Patent Description:
Blood sampling is a common health care procedure involving the withdrawal of at least a drop of blood from a patient. Blood samples are commonly taken from hospitalized, homecare, and emergency room patients either by finger stick, heel stick, or venipuncture. Blood samples may also be taken from patients by venous or arterial lines. Once collected, blood samples may be analyzed to obtain medically useful information including chemical composition, hematology, or coagulation, for example.

Blood tests determine the physiological and biochemical states of the patient, such as disease, mineral content, drug effectiveness, and organ function. Blood tests may be performed in a clinical laboratory or at the point-of-care near the patient. One example of point-of-care blood testing is the routine testing of a patient's blood glucose levels which involves the extraction of blood via a finger stick and the mechanical collection of blood into a diagnostic cartridge. Thereafter, the diagnostic cartridge analyzes the blood sample and provides the clinician a reading of the patient's blood glucose level. Other devices are available which analyze blood gas electrolyte levels, lithium levels, and ionized calcium levels. Some other point-of-care devices identify markers for acute coronary syndrome (ACS) and deep vein thrombosis/pulmonary embolism (DVT/PE).

Blood samples contain a cellular portion, blood cells, and a plasma portion, blood plasma. Core lab tests comprise the bulk of blood testing, and use centrifugation to separate blood plasma from blood cells for analysis in a lab before the tubes are presented to large diagnostic instruments. Centrifugation is the commonly accepted process for plasma separation for general use across many laboratory tests. Centrifugation typically takes <NUM> to <NUM> minutes and involves heavy labor or complex work flow.

In a point-of-care environment, blood samples are presented to the instrument at or near the patient bedside. Most point-of-care tests use whole blood samples that are transferred from a blood collection tube by pipette or syringe, because plasma samples are not available at the patient's bedside.

A biological fluid separation device having the features defined within the preamble of claim <NUM>, is described in <CIT>.

The present invention provides a biological fluid separation device as defined by the features of claim <NUM> that allows for efficient separation of plasma from a blood sample. A biological fluid separation device of the present disclosure is adapted to receive a blood sample having a cellular portion or cells and a plasma portion or plasma. A biological fluid separation device of the present disclosure separates plasma from cells using a track-etched membrane and cross-flow filtration.

In one embodiment, a biological fluid separation device of the present disclosure provides a plasma separation device integrated within an evacuated blood collection tube. Advantageously, a biological fluid separation device of the present disclosure provides for the immediate separation of plasma during clinical blood draws and the ability for controlled dispense of the separated plasma sample to a point-of-care cartridge or other diagnostic instrument port or testing device. A biological fluid separation device of the present disclosure provides a blood collection workflow that is no different than a conventional blood collection workflow using vacuum tubes such as the BD Vacutainer® and corresponding venous access sets. A biological fluid separation device of the present disclosure generates plasma that is immediately available for controlled dispense to a diagnostic instrument at the point-of-care or in a near-patient diagnostic setup.

A biological fluid separation device of the present disclosure allows for immediate plasma separation during the blood draw therefore eliminating the need for a separate centrifugation process and also allows controlled plasma sample transfer to a diagnostic port using the embedded precise drop dispenser of the present disclosure. A biological fluid separation device of the present disclosure eliminates the need for conventional blood collection tubes to be centrifuged, which often requires being sent to the lab for centrifugation.

In accordance with an embodiment of the present disclosure, a biological fluid separation device is adapted to receive a blood sample having a first portion and a second portion. The biological fluid separation device includes a housing having an inlet and an outlet and a venting plug, and a blood chamber having a blood chamber inlet and a blood chamber outlet, with the blood chamber adapted to receive the blood sample. The biological fluid separation device further includes a separated chamber having a chamber outlet, and a separator disposed between the blood chamber and the separated chamber, with the separator adapted to trap the first portion in the blood chamber and allow the second portion to pass through the separator into the separated chamber. The biological fluid separation device further includes an outer housing removably connectable to the housing, wherein the outer housing contains a first vacuum and the housing contains a second vacuum, and with the housing connected to the outer housing, the housing is disposed within the outer housing. The first vacuum and the second vacuum are in communication via the venting plug.

In one configuration, the first portion is a cellular portion, and the second portion is a plasma portion. The first vacuum and the second vacuum may draw the blood sample within the housing and draw the plasma portion through the separator into the separated chamber.

In certain configurations, the separator may include a membrane surface having pores. Optionally, the separator is a track-etched membrane.

The biological fluid separation device may also include a closure covering the inlet, and, with the housing connected to the outer housing, the closure may seal the open end of the housing. The inlet of the housing may be provide at a first end and the outlet of the housing may be provided at an opposite second end.

In other configurations, the biological fluid separation device may also include a plasma collection channel between the chamber outlet and the outlet of the housing. Optionally, the plasma collection channel may have a serpentine shape.

In still other configurations, the biological fluid separation device may further include a dispenser assembly which includes a cap covering the outlet and including the venting plug which allows air to pass therethrough and prevents the second portion of the blood sample from passing therethrough. The dispenser assembly may also include a deformable portion transitionable between an initial position in which the second portion is contained within the separated chamber and a deformed position in which a portion of the second portion is expelled from the separated chamber. With the cap removed from the outlet, and the deformable portion transitioned to the deformed position, a portion of the second portion may expelled from the biological fluid separation device.

In still further configurations, the biological fluid separation device may include a diagnostic assembly which includes a diagnostic interface in communication with the chamber outlet of the separated chamber, and a sensor for testing the second portion.

In accordance with another embodiment of the present disclosure a biological fluid separation device adapted to receive a blood sample having a cellular portion and a plasma portion, may include an inner housing having an inlet and an outlet. The biological fluid separation device may also include a blood chamber having a blood chamber inlet and a blood chamber outlet, wherein the blood chamber receives the blood sample, and a plasma chamber having a plasma chamber outlet. The biological fluid separation device may also include a separator disposed between the blood chamber and the plasma chamber, with the separator adapted to trap the cellular portion in the blood chamber and allow the plasma portion to pass through the separator into the plasma chamber, and an outer housing removably connectable to the inner housing. With the inner housing connected to the outer housing, the inner housing may be disposed within the outer housing, and wherein a vacuum is defined by at least one of the inner housing and the outer housing to draw the plasma portion of the blood sample through the separator.

The biological fluid separation device may further include a biological fluid separation device connector removably connectable to a connector of a blood collection tube. Optionally, the outer housing of the biological fluid separation device may include an evacuated tube.

In accordance with still another embodiment of the present disclosure, a biological fluid separation device may be adapted to receive a blood sample having a cellular portion and a plasma portion. The biological fluid separation device may include an outer housing having an open end, a closed end, and a sidewall extending therebetween and defining an interior. The biological fluid separation device may further include a dispenser unit removably connectable to the outer housing, and an inner housing within the outer housing. The inner housing may include a blood chamber having a blood chamber inlet and a blood chamber outlet, the blood chamber configured to receive the blood sample and the blood chamber outlet in fluid communication with a portion of the interior of the outer housing. The biological fluid separation device further including a plasma chamber having a plasma chamber outlet, and a separator disposed between the blood chamber and the plasma chamber. The separator may be adapted to trap the cellular portion in the blood chamber and allow the plasma portion to pass through the separator into the plasma chamber. The biological fluid separation device further including a plasma collection channel extending from the plasma chamber outlet into the dispenser unit.

Optionally, the biological fluid separation device may also include a stopper sized relative to the interior of the outer housing to provide sealing engagement with the sidewall of the outer housing. The stopper may divide the interior of the outer housing into a first sealed portion and a second portion. In certain configurations, with the dispenser unit disconnected from the outer housing, the plasma portion is contained within the dispenser unit.

Corresponding reference characters indicate corresponding parts throughout the several views. The exemplifications set out herein illustrate exemplary embodiments of the disclosure, and such exemplifications are not to be construed as limiting the scope of the disclosure in any manner.

However, it is to be understood that the invention may assume alternative variations and step sequences, except where expressly specified to the contrary. It is also to be understood that the specific devices and processes illustrated in the attached drawings, and described in the following specification, are simply exemplary embodiments of the invention.

<FIG> illustrate an exemplary embodiment of a biological fluid separation device of the present disclosure. Referring to <FIG>, a biological fluid separation device <NUM> of the present disclosure is adapted to receive a blood sample <NUM> having a first portion, such as a cellular portion <NUM> and a second portion, such as a plasma portion <NUM>. The present disclosure provides a biological fluid separation device and a separation process that allows for efficient separation of plasma from a blood sample.

In one embodiment, a biological fluid separation device of the present disclosure provides a plasma separation device integrated within an evacuated blood collection tube. Advantageously, a biological fluid separation device of the present disclosure provides for the immediate separation of plasma during clinical blood draws and the ability for controlled dispense of the separated plasma sample to a point of care cartridge or other diagnostic instrument port or testing device. A biological fluid separation device of the present disclosure provides a blood collection workflow that is no different than a conventional blood collection workflow using vacuum tubes such as the BD Vacutainer® and corresponding venous access sets. A biological fluid separation device of the present disclosure generates plasma that is immediately available for controlled dispense to a diagnostic instrument at the point of care or in a near-patient diagnostic setup.

Referring to <FIG>, in one exemplary embodiment, a biological fluid separation device <NUM> generally includes an inner housing or internal tube <NUM>, an outer housing or external tube <NUM>, and a separator <NUM>.

Referring to <FIG>, the inner housing <NUM> includes an inlet <NUM>, an outlet <NUM>, a blood chamber <NUM> that receives the blood sample <NUM>, a separated chamber, such as a plasma chamber <NUM>, and the separator <NUM>. In one embodiment, the inlet <NUM> of the inner housing <NUM> is at a first end and the outlet <NUM> of the inner housing <NUM> is at an opposite second end. In other embodiments, the configuration of the inlet <NUM> and the outlet <NUM> may be varied for different applications.

Referring to <FIG>, the blood chamber <NUM> receives the blood sample <NUM> and includes a blood chamber inlet <NUM>, a blood chamber outlet <NUM>, and a blood chamber channel <NUM> running between the blood chamber inlet <NUM> and the blood chamber outlet <NUM>. In one embodiment, the blood chamber inlet <NUM> is in fluid communication with the inlet <NUM> of the biological fluid separation device <NUM>. In one embodiment, the blood chamber <NUM> also includes a blood discard chamber <NUM> that is in fluid communication with the blood chamber outlet <NUM>. In this manner, the cellular portion <NUM> of the blood sample <NUM> can be moved and stored within the blood discard chamber <NUM> after flowing through the blood chamber channel <NUM> and past the separator <NUM>. The plasma chamber <NUM> includes a plasma chamber outlet <NUM>.

Referring to <FIG>, the separator <NUM> is disposed between the blood chamber <NUM> and the plasma chamber <NUM>. In one embodiment, the separator <NUM> is adapted to trap the cellular portion <NUM> of the blood sample <NUM> in the blood chamber <NUM> and allow the plasma portion <NUM> of the blood sample <NUM> to pass through the separator <NUM> into the plasma chamber <NUM>.

In one embodiment, the separator <NUM> includes a membrane surface <NUM> having pores or filter holes <NUM>. The membrane surface <NUM> has a first or blood side <NUM> and a second or plasma side <NUM>. Referring to <FIG>, the blood chamber channel <NUM> is parallel to the membrane surface <NUM> as discussed in more detail below.

In one embodiment, the separator <NUM> comprises a track-etched membrane. The biological fluid separation device <NUM> of the present disclosure separates plasma <NUM> from cells <NUM> using a track-etched membrane and cross-flow filtration. A track-etched membrane of the biological fluid separation device <NUM> is a filter with pores small enough to prevent the flow of red blood cells or cells but permit the flow of plasma therethrough. Plasma flow through the membrane is driven by a pressure across the membrane, i.e., a transmembrane pressure, but this flow also brings cells to the membrane surface and risks membrane clogging. This is prevented by continuous blood flow parallel to the membrane surface, i.e., cross-flow filtration, which flushes cells away and allows continuous plasma filtration.

In one embodiment, the biological fluid separation device <NUM> of the present disclosure controls the blood flow rate on one side, i.e., a first or blood side <NUM>, of a track-etched membrane while the differential pressure across the track-etched membrane extracts plasma <NUM> to the other side, i.e., a second or plasma side <NUM>, of the track-etched membrane, as shown in <FIG>. A blood sample <NUM> that falls into the blood chamber <NUM> flows within the blood chamber channel <NUM> parallel to the membrane surface <NUM> of the separator <NUM>. In this manner, such parallel flow keeps cells <NUM> of the blood sample <NUM> from clogging the pores <NUM> of the separator <NUM>, whose submicron pores <NUM> allow the flow of plasma <NUM> to other side, i.e., the plasma side <NUM>, and further out into the plasma chamber <NUM>.

In one embodiment, the separator <NUM> comprises a track-etched membrane with submicron holes <NUM> to filter plasma <NUM> from a blood sample <NUM> that is continuously flowing parallel to the membrane surface <NUM>. In this manner, clogging of the filter holes <NUM> is prevented, as shown in <FIG>. Advantageously, the separation process of the present disclosure does not continuously trap the cells inside the filter structure, eventually reducing the yield to zero.

A biological fluid separation device <NUM> of the present disclosure is designed to effectively separate blood cells from the plasma without damaging the cells, e.g., cell rupture known as hemolysis. A biological fluid separation device <NUM> of the present disclosure balances fundamental blood flow characteristics in a way to maximize the plasma yield within a given time while preserving the cell integrity. In some embodiments, a biological fluid separation device <NUM> of the present disclosure is designed using mathematically modeling, e.g., using an equivalent electric circuit method, each portion of the filtration system to determine critical flow and geometric parameters that will maximize yield, minimize separation time, and minimize hemolysis.

In one embodiment, the separator <NUM> comprises a less than <NUM> microns thick track-etched membrane. In one embodiment, the separator <NUM> comprises a <NUM> - <NUM> micron thick track-etched membrane. In another embodiment, the separator <NUM> comprises a <NUM> - <NUM> micron thick track-etched membrane.

In one embodiment, the submicron holes <NUM> of the track-etched membrane are approximately <NUM> - <NUM> microns in diameter. In another embodiment, the submicron holes <NUM> of the track-etched membrane are approximately <NUM> - <NUM> microns in diameter.

In one embodiment, the active filter surface area of the track-etched membrane is less than <NUM><NUM>. Advantageously, this allows the separator <NUM> of the present disclosure to fit inside of conventional blood collection tubes and also generate high quality plasma with minimal analyte bias, and especially low bias of cardiac markers such as Troponin and BNP.

Referring to <FIG>, in one embodiment, the separator <NUM>, the blood chamber <NUM>, and the plasma chamber <NUM> form a separator chip <NUM>. In one embodiment, the separator chip <NUM> is sized to be contained within the inner housing <NUM>.

In one embodiment, the separator chip <NUM> has a chip length of approximately <NUM> - <NUM>. In one embodiment, the separator chip <NUM> has a chip width of approximately <NUM> - <NUM>. In one embodiment, the separator chip <NUM> has a chip thickness of approximately <NUM> - <NUM>.

In one embodiment, the height of the blood chamber <NUM> is approximately <NUM> - <NUM> microns. In one embodiment, the length of the blood chamber <NUM> is approximately <NUM> - <NUM> microns. In one embodiment, the height of the plasma chamber <NUM> is approximately <NUM> - <NUM> microns.

In one embodiment, the biological fluid separation device <NUM> of the present disclosure includes an outer housing <NUM> that is removably connectable to the inner housing <NUM>. Referring to <FIG>, with the inner housing <NUM> connected to the outer housing <NUM>, the inner housing <NUM> is disposed within the outer housing <NUM>. The outer housing <NUM> includes an open end <NUM>, a closed end <NUM>, and a sidewall <NUM> extending therebetween and defining an interior <NUM>. In one embodiment, the outer housing <NUM> contains a first vacuum <NUM>.

Referring to <FIG>, in one embodiment, the biological fluid separation device <NUM> includes a closure <NUM> that covers the inlet <NUM>. Referring to <FIG>, the closure <NUM> is engaged with the inlet <NUM> to seal the biological fluid separation device <NUM>. The closure <NUM> protectively covers the inlet <NUM>. The closure <NUM> allows for introduction of a blood sample <NUM> into the blood chamber <NUM> of the inner housing <NUM> and may include a pierceable self-sealing stopper <NUM> with an outer shield <NUM> such as a Hemogard™ cap commercially available from Becton, Dickinson and Company. In one embodiment, the closure <NUM> includes a stopper adapter <NUM>.

Referring to <FIG>, in one embodiment, the outer housing <NUM> is removably connectable to the inner housing <NUM> via the closure <NUM>. For example, the closure <NUM> secures to the outer housing <NUM>. In this manner, with the inner housing <NUM> connected to the outer housing <NUM>, the closure <NUM> seals the open end <NUM> of the outer housing <NUM>.

In one embodiment, the outer housing <NUM> is an evacuated tube. In one embodiment, the outer housing <NUM> may be a vacuum containing blood collection tube such as a Vacutainer® blood collection tube commercially available from Becton, Dickinson and Company.

Referring to <FIG>, in the context of the claimed invention, the inner housing <NUM> includes a cap <NUM> that is removably attachable to the outlet <NUM> and that protectively covers the outlet <NUM>. In the context of the claimed invention, the cap <NUM> includes a venting plug <NUM> which allows air to pass therethrough and prevents the plasma <NUM> of the sample <NUM> from passing therethrough.

The construction of the cap <NUM> and venting plug <NUM> allows air to pass through the cap <NUM> while preventing the plasma <NUM> of the blood sample <NUM> from passing through the cap <NUM> and may include a hydrophobic filter. The venting plug <NUM> has selected air passing resistance that may be used to finely control the filling rate of the blood chamber <NUM> and/or the plasma chamber <NUM> of the inner housing <NUM>. By varying the porosity of the plug <NUM>, the velocity of the air flow out of the cap <NUM>, and thus the velocity of the blood sample flow into the inner housing <NUM>, may be controlled.

Referring to <FIG>, in one embodiment, the outer housing <NUM> contains a first vacuum <NUM> and the inner housing <NUM> contains a second vacuum <NUM>. In one embodiment, the first vacuum <NUM> and the second vacuum <NUM> are in communication via the venting plug <NUM>. In other embodiments, the inner housing <NUM> may also include a second venting plug and/or a venting plug valve <NUM> that allow the first vacuum <NUM> and the second vacuum <NUM> to be in communication theretogether.

The first vacuum <NUM> and the second vacuum <NUM> draw a blood sample <NUM> within the inner housing <NUM> and draw the plasma portion <NUM> through the separator <NUM> into the plasma chamber <NUM>, as described in more detail below.

In one embodiment, the venting plug <NUM> of the cap <NUM>, which allows air to pass therethrough and prevents the plasma <NUM> of the sample <NUM> from passing therethrough, seals the plasma chamber <NUM> once plasma <NUM> wets out the venting plug <NUM> and ends separation.

Referring to <FIG>, in one embodiment, the inner housing <NUM> of the biological fluid separation device <NUM> includes a dispenser assembly or dispenser unit <NUM> that allows the plasma <NUM> contained within a plasma collection channel <NUM> to be expelled in a precise, controlled, and efficient manner.

Referring to <FIG>, in one embodiment, the inner housing <NUM> includes a plasma collection channel <NUM> between the plasma chamber outlet <NUM> and the outlet <NUM> of the inner housing <NUM>. In this manner, after separation, the plasma <NUM> flows through the plasma chamber outlet <NUM> to the plasma collection channel <NUM>. The plasma collection channel <NUM> allows the plasma <NUM> to be collected and stored within the inner housing <NUM>, until it is desired to transfer the plasma <NUM> out of the inner housing <NUM>.

In one embodiment, the plasma collection channel <NUM> has a serpentine shape. The diameter of the serpentine shape of the plasma collection channel <NUM> is sized to prevent bubbles from forming within the plasma <NUM> and to keep the plasma <NUM> flowing through the channel <NUM> in capillary form. The serpentine shape of the plasma collection channel <NUM> also allows for the length of the channel that the plasma <NUM> flows into to be increased while maintaining capillary form.

Referring to <FIG>, in one embodiment, the inner housing <NUM> also includes a dispenser assembly or dispenser unit <NUM> that allows the plasma <NUM> contained within the plasma collection channel <NUM> to be expelled in a precise, controlled, and efficient manner. For example, once a sufficient amount of plasma <NUM> is collected within the plasma collection channel <NUM>, the inner housing <NUM> can be removed from the outer housing <NUM>, as shown in <FIG>. Next, the cap <NUM> is removed from the outlet <NUM>, and the dispenser assembly <NUM> is used to dispense the plasma <NUM> from the plasma collection channel <NUM> of the inner housing <NUM>, as shown in <FIG>.

The dispenser assembly <NUM> of the inner housing <NUM> can include any dispenser structure that allows the plasma <NUM> to be expelled from the plasma collection channel <NUM> of the inner housing <NUM> in a precise, controlled, and efficient manner.

Referring to <FIG> and <FIG>, one exemplary embodiment of the dispenser assembly <NUM> will be described. In one embodiment, the dispenser assembly <NUM> includes the plasma collection channel <NUM>, the cap <NUM>, the venting plug <NUM>, a deformable portion <NUM>, an air vent <NUM>, and a one-way valve <NUM>. In one embodiment, the deformable portion <NUM> includes a first dispenser bulb <NUM> and a second dispenser bulb <NUM>.

In one embodiment, the cap <NUM> covers the outlet <NUM> and includes the venting plug <NUM> which allows air to pass therethrough and prevents the plasma portion <NUM> of the blood sample <NUM> from passing therethrough.

In one embodiment, the deformable portion <NUM> is transitionable between an initial position in which the plasma portion <NUM> is contained within the plasma collection channel <NUM> and a deformed position in which a portion of the plasma portion <NUM> is expelled from the plasma collection channel <NUM>. Referring to <FIG>, with the cap <NUM> removed from the outlet <NUM>, and the deformable portion <NUM> transitioned to the deformed position, a portion of the plasma portion <NUM> is expelled from the biological fluid separation device <NUM>, i.e., the plasma collection channel <NUM> of the inner housing <NUM>. In one embodiment, the deformable portion <NUM> includes a first dispenser bulb <NUM> and a second dispenser bulb <NUM>.

In use, when the deformable portion <NUM> is squeezed, air is pushed in the inner housing <NUM> to expel the plasma <NUM> out the plasma collection channel <NUM>. In one embodiment, when the deformable portion <NUM> is squeezed, the air vent <NUM> on the deformable portion <NUM> is covered by a finger of a user to force air through one-way valve <NUM> to expel the plasma <NUM> out the plasma collection channel <NUM>.

When the deformable portion <NUM> is released, the air vent <NUM> is no longer covered and air inflates the deformable portion <NUM> back up. Importantly, when the deformable portion <NUM> is released, the one-way valve <NUM> prevents plasma <NUM> from being pulled back into the plasma collection channel <NUM> after dispensing. In this manner, the dispensing assembly <NUM> of the present disclosure makes sure that the plasma <NUM> contained within the plasma collection channel <NUM> is only able to flow in one direction, i.e., out the plasma collection channel <NUM>.

Referring to <FIG>, in another exemplary embodiment, the plasma chamber outlet <NUM> of the inner housing <NUM> is in fluid communication with a portion of the interior <NUM> of the outer housing <NUM>. In such an embodiment, the dispensing assembly <NUM> of the inner housing <NUM> of the embodiment discussed with reference to <FIG> is removed, and plasma <NUM> is allowed to flow directly out the plasma chamber outlet <NUM> into a portion of the interior <NUM> of the outer housing <NUM>.

Referring to <FIG>, in this embodiment, as a blood sample <NUM> is drawn within the inner housing <NUM>, the plasma <NUM> is separated and exits the plasma chamber outlet <NUM> and collects in the outer housing <NUM>. Referring to <FIG>, the discard cellular portion <NUM> of the blood sample <NUM> remains within the inner housing <NUM> and can be disposed of after separation of the plasma <NUM>. Referring to <FIG>, the plasma <NUM> contained within the outer housing <NUM> may then be manually transferred or presented directly to clinical analyzers.

In operation, plasma generation in the embodiment shown in <FIG>, having a plasma collection unit or dispensing assembly <NUM> that allows for collection of the plasma <NUM> within the inner housing <NUM>, is stopped when the inner housing <NUM> is filled.

The blood draw and plasma volume varies from patient to patient as more or less blood is required to fill the plasma collection unit. Removal of the plasma collection unit in the embodiment shown in <FIG> allows additional plasma to be generated beyond the capacity of the collection unit. This gives the benefit of increased plasma volume (<NUM>-<NUM>µL from <NUM> whole blood depending on patient hematocrit, versus, e.g., <NUM>-<NUM>µL as may be limited by a plasma collection unit). Another benefit of the embodiment shown in <FIG> is that the plasma <NUM> sample can be presented directly to clinical analyzers or manually dispensed as dictated by workflow needs.

In the embodiment shown in <FIG>, the blood draw volume may increase to a flat <NUM> for all patients rather than varying between patients. Therefore, plasma separation time can increase in proportion with the increased blood draw volume. To mitigate the effect of increased run time, the embodiment shown in <FIG> can be combined with the off-patient separation method, as shown in <FIG>, as described in more detail below.

Referring to <FIG>, in another exemplary embodiment, the plasma chamber outlet <NUM> of the inner housing <NUM> is in fluid communication with a diagnostic assembly <NUM>. In such an embodiment, the dispensing assembly <NUM> of the inner housing <NUM> of the embodiment discussed with reference to <FIG> is removed, and plasma <NUM> is allowed to flow directly out the plasma chamber outlet <NUM> into the diagnostic assembly <NUM>. In such an embodiment, the plasma <NUM> fills the diagnostic assembly <NUM> for immediately testing of the plasma <NUM> for analytes after separation, without a need to dispense any plasma <NUM> from the biological fluid separation device <NUM>.

In one embodiment, the diagnostic assembly <NUM> includes a diagnostic interface <NUM> in communication with the plasma chamber outlet <NUM>, a sensor <NUM> for testing the plasma portion <NUM> of the blood sample <NUM>, and a venting plug <NUM> which allows air to pass therethrough and prevents the plasma portion <NUM> of the blood sample <NUM> from passing therethrough.

Referring to <FIG>, in one embodiment, the diagnostic assembly <NUM> includes a single sensor <NUM>. Referring to <FIG>, in one embodiment, the diagnostic assembly <NUM> includes three sensors <NUM>. Referring to <FIG>, in one embodiment, the diagnostic assembly <NUM> includes many sensors <NUM>. The diagnostic assembly <NUM> may include any number of sensors <NUM> needed for a desired testing application.

In one embodiment, the venting plug <NUM> of the diagnostic assembly <NUM> allows a vacuum to pull plasma <NUM> into the diagnostic interface <NUM> and to fill the diagnostic assembly <NUM>. For example, the venting plug <NUM> allows a vacuum <NUM> of the outer housing <NUM> to be in communication with the diagnostic assembly <NUM> to pull plasma <NUM> into the diagnostic assembly <NUM>. The venting plug <NUM> allows air to pass through while preventing the plasma <NUM> of the blood sample <NUM> from passing through. For example, once the plasma <NUM> fills the diagnostic assembly <NUM>, the venting plug <NUM> becomes saturated with blood and is wetted out. Once this happens, the diagnostic assembly <NUM> is filled with plasma <NUM> and no more plasma <NUM> is pulled into the diagnostic assembly <NUM>. With the diagnostic assembly <NUM> fully filled with plasma <NUM> and the venting plug <NUM> wetted out, the diagnostic assembly <NUM> is also sealed.

Referring to <FIG>, the diagnostic assembly <NUM> provides an on-board diagnostic unit for immediately testing the plasma <NUM> for analytes after separation. The diagnostic assembly <NUM> would utilize but not be limited to optical tests and other methods. The possible applications include qualitative "yes or no" tests for the presence of analytes, e.g., similar to common pregnancy tests, and quantitative results for analytes like cholesterol or sodium. Referring to <FIG>, in one embodiment, the on-board diagnostic assembly <NUM> could work alone. Referring to <FIG>, in one embodiment, the on-board diagnostic assembly <NUM> could interface with a test reader, for example, a diagnostic adapter <NUM>, e.g., a cell phone adapter, which connects the device <NUM> to a point of care diagnostic instrument <NUM>, e.g., a cell phone camera, for imaging and analysis of the sample results.

The diagnostic assembly <NUM> of the device <NUM> provides for efficient point-of-care workflow and clinician safety by eliminating the need to transfer the plasma <NUM> to a separate test cartridge. The diagnostic assembly <NUM> of the device <NUM> would also reduce the required volume of plasma <NUM> needed, e.g., in some embodiments, from ranges of <NUM>-<NUM> uL of plasma down to <NUM>-<NUM> uL, which would also reduce the run time of the device, e.g., in some embodiments, from <NUM>-<NUM> seconds down to <NUM>-<NUM> seconds, and required blood volume, e.g., in some embodiments, from <NUM>-<NUM> down to <NUM>-<NUM>.

Referring to <FIG>, use of a biological fluid separation device <NUM> of the present disclosure will now be described. Advantageously, a biological fluid separation device <NUM> of the present disclosure allows for a variety of different ways to collect and separate a plasma portion of a blood sample. For example, in one embodiment, a biological fluid separation device <NUM> of the present disclosure can be used with a conventional tube holder <NUM> having a cannula or non-patient needle <NUM> in a direct draw process as described in more detail below. In another embodiment, a biological fluid separation device <NUM> of the present disclosure can be used with a separate blood collection tube <NUM> in an indirect draw process as described in more detail below.

Referring to <FIG>, and <FIG>, use of a biological fluid separation device <NUM> of the present disclosure with a conventional tube holder <NUM> having a cannula or non-patient needle <NUM> in a direct draw process will now be discussed. A biological fluid separation device <NUM> of the present disclosure is compatible with conventional blood collection sets, e.g., a tube holder <NUM> or other conventional blood collection devices.

In use, a needle cannula or non-patient needle <NUM> (<FIG> and <FIG>) is inserted directly into the blood chamber <NUM> of the inner housing <NUM> of the biological fluid separation device <NUM> through the pierceable self-sealing stopper <NUM> of closure <NUM>. As shown in <FIG>, the biological fluid separation device <NUM> including the combined inner housing <NUM> and the outer housing <NUM> may be inserted into a conventional tube holder <NUM> having a cannula or non-patient needle <NUM> through which biological fluid, such as a blood sample <NUM>, is passed.

Next, with the biological fluid separation device <NUM> of the present disclosure directly connected with the tube holder <NUM>, a blood sample <NUM> is pulled into the blood chamber <NUM> of the inner housing <NUM> of the biological fluid separation device <NUM> from the conventional tube holder <NUM> by the draw of the first vacuum <NUM> contained in the outer housing <NUM> and the second vacuum <NUM> contained in the inner housing <NUM>. For example, when the non-patient needle <NUM> of the tube holder <NUM> pierces the stopper <NUM> of the closure <NUM>, the first vacuum <NUM> contained in the outer housing <NUM> and the second vacuum <NUM> contained in the inner housing <NUM> draw the blood sample <NUM> within the blood chamber <NUM> of the inner housing <NUM> via the non-patient needle <NUM> of the tube holder <NUM>.

The venting plug <NUM> and/or the venting plug valve <NUM> allow air to pass through while preventing the blood sample <NUM> and/or plasma portion <NUM> from passing through. Once the blood sample <NUM> fills the separator chip <NUM>, the first vacuum <NUM> and the second vacuum <NUM> are no longer in communication and begin acting separately. The second vacuum <NUM> continues discarding the cellular portion <NUM> of the blood sample <NUM> from the blood chamber outlet <NUM> to the blood discard chamber <NUM>. Furthermore, the first vacuum <NUM> continues drawing the plasma portion <NUM> through the separator <NUM> into the plasma chamber <NUM>. Once the plasma portion <NUM> fills the plasma chamber <NUM> and reaches the venting plug <NUM> the venting plug will become saturated with blood and wetted out, ending separation. If the desired operation requires it, the first vacuum <NUM> and second vacuum <NUM> can be connected by a venting plug valve <NUM> which allows air to pass between the first vacuum <NUM> and second vacuum <NUM> but prevents blood sample <NUM> from reaching the outer housing <NUM>.

Thus, in one embodiment, the first vacuum <NUM> and the second vacuum <NUM> initially act together as a single vacuum while the first vacuum <NUM> and the second vacuum <NUM> are in communication theretogether. Next, after the separator chip <NUM> is filled with blood sample <NUM>, the first vacuum <NUM> and the second vacuum <NUM> are no longer in communication together and act separately. In another embodiment, the first vacuum <NUM> and second vacuum <NUM> are kept in communication for the duration of operation by a venting plug valve <NUM>.

Once the blood sample <NUM> is collected and a desired amount of plasma <NUM> is separated, the biological fluid separation device <NUM> is removed from the tube holder <NUM>. Next, the separated plasma <NUM> is ready to be dispensed and/or analyzed as described in further detail below.

Referring to <FIG>, use of a biological fluid separation device <NUM> of the present disclosure with a separate blood collection tube <NUM> in an indirect draw process will now be discussed.

The indirect draw process allows for off-patient separation of plasma. Referring to <FIG>, in this embodiment, a blood sample <NUM> is collected in a conventional blood collection tube <NUM> in a conventional blood collection procedure. Blood collection using a conventional blood collection tube <NUM> allows a blood sample <NUM> to be collected from a patient faster. In this manner, the time that a patient is required to go through a blood collection procedure is reduced.

Next, referring to <FIG>, the blood collection tube <NUM> containing a blood sample <NUM> is then connected to the biological fluid separation device <NUM> for separation of the plasma <NUM> of the blood sample <NUM>. In this manner, separation of the plasma <NUM> using the biological fluid separation device <NUM> occurs while no blood collection devices are connected to a patient.

Referring to <FIG>, in one embodiment, the biological fluid separation device <NUM> includes a biological fluid separation device connector <NUM> removably connectable to a connector <NUM> of a blood collection tube <NUM>. This connection provides a sealed, secure connection between the biological fluid separation device <NUM> and the blood collection tube <NUM> during separation of plasma <NUM> using the biological fluid separation device <NUM>.

In one embodiment, the blood collection tube <NUM> includes an air vent <NUM>. The air vent <NUM> allows for air to be released to allow a vacuum within the biological fluid separation device <NUM> to pull the blood sample <NUM> into the biological fluid separation device <NUM> and draw the plasma portion <NUM> through the separator <NUM> into the plasma chamber <NUM>.

Once a desired amount of plasma <NUM> is separated, the biological fluid separation device <NUM> is removed from the blood collection tube <NUM>. Next, the separated plasma <NUM> is ready to be dispensed and/or analyzed as described in further detail below.

With the separated plasma <NUM> collected in the biological fluid separation device <NUM>, the separated plasma <NUM> is ready to be dispensed and/or analyzed. In one embodiment, the dispenser assembly <NUM> of the biological fluid separation device <NUM> may be used. For example, referring to <FIG>, in one embodiment, the inner housing <NUM> of the biological fluid separation device <NUM> includes a dispenser assembly or dispenser unit <NUM> that allows the plasma <NUM> contained within a plasma collection channel <NUM> to be expelled in a precise, controlled, and efficient manner.

Referring to <FIG>, in such an embodiment, once plasma separation and collection is complete, the inner housing <NUM> is separated from the outer housing <NUM> (<FIG>). In one embodiment, the inner housing <NUM> is separated from the outer housing <NUM> by removing the closure <NUM>, which is still attached to the inner housing <NUM>, from the outer housing <NUM>. Removal of the closure <NUM> may be accomplished by the user grasping both the outer shield <NUM> of the closure <NUM> and the outer housing <NUM> and pulling or twisting them in opposite directions.

Once the inner housing <NUM> is separated from the outer housing <NUM>, the cap <NUM> may then be removed from the inner housing <NUM> exposing the outlet <NUM> of the inner housing <NUM>. Removal may be accomplished by the user grasping an exterior portion of the cap <NUM> and pulling the cap <NUM> from the inner housing <NUM>. In one embodiment, the plasma <NUM> is held within the plasma collection channel <NUM> of the inner housing <NUM> by capillary action after removal of the cap <NUM>.

Referring to <FIG>, <FIG>, and <FIG>, the plasma <NUM> may then be dispensed from the plasma collection channel <NUM> of the inner housing <NUM> by activation of a dispensing assembly <NUM>. As described above, in one embodiment, the inner housing <NUM> also includes a dispenser assembly <NUM> that allows the plasma <NUM> contained within the plasma collection channel <NUM> to be expelled in a precise, controlled, and efficient manner. For example, referring to <FIG>, once a sufficient amount of plasma <NUM> is collected within the plasma collection channel <NUM>, the inner housing <NUM> can be removed from the outer housing <NUM>. Next, the cap <NUM> is removed from the outlet <NUM>, and the dispenser assembly <NUM> is used to dispense the plasma <NUM> from the plasma collection channel <NUM> of the inner housing <NUM>.

Referring to <FIG>, in one embodiment, the plasma <NUM> may be transferred to a sample container <NUM>, while minimizing the exposure of the medical practitioner to the plasma <NUM> of the blood sample <NUM>.

Referring to <FIG>, in one embodiment, the plasma <NUM> may be transferred to a device intended to analyze the plasma <NUM>, e.g., such as a point-of-care testing device <NUM>, a cartridge tester, or a near patient testing device, while minimizing the exposure of the medical practitioner to the plasma <NUM> of the blood sample <NUM>.

After plasma <NUM> separation, the separated plasma <NUM> is ready to be dispensed and/or analyzed. In one embodiment, the embodiment of the biological fluid separation device <NUM> shown in <FIG> may be used. For example, referring to <FIG>, in another embodiment, the plasma chamber outlet <NUM> of the inner housing <NUM> is in fluid communication with a portion of the interior <NUM> of the outer housing <NUM>. In such an embodiment, the dispensing assembly <NUM> of the inner housing <NUM> of the embodiment discussed with reference to <FIG> is removed, and plasma <NUM> is allowed to flow directly out the plasma chamber outlet <NUM> into a portion of the interior <NUM> of the outer housing <NUM>.

Referring to <FIG>, in such an embodiment, once plasma separation and collection is complete, the inner housing <NUM> is separated from the outer housing <NUM>. Referring to <FIG>, the discard cellular portion <NUM> of the blood sample <NUM> remains within the inner housing <NUM> and can be disposed of after separation of the plasma <NUM>. Referring to <FIG>, the plasma <NUM> contained within the outer housing <NUM> may then be manually transferred or presented directly to clinical analyzers.

In one embodiment, the separated plasma <NUM> fills a diagnostic assembly <NUM> for immediate testing of the plasma <NUM> for analytes after separation, without a need to dispense any plasma <NUM> from the biological fluid separation device <NUM>. For example, referring to <FIG>, the diagnostic assembly <NUM> provides an on-board diagnostic unit for immediately testing the plasma <NUM> for analytes after separation. The diagnostic assembly <NUM> would utilize but not be limited to optical tests and other methods. The possible applications include qualitative "yes or no" tests for the presence of analytes, e.g., similar to common pregnancy tests, and quantitative results for analytes like cholesterol or sodium. Referring to <FIG>, in one embodiment, the on-board diagnostic assembly <NUM> could work alone. Referring to <FIG>, in one embodiment, the on-board diagnostic assembly <NUM> could interface with a test reader, for example a diagnostic adapter <NUM>, e.g., a cell phone adapter, which connects the device <NUM> to a point of care diagnostic instrument <NUM>, e.g., a cell phone camera, for imaging and analysis of the sample results.

Referring to <FIG>, in other embodiments, the blood chamber outlet <NUM> (<FIG>) is in fluid communication with a portion of the interior <NUM> of the outer housing <NUM>.

Referring to <FIG>, in one embodiment, the device <NUM> directs the discard blood or cells <NUM> into the bottom of the interior <NUM> of the outer housing <NUM> during plasma separation. The plasma <NUM> is collected into a dispenser unit or dispenser assembly <NUM> that is removably connectable to a portion of the outer housing <NUM>. Referring to <FIG>, in one embodiment, the dispenser unit <NUM> is removed with the closure <NUM>. The separation chip <NUM> and discard blood or cells <NUM> remain in the outer housing <NUM> and are discarded. Referring to <FIG>, in one embodiment, the plasma <NUM> can then be dispensed for testing using the dispenser unit <NUM>.

Claim 1:
A biological fluid separation device (<NUM>) adapted to receive a blood sample (<NUM>) having a first portion (<NUM>) and a second portion (<NUM>), the biological fluid separation device comprising:
a housing (<NUM>) having an inlet (<NUM>) and an outlet (<NUM>);
a blood chamber (<NUM>) having a blood chamber inlet (<NUM>) and a blood chamber outlet (<NUM>), the blood chamber (<NUM>) adapted to receive the blood sample;
a separated chamber (<NUM>) having a chamber outlet (<NUM>);
a separator (<NUM>) disposed between the blood chamber (<NUM>) and the separated chamber (<NUM>), the separator (<NUM>) adapted to trap the first portion (<NUM>) in the blood chamber (<NUM>) and allow the second portion (<NUM>) to pass through the separator (<NUM>) into the separated chamber (<NUM>); and
an outer housing (<NUM>) removably connectable to the housing (<NUM>),
wherein the outer housing (<NUM>) contains a first vacuum (<NUM>) and the housing (<NUM>) contains a second vacuum (<NUM>),
wherein, with the housing (<NUM>) connected to the outer housing (<NUM>), the housing (<NUM>) is disposed within the outer housing (<NUM>),
wherein the first vacuum (<NUM>) and the second vacuum (<NUM>) are in communication via a venting plug (<NUM>, <NUM>), wherein
the housing (<NUM>) comprising a cap (<NUM>) removably attachable to the outlet (<NUM>), the cap (<NUM>) having the venting plug (<NUM>, <NUM>), characterised in that the venting plug (<NUM>, <NUM>) allows air to pass therethrough and prevents the second portion (<NUM>) of the blood sample (<NUM>) from passing therethrough.