housing defines an access opening though which the removable barrier is accessible for removal. The barrier is a liquid impervious sheet that extends between the collection member and the lateral flow chromatography member along a region of overlap between the collection member and the lateral flow chromatography member. An external portion of the barrier material extends through the access opening in the housing, to the exterior of the housing, so that the external portion can be grasped outside of the housing and pulled out of the housing to remove it. Once the barrier has been removed, the collection member and lateral flow member become contiguous. A bias member, such as a resilient pad, may bias at least one of the collection member or the lateral flow member into contact with one another, to improve contiguous contact between them after the barrier is removed. A window in the housing allows a test result indicator to be viewed without removing the lateral flow chromatography member from the housing.
To help assure that an adequate amount of liquid has been collected by the device before the barrier is removed, a soluble sample adequacy indicator (such as a dye) may be present on the lateral flow member. The indicator is solubilized by the collected liquid, and migrates along the collection member with liquid collected by the collection member. This flow moves the sufficiency indicator to a pre-selected position on the collection member, so that the sufficiency indicator can be viewed through a window in the housing once the pre-selected amount of liquid has been collected by the collection member. The housing may also include a liquid port through which substances can be introduced through the housing on to the lateral flow member and/or the collection member.
Any of the embodiments of the device may also include a wicking member in contact with the lateral flow chromatography member. The wicking member may be positioned to draw liquid from the collection member through the lateral flow member. For example, the wicking member may be a highly absorbent material contiguous with the lateral flow member, at a proximal and/or distal region of the liquid flow path from the mouth through the lateral flow member.
Particular embodiments of the lateral flow member include one or more analyte indicator agents that interact with an analyte in the liquid to provide a test result (such as a color change in an indicator line). Many different indicator agents may be used, such as a capture agent which captures an analyte. The capture agents may be a binding partner, such as an antibody, for example a monoclonal or polyclonal antibody. The indicator agents may be arranged in a series of indicator lines which detect different analytes. The indicator agent may provide an optical, electrical, or magnetic signal to indicate a presence of an analyte in the liquid.
The disclosed device therefore provides a two-step lateral flow device, in which the first step is collection of liquid into the collection member, and the second step is elimination of the barrier. The device can be used in a method of performing an analysis on a body fluid, by placing the collection member of the device in contact with a body fluid, allowing the collection member to collect the body fluid, and removing the barrier from between the collection member and the lateral flow member. In particular applications, the method is designed to collect oral secretions, such as saliva, by placing the device in the mouth of a test subject. In those embodiments in which a liquid sufficiency indicator is included, the barrier is not removed until the sufficiency indicator provides a signal that adequate liquid has been collected to perform the test. Once the liquid flows into the lateral flow member, a signal from the indicator(s) allows the presence, absence, and/or quantity of the analyte to be detected. In particular embodiments of the method, the test subject grasps the housing with a digit (such as the thumb) on a fingerprint receiving region of the housing, for subsequent positive identification of the test subject.
The disclosed embodiments also include a kit for detection of an analyte in a liquid, such as an oral liquid. The kit includes the collection device, and instructions for placing the device in a liquid collection cavity (such as the mouth), waiting until the collection member collects oral liquid, then removing the removable barrier.
The foregoing summary will be better understood by reference to the drawings, and the following detailed description.
Although many different embodiments of the invention are possible, several particular examples are disclosed in this detailed description. These examples (like the foregoing summary of the embodiments) are meant to facilitate understanding of the claimed invention, and are not intended to limit the claims to particularly disclosed or summarized embodiments.
The following definitions and methods are provided to better define the present invention and to guide those of ordinary skill in the art in the practice of the present invention.
Analyte: a compound (e.g. drug, hormone, antigen, antibody, hapten, lectin, apoprotein, cofactor) to be measured. Examples of analytes are a drug, hormone, antigen, antibody, hapten, lectin, apoprotein, or cofactor. More specific examples are drug metabolites, for example cotinine as a marker of nicotine use, or a hormone such as human chorionic gonadotropin (HCG) as a marker of pregnancy.
Antibody: an immunoglobulin having an area on its surface or in a cavity that specifically binds to and is thereby defined as complementary with a particular spatial and polar organization of another molecule, such as a protein. The antibody may be polyclonal or monoclonal. Antibodies may include a complete immunoglobulin or fragments thereof, which immunoglobulins include different classes and isotypes, such as IgA, (IgA1 and IgA2), IgD, IgE, IgM and IgG (IgG1, IgG2, IgG3 and IgG4) etc. Fragments thereof may include Fab, Fv and F(ab′)2, Fab′ and the like. Antibodies include chimeric antibodies made by recombinant methods.
Antigen: Any compound capable of binding with an antibody, or against which antibodies can be raised.
Binding partner: Any molecule or composition capable of recognizing and binding to a specific structural aspect of another molecule or composition. Examples of such binding partners and corresponding molecule or composition include antigen/antibody, hapten/antibody, lectin/carbohydrate, apoprotein/cofactor and biotin/streptavidin.
Comprising: Including at least.
Label: Any molecule or composition bound to an analyte, analyte, analog or binding partner that produces a signal, for example a signal detectable by visual, spectroscopic, photochemical, biochemical, immunochemical, electrical, optical or chemical means. Examples of labels include enzymes (such as horseradish peroxidase or alkaline phosphatase); radiolabels (e.g. tritiated hydrogen, or radioactive iodine, carbon or phosphorus); colloidal gold particles; colored latex particles (U.S. Pat. Nos. 4,275,149; 4,313,734; 4,373,932; 4,954,452); magnetic beads (such as DYNABEADS); and fluorescent dyes (e.g. fluorescein and rhodamine).
Lateral Flow Device: Devices that include bibulous or non-bibulous matrices capable of transporting analytes and reagents to a pre-selected site. Many such devices are known, in which the strips are made of nitrocellulose, paper, cellulose, and other bibulous materials. Non-bibulous materials can be used, and rendered bibulous by applying a surfactant to the material.
Lateral flow chromatography strip: A test strip used in lateral flow chromatography, in which a test sample suspected of containing an analyte flows (for example by capillary action) through the strip (which is frequently made of materials such as paper or nitrocellulose). The test fluid and any suspended analyte can flow along the strip to a detection zone in which the analyte (if present) interacts with a detection agent to indicate a presence, absence and/or quantity of the analyte.
Liquid impermeable: Having a physical structure that substantially prevents passage of any liquid through. For example, the liquid will not pass through even if the chemical characteristics of a barrier are changed (for example, even if a hydrophobic barrier is changed to a hydrophilic barrier by chemical treatment). Liquid impermeable barriers are often characterized by a structure that is not porous, or has pores that are too small to substantially allow any significant amounts of liquid to flow through them.
Positive/direct reporting: refers to an increase in the reporting or detection signal with increasing analyte concentration.
Specific binding agent: An agent that binds substantially only to a defined target. The determination that a particular agent binds substantially only to a protein may readily be made by using or adapting routine procedures. One suitable in vitro assay makes use of the Western blotting procedure (described in many standard texts, including Antibodies: A Laboratory Manual by Harlow and Lane).
As used in this specification, the singular includes the plural, unless the context clearly indicates otherwise. Hence “a” and “the” include the plural, unless otherwise indicated.
Housing 22 has an anterior tip 38 (
A longitudinal recessed channel 60 (
Chromatography strip 24, which is seated in housing 22, is seen in isolation in
Capture agents (such as specific binding partners, for example monoclonal antibodies) are aligned as indicator lines 92, 94, 96, 98, 100 (
When strip 24 is seated in housing 22, support 90 is seated on the bottom of housing 22, within the channel 60 (
In operation, device 20 (with barrier sheet 70 wrapped around the housing as in
Once the indicator signal is observed, device 20 may be removed from the mouth, and the external portion of sheet 70 peeled away from housing 22 (to the position shown in phantom lines in
Liquid then moves from wick 84 into and through lateral flow member 86 by capillary action. As the liquid encounters the capture agents in indicator lines 92–100, the capture agents undergo a physical and/or chemical transformation, that can be detected visually, or by a sensor 110. This transformation can indicate the presence, absence, and/or quantity of an analyte in the liquid. Continued distal flow of liquid distally through strip 24 is encouraged by distal wick 88, which absorbs and draws liquid toward it. Wick 88 also acts as a reservoir for collecting the liquid.
Once the test has been performed, device 20 can be discarded or recycled for reuse.
Another embodiment is shown in
This embodiment differs from
Another embodiment of the invention is shown in
A sliding ramp 338 (shown in isolation in
In use, ramp 338 is placed in the channel, with tab 345 protruding through the bottom slot to the exterior of the housing. In this position, ramp 338 can be manipulated (by pushing tab 345 forward and backward) between a retracted position (
The front of strip 24 (supported by ledge 347) is slightly lower than the main body of the strip supported by channel surface 60, and there is a gap 360 of about 1.00 to 1.50 mm between distal collection member 80 and the top surface of proximal wick 84. However, when ramp 338 is pushed to the extended position (
With ramp 338 in the retracted position of
Housing 22 is provided with a first electrical contact 401 along one edge of window 44, and a series of adjacent metallic electrical contacts 402, 404, 406, 408 and 410 through housing 22 along an opposing edge of window 44. Each of the contacts 402–410 corresponds to a respective one of indicator lines 92–100, and is connected to a transverse edge of its respective indicator line by a conductor, such as an electrically conductive wire 412, 414, 416, 418 or 420. An opposing transverse edge of each indicator line is connected to a conductor, such as wires 422, 424, 426, 428 or 430 which all lead to conductor 401. An electrical circuit (not shown) can be used to establish an electrical potential across contact 401 to contacts 402–410, so that an electrical current can flow between contact 401 and one or more of contacts 402–410 when one or more of indicator lines 92–100 becomes electrically conductive.
When the indicator line is intended to provide a signal about the presence, absence, and/or quantity of an analyte in the liquid, the electrical conductivity of the indicator line changes. The change in electrical conductivity can be detected by a flow of electrical current through a respective contact 402–410. For example, if indicator lines 94 and 98 capture an analyte, the electrical conductivity of the line changes, such that an electrical current flows from contact 401, through wires 424 and 428, indicator lines 94, 98, wires 414, 418, and contacts 404, 408. The flow of electrical current through contacts 404, 408 can be detected by a current flow meter, to measure a positive reaction. The level of current detected can also be used as an indicator of the positivity of the reaction.
Yet another embodiment of the invention is shown in
Strip 524 includes an elongated absorbent or adsorbent collector strip 550 having parallel planar top and bottom faces, with an indicator dye 552 a, 552 b localized on the opposing faces of the strip. A distal end of strip 524 is sandwiched between a pair of anterior wicking strips 554 a, 554 b. The distance between strips 554 a, 554 b widens in a distal direction, so that their inner faces receive between them a pair of lateral flow members 556 a, 556 b which are mounted on and extend partially the length of a rigid plastic support 558. Lateral flow members 556 a, 556 b are laminated or otherwise adhered to opposing faces of support 558, and extend along support 558 at least the distance of windows 544 a, 544 b. The distal ends of lateral flow members 556 a, 556 b are sandwiched between and adhered to the ends of a pair of posterior wicking strips 560 a, 560 b, which are laminated or otherwise adhered distally to the top and bottom surfaces of support 558, and sandwich the lateral flow members 556 a, 556 b therebetween.
The lateral flow members 556 a, 556 b each include a plurality of indicator lines on their outer faces (not shown, but similar to those in
In other embodiments (not illustrated), more than two lateral flow members could be used, for example four such members, with a surface of each of the different lateral flow members facing through a different test window of a multi-sided or cylindrical housing 522.
In an alternative embodiment (not illustrated), collection strip 550 may be coplanar with but spaced from a wicking element and lateral flow member. Instead of separate barrier sheets, an absorbent member can be placed between the collection strip and wicking elements to establish a flow path from the collection member to the lateral flow member.
When used with housing 522, strip 524 is placed in housing 522 with collector strip 550 extending proximally from, and retained in position by, nose 540 of housing 522. A pair of resilient, compressed, top and bottom pads 568 a, 568 b are respectively provided between anterior wicks 554 a, 554 b and the top 526 and bottom 528 of housing 522, to help secure strip 524 in a neutral position between the top and bottom of the housing. Pads 568 a, 568 b may be made of a liquid impermeable material, or of an absorbent material that expands when moistened. A central portion of strip 524 can also be held in a neutral position (half way between the top and bottom of the housing) by peripheral lips 547 a, 547 b of windows 544 a, 544 b.
In use, collection strip 550 can be placed in the mouth where it collects liquid at least until indicator dyes 552 a, 552 b are solubilized by the collected liquid and migrate to a position at which they can be viewed through indicator windows 546 a and 546 b. Barrier sheets 560 a, 560 b are then removed from housing 522, so that liquid flow is permitted to occur in a distal flow direction toward and through lateral flow members 556 a, 556 b. The indicator agents in the indicator lines on the lateral flow members then indicate the presence, absence, and/or quantity of a number of different analytes in the liquid.
Certain embodiments of the device may also be provided with an identifier, such as an identifier that interacts physically with a user to uniquely identify the test subject. An example of such an identifier is shown in
The fingerprint could be used to positively identify the person from whom the specimen was taken. This may be important, for example, if the test is performed to detect drugs of abuse in an employee or prison inmate, or indicators of disease in a person undergoing an insurance physical. The fingerprint identification is particularly useful in legal or other administrative proceedings, in which the identity of the test subject may be at issue.
Other physical identifiers that substantially uniquely identify the test subject could also be used. For example a dried blood or saliva drop on an absorbent pad, would provide a sample for DNA identification.
Although the collector member was shown as an elongated strip of constant width and thickness in earlier illustrated embodiments, the collector member (like many other aspects of the invention) can take quite different forms. Two variations in the shape of the collector member are shown in
The preferred embodiment of the device is injection molded using white polypropylene plastic (as shown in
The device is molded in two pieces, an upper piece and a lower piece, with interlocking tabs along the long sides to hold the two pieces together in the correct relationship. The posterior ends of the device are shaped (rounded) to present an attractive appearance. All other surfaces are chamfered to eliminate all sharp edges, with a chamfer radius of about 0.015625 inch. The upper and lower piece together cooperatively define therebetween a slot for the oral collection device in the anterior tip with sufficient dimension (height and width) so as not to interfere with the sample flow from the oral collector to the proximal wick (e.g. 84 in
The device includes a sufficiency indicator window (46 in
The lower piece has a longitudinal channel molded into it to hold the test strip. The width of this channel is 5 mm+0.5 mm. This channel has positioning ribs along its length that are 1 mm, +0.0 mm, −0.5 mm in height above the base of the channel, and are 2¾ inch long and with the center point 1⅞ inch from the anterior end. The height of the channel from the bottom of the lower piece to the top of the bottom of the channel is designed to bring the proximal wick up to the upper edge of the lower piece. The lower piece also has a positioning pin (e.g. 103 in
There is a void in the lower piece extending from the distal end of the rigid plastic support (e.g. 90 in
Having illustrated and described the principles of the invention in several embodiments, it should be apparent to one skilled in the art that the invention can be modified in arrangement and detail without departing from such principles. We claim all modifications coming within the spirit and scope of the following claims.
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|U.S. Classification||436/514, 435/970, 436/528, 435/287.1, 435/7.94, 435/805, 435/810, 435/287.2, 436/541, 436/810, 435/7.1, 436/518, 422/412|
|International Classification||G01N33/558, G01N33/53|
|Cooperative Classification||Y10S435/805, Y10S435/97, Y10S435/81, Y10S436/81, G01N33/558|
|Apr 19, 2005||AS||Assignment|
Owner name: A-FEM MEDICAL CORPORATION, OREGON
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:FLEMING, WILLAM H.;HYATT, TIMOTHY P.;THOMAS, DUDLEY B.;REEL/FRAME:016106/0727
Effective date: 20000509
|Jan 8, 2008||AS||Assignment|
Owner name: QUANTRX BIOMEDICAL CORPORATION, OREGON
Free format text: CHANGE OF NAME;ASSIGNOR:A-FEM MEDICAL CORPORATION;REEL/FRAME:020325/0781
Effective date: 20051202
|Jan 31, 2008||AS||Assignment|
Owner name: PLATINUM LONG TERM GROWTH VII, LLC, NEW YORK
Free format text: SECURITY AGREEMENT;ASSIGNOR:QUANTRX BIOMEDICAL CORPORATION;REEL/FRAME:020442/0576
Effective date: 20080123
|Aug 11, 2009||FPAY||Fee payment|
Year of fee payment: 4
|Sep 27, 2013||REMI||Maintenance fee reminder mailed|
|Feb 11, 2014||FPAY||Fee payment|
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|Feb 11, 2014||SULP||Surcharge for late payment|
Year of fee payment: 7