Patent Description:
The present disclosure relates generally to devices adapted for use with biological fluids. More particularly, the present disclosure relates to devices adapted for separating components of biological fluids.

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 whole blood or cellular portion and a plasma portion. Plasma separation from whole blood has been traditionally achieved by centrifugation which typically takes <NUM> to <NUM> minutes and involves heavy labor or complex work flow. Recently there are other technologies that have been used or tried to separate plasma such as sedimentation, fibrous or non-fibrous membrane filtration, lateral flow separation, microfluidics cross flow filtration and other microfluidics hydrodynamic separation techniques. However many of those technologies have various challenges arranging from poor plasma purity, analyte bias or requiring specific coating to prevent analyte bias, high hemolysis, requiring dilution, long separation time, and/or difficult to recover the plasma. For example, most membrane based separation technologies suffer from an analyte bias problem, and often require specific coating treatments for the target analytes. Additionally, conventional separation technologies that occur while the device is directly connected to a patient thru a needle cause patient discomfort.

<CIT> discloses a known blood separation and collection device.

The present disclosure provides a blood separation device in accordance with independent claim <NUM> that decouples and separates the blood collection process from the plasma separation process. The blood separation device includes a sample collection module, an activation module, and a separation module. Because the plasma separation happens after the blood separation device is disconnected from a patient, the device performance is no longer affected by patient blood pressure and needle gauge, and patient discomfort is greatly reduced.

The present disclosure provides a blood separation device and a separation process that is fully compatible with a venous blood collection workflow without the need of centrifugation and power. Advantageously, the blood separation device of the present disclosure allows for the immediate separation of plasma during clinical blood draws and the ability for collection of the separated plasma sample in a self-contained plasma container for downstream diagnostics.

Furthermore, the blood separation device of the present disclosure provides for a separation device that only needs a short on-patient collection time that is no different than a conventional blood collection device using vacuum tubes, such as a BD Vacutainer® blood collection tube commercially available from Becton, Dickinson and Company, and corresponding venous access sets. Additionally, since the plasma separation happens after the device is disconnected from the patient, the device performance is no longer affected by patient blood pressure and needle gauge, and patient discomfort is greatly reduced.

Because the blood separation device of the present disclosure decouples and separates the blood collection process from the plasma separation process, the volume of the plasma generated is no longer limited by the allowable blood collection time on-patient. This enables the potential use of the blood separation device of the present disclosure for other high volume plasma applications beyond point of care.

Furthermore, another benefit of decoupling the separation from the collection process is that the separation time, plasma quality, and yield is no longer affected by the needle gauge and patient blood pressure. If the separation happens while a device is directly connected to a patient thru a needle, lower needle gauge and higher patient blood pressure reduce the separation time, yield and increases the hemolysis, whereas higher needle gauge and lower patient blood pressure increases the separation time, yield and decreases the hemolysis. By isolating the plasma separation process from the blood collection workflow using a blood separation device of the present disclosure, the blood collection sets and patient blood pressure will only affect the blood collection time while not varying the separation time, yield and hemolysis level.

In accordance with the present invention, a blood separation device adapted to receive a blood sample having a first phase and a second phase includes a sample collection module having a housing defining a collection chamber; an activation module connected to the sample collection module, the activation module having a first seal and a second seal for sealing the housing, the first seal transitionable from a closed position in which the collection chamber has a first pressure to an open position, by actuation of a portion of the activation module, in which the collection chamber is in fluid communication with a second pressure greater than the first pressure; and a separation module in fluid communication with the collection chamber of the sample collection module, the separation module may be defined as a first chamber having a first volume and a second chamber having a second volume and including a separation member disposed between the first chamber and the second chamber, wherein the first volume and the second volume are different.

In one configuration, the activation module includes a switch, wherein actuation of the switch transitions the first seal to the open position. In another configuration, the switch comprises a push button defining a vent hole therethrough and a piercing portion, wherein actuation of the switch moves the piercing portion to break the first seal thereby transitioning the first seal to the open position. In yet another configuration, with the first seal in the open position, the collection chamber of the sample collection module is in fluid communication with the second pressure via the vent hole of the switch. In one configuration, the second seal comprises a cap having a pierceable self-sealing stopper within a portion of the cap. In another configuration, the blood separation device is connectable to a blood collection device via the cap. In yet another configuration, the activation module defines an inlet channel, and wherein with the blood collection device connected to the blood separation device via the cap, the collection chamber receives the blood sample via the inlet channel. In one configuration, the collection chamber includes an inlet end and an exit end and defines a plurality of sequential flow direction alternating collection channels. In another configuration, the collection chamber includes an inlet end and an exit end and defines a first collection channel extending from the inlet end to the exit end, a second collection channel in communication with a portion of the first collection channel and extending from the exit end to the inlet end, and a third collection channel in communication with a portion of the second collection channel and extending from the inlet end to the exit end. In yet another configuration, the inlet end of the collection channels is in fluid communication with the inlet channel of the activation module. In one configuration, the blood sample travels through the first collection channel in a first direction, the blood sample travels through the second collection channel in a second direction opposite the first direction, and the blood sample travels through the third collection channel in a third direction opposite the second direction. In another configuration, the first collection channel is spaced from the second collection channel which is spaced from the third collection channel. In yet another configuration, the first chamber includes a first chamber inlet and a first chamber outlet, and the second chamber includes a second chamber outlet. In one configuration, the first chamber inlet is in fluid communication with the exit end of the collection channels. In another configuration, with the first seal in the open position, a first pressure difference between the second pressure defined by atmospheric pressure and the first pressure defined within the collection chamber draws the blood sample into the first chamber. In yet another configuration, with the first seal in the open position, the first volume and the second volume being different provides a second pressure difference between the first chamber and the second chamber to drive the second phase of the blood sample through the separation member into the second chamber. In one configuration, the separation member traps the first phase in the first chamber and allows the second phase to pass through the separation member into the second chamber. In another configuration, the blood separation device includes a second phase collection container in communication with the second chamber outlet, wherein the second phase collection container receives the second phase. In yet another configuration, the blood separation device includes a blood sample discard chamber in communication with the first chamber outlet, wherein the blood sample discard chamber receives the first phase. In one configuration, the separation member comprises a track-etched membrane. In another configuration, with the blood collection device connected to the blood separation device via the cap, the collection chamber receives the blood sample via the inlet channel. In yet another configuration, with the blood collection device disconnected from the blood separation device, and wherein upon actuation of the switch to transition the first seal to the open position, the first pressure difference between the second pressure defined by atmospheric pressure and the first pressure defined within the collection chamber draws the blood sample into the first chamber. In one configuration, with the first seal in the open position, the first volume and the second volume being different provides the second pressure difference between the first chamber and the second chamber to drive the second phase of the blood sample through the separation member into the second chamber. In another configuration, with the second phase contained within the second phase collection container, the second phase collection container is removable from the blood separation device. In yet another configuration, the first phase is a cellular portion and the second phase is a plasma portion.

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.

The following description is provided to enable those skilled in the art to make and use the described embodiments contemplated for carrying out the invention.

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> and <FIG> illustrate an exemplary embodiment of a blood separation device of the present disclosure. Referring to <FIG> and <FIG>, a blood separation device <NUM> of the present disclosure is adapted to receive a biological fluid, such as a blood sample <NUM> (<FIG>) having a first phase <NUM> and a second phase <NUM>. The first phase <NUM> of the blood sample <NUM> is a cellular portion and the second phase <NUM> of the blood sample <NUM> is a plasma portion.

A blood separation device <NUM> of the present disclosure decouples and separates the blood collection process from the plasma separation process. Because the plasma separation happens after the blood separation device <NUM> is disconnected from a patient, the device performance is no longer affected by patient blood pressure and needle gauge, and patient discomfort is greatly reduced.

Because the blood separation device <NUM> of the present disclosure decouples and separates the blood collection process from the plasma separation process, the volume of the plasma generated is no longer limited by the allowable blood collection time on-patient. This enables the potential use of the blood separation device <NUM> of the present disclosure for other high volume plasma applications beyond point of care.

The present disclosure provides a blood separation device <NUM> and a separation process that is fully compatible with a venous blood collection workflow without the need of centrifugation and power. Advantageously, the blood separation device <NUM> of the present disclosure allows for the immediate separation of plasma during clinical blood draws, with the device <NUM> off-patient, and the ability for collection of the separated plasma <NUM> sample in a self-contained plasma container, e.g., a second phase or plasma collection container <NUM>, for downstream diagnostics.

Furthermore, the blood separation device <NUM> of the present disclosure provides for a separation device that only needs a short on-patient collection time that is no different than a conventional blood collection device using vacuum tubes, such as a BD Vacutainer® blood collection tube commercially available from Becton, Dickinson and Company, and corresponding venous access sets. Additionally, since the plasma separation happens after the device <NUM> is disconnected from the patient, the device performance is no longer affected by patient blood pressure and needle gauge, and patient discomfort is greatly reduced.

Furthermore, another benefit of decoupling the plasma separation process from the collection process is that the separation time, plasma quality, and yield is no longer affected by the needle gauge and patient blood pressure. If the plasma separation process occurs while a device is directly connected to a patient thru a needle, lower needle gauge and higher patient blood pressure reduce the separation time, yield and increases the hemolysis, whereas higher needle gauge and lower patient blood pressure increases the separation time, yield and decreases the hemolysis. By isolating the plasma separation process from the blood collection process using a blood separation device <NUM> of the present disclosure, the blood collection sets and patient blood pressure will only affect the blood collection time while not varying the separation time, yield and hemolysis level.

Referring to <FIG>, in an exemplary embodiment, a blood separation device <NUM> generally includes a sample collection module <NUM>, an activation module <NUM>, and a separation module <NUM>. In one embodiment, after collecting a blood sample <NUM>, the blood separation device <NUM> is able to separate a second phase <NUM> of the blood sample <NUM> from a first phase <NUM> of the blood sample <NUM> as described in more detail below. Advantageously, the blood separation device <NUM> decouples and separates the blood collection process from the plasma separation process. In one embodiment, after plasma separation, a portion that is removable, e.g., a second phase collection container <NUM>, from the blood separation device <NUM> is able to transfer the second phase <NUM> of the blood sample <NUM> to a point-of-care testing device.

Referring to <FIG> and <FIG>, in an exemplary embodiment, the sample collection module <NUM> includes a housing <NUM> defining a collection chamber <NUM>. In accordance with the invention the collection chamber <NUM> includes an inlet end or inlet <NUM> and an exit end or exit <NUM> and defines a plurality of sequential flow direction alternating collection channels <NUM>.

The collection chamber <NUM> utilizes multiple interconnected parallel channels <NUM> to maximize collection and storage space within the constrained diameter of a blood collection set and also to ensure that the capillary force dominates over gravity during filling. A blood sample <NUM> fills the interconnected channels <NUM> of the sample collection module <NUM> in a back-and-forth motion as shown in <FIG>.

For example, referring to <FIG>, in a first exemplary embodiment, the collection chamber <NUM> of the sample collection module <NUM> defines a first collection channel <NUM> extending from the inlet end <NUM> to the exit end <NUM>, a second collection channel <NUM> in communication with a portion of the first collection channel <NUM> and extending from the exit end <NUM> to the inlet end <NUM>, and a third collection channel <NUM> in communication with a portion of the second collection channel <NUM> and extending from the inlet end <NUM> to the exit end <NUM>. Referring to <FIG>, the first collection channel <NUM> is spaced from the second collection channel <NUM> which is spaced from the third collection channel <NUM>.

In this manner, referring to the arrow in <FIG> indicating a flow path <NUM> of the blood sample <NUM> through the channels <NUM> of the collection chamber <NUM>, a blood sample <NUM> collected into the collection chamber <NUM> travels through the first collection channel <NUM> in a first direction, the blood sample <NUM> travels through the second collection channel <NUM> in a second direction opposite the first direction, and the blood sample <NUM> travels through the third collection channel <NUM> in a third direction opposite the second direction. Referring to <FIG>, the collection chamber <NUM> utilizes multiple interconnected parallel channels <NUM> to maximize collection and storage space within the constrained diameter of a blood collection set and also to ensure that the capillary force dominates over gravity during filling.

In one embodiment, the entrance into the collection chamber <NUM> is the inlet <NUM> of the first collection channel <NUM> and the exit out of the collection chamber <NUM> is the exit <NUM> of the third collection channel <NUM>. The inlet <NUM> of the first collection channel <NUM> is in fluid communication with an inlet channel <NUM> (<FIG> and <FIG>) of the activation module <NUM>, as described in more detail below.

Referring to <FIG>, in a second exemplary embodiment, the collection chamber <NUM> of the sample collection module <NUM> defines a first collection channel <NUM> extending from the inlet end <NUM> to the exit end <NUM>, a second collection channel <NUM> in communication with a portion of the first collection channel <NUM> and extending from the exit end <NUM> to the inlet end <NUM>, a third collection channel <NUM> in communication with a portion of the second collection channel <NUM> and extending from the inlet end <NUM> to the exit end <NUM>, a fourth collection channel <NUM> in communication with a portion of the third collection channel <NUM> and extending from the exit end <NUM> to the inlet end <NUM>, and a fifth collection channel <NUM> in communication with a portion of the fourth collection channel <NUM> and extending from the inlet end <NUM> to the exit end <NUM>. Referring to <FIG>, the first collection channel <NUM> is spaced from the second collection channel <NUM> which is spaced from the third collection channel <NUM> which is spaced from the fourth collection channel <NUM> which is spaced from the fifth collection channel <NUM>.

In this manner, a blood sample <NUM> collected into the collection chamber <NUM> travels through the first collection channel <NUM> in a first direction, the blood sample <NUM> travels through the second collection channel <NUM> in a second direction opposite the first direction, the blood sample <NUM> travels through the third collection channel <NUM> in a third direction opposite the second direction, the blood sample <NUM> travels through the fourth collection channel <NUM> in a fourth direction opposite the third direction, and the blood sample <NUM> travels through the fifth collection channel <NUM> in a fifth direction opposite the fourth direction. Referring to <FIG>, the collection chamber <NUM> utilizes multiple interconnected parallel channels <NUM> to maximize collection and storage space within the constrained diameter of a blood collection set and also to ensure that the capillary force dominates over gravity during filling.

In one embodiment, the entrance into the collection chamber <NUM> is the inlet <NUM> of the first collection channel <NUM> and the exit out of the collection chamber <NUM> is the exit <NUM> of the fifth collection channel <NUM>. The inlet <NUM> of the first collection channel <NUM> is in fluid communication with an inlet channel <NUM> (<FIG> and <FIG>) of the activation module <NUM>, as described in more detail below.

In other exemplary embodiments, the collection chamber <NUM> of the sample collection module <NUM> may define any odd number of channels <NUM> based on a specific volume requirement. Importantly, the collection chamber <NUM> of the sample collection module <NUM> utilizes multiple interconnected parallel channels <NUM> to maximize collection and storage space within the constrained diameter of a blood collection set and also to ensure that the capillary force dominates over gravity during filling. A blood sample <NUM> fills the interconnected channels <NUM> of the sample collection module <NUM> in a back-and-forth motion as described above.

In one exemplary embodiment, the plurality of sequential flow direction alternating collection channels <NUM> are configured in a parallel configuration as shown in <FIG>. In other exemplary embodiments, the collection channels <NUM> are configured in a spiral or meandering channel configuration or in other configurations that maximize collection and storage space within the constrained diameter of a blood collection set and also to ensure that the capillary force dominates over gravity during filling.

In an exemplary embodiment, the collection chamber <NUM> is designed to ensure that the blood <NUM> fills the channels <NUM> of the collection chamber <NUM> continuously without trapping air bubbles regardless of device orientation and blood flow rate. This is accomplished by controlling the diameter of the channels <NUM> for desired applications. For example, in an exemplary embodiment, to prevent the blood stream from breaking up and trapping air bubbles, the diameter of the channels <NUM> needs to simultaneously meet two requirements. First, the static pressure difference at the flow front at any orientation needs to be smaller than the Laplace pressure so that the meniscus will hold its shape. Second, the selected diameter needs to make sure that the inertia force is smaller than the surface tension at the highest flow rate.

Referring to <FIG>, <FIG>, and <FIG>, in an exemplary embodiment, the activation module <NUM> is connected or connectable to the sample collection module <NUM> and includes a housing <NUM>, a first seal <NUM>, and a second seal <NUM> for sealing the blood separation device <NUM>, e.g., the housing <NUM> of the sample collection module <NUM>, the housing <NUM> of the activation module <NUM>, and a housing <NUM> of the separation module <NUM>. In this manner, the seals <NUM>, <NUM> of the activation module <NUM> control the pressure within the blood separation device <NUM> as described in more detail below. The first seal <NUM> is transitionable from a closed position (<FIG>) in which the collection chamber <NUM> has a first pressure P1 (<FIG>) to an open position (<FIG>), by actuation of a portion of the activation module <NUM>, in which the collection chamber <NUM> is in fluid communication with a second pressure P2 (<FIG>) greater than the first pressure P1.

In an exemplary embodiment, referring to <FIG>, the activation module <NUM> includes a switch <NUM>. In such an embodiment, actuation of the switch <NUM> transitions the first seal <NUM> from the closed position (<FIG>) to the open position (<FIG>). Referring to <FIG>, the switch <NUM> comprises a push button <NUM> defining a vent hole <NUM> therethrough and a piercing portion <NUM>. In this manner, actuation of the switch, e.g., depressing or pushing the push button <NUM> into the position shown in <FIG>, moves the piercing portion <NUM> to break the first seal <NUM> thereby transitioning the first seal <NUM> to the open position.

With the first seal <NUM> in the open position, the collection chamber <NUM> of the sample collection module <NUM> is in fluid communication with a second pressure P2 via the vent hole <NUM> of the switch <NUM>. The vent hole <NUM> provides a venting mechanism for the blood separation device <NUM>. For example, in one embodiment, the piercing portion <NUM> breaks the first seal <NUM>, e.g., an aluminum foil seal, to create a vent to power the plasma separation process.

The second pressure P2 defined by atmospheric pressure is greater than the first pressure P1 defined within the blood separation device <NUM>, e.g., the collection chamber <NUM> of the sample collection module <NUM>. In this manner, the pressure difference between the second pressure P2 defined by atmosphere pressure and the residual vacuum in the blood separation device <NUM>, i.e., the first pressure P1 defined within the blood separation device <NUM>, continuously drive the plasma separation process as described in more detail below. Advantageously, using the activation module <NUM> of the present disclosure, a user can precisely control when the plasma separation process begins.

In an exemplary embodiment, referring to <FIG>, the second seal <NUM> of the activation module <NUM> includes a cap <NUM> having a pierceable self-sealing stopper <NUM> within a portion of the cap <NUM>. The cap <NUM> provides a mechanism for allowing the blood separation device <NUM> to be connectable to a blood collection device <NUM> (<FIG>) as described in more detail below.

Referring to <FIG>, in one embodiment, the activation module <NUM> defines an inlet channel <NUM>. Referring to <FIG>, with a blood collection device <NUM> connected to the blood separation device <NUM> via the cap <NUM>, the collection chamber <NUM> of the sample collection module <NUM> receives a blood sample <NUM> via the inlet channel <NUM>. A blood sample <NUM> flows from the inlet channel <NUM> of the activation module <NUM> to the plurality of channels <NUM> of the collection chamber <NUM> via the inlet <NUM>.

Referring to <FIG> and <FIG>, in an exemplary embodiment, the separation module <NUM> is in fluid communication with the collection chamber <NUM> of the sample collection module <NUM> and includes a housing <NUM> and defines a first chamber <NUM> having a first volume V1 (<FIG>) and a second chamber <NUM> having a second volume V2 (<FIG>) and including a separation member <NUM> disposed between the first chamber <NUM> and the second chamber <NUM>. The first volume V1 of the first chamber <NUM> and the second volume V2 of the second chamber <NUM> are different to create a second pressure difference between the first chamber <NUM> and the second chamber <NUM> to drive the second phase <NUM> of a blood sample <NUM> through the separation member <NUM> into the second chamber <NUM> as described in more detail below. In one embodiment, a portion of the separation module <NUM> forms a microfluidic chip.

Referring to <FIG> and <FIG>, in an exemplary embodiment, the separation member <NUM> traps the first phase <NUM> in the first chamber <NUM> and allows the second phase <NUM> to pass through the separation member <NUM> into the second chamber <NUM>. In one embodiment, the separation member <NUM> comprises a track-etched membrane. In certain configurations, the membrane may be less than <NUM> microns in thickness, such as from <NUM> to <NUM> microns in thickness. The membrane may have submicron pores or holes, such as from <NUM> to <NUM> microns in diameter. This dimensionality allows for continuous filtering of a plasma portion of a blood sample flowing parallel to the membrane surface, which prevents clogging of the membrane pores or holes. In other embodiments, the separation member <NUM> may comprise any filter, and/or any other separation device, that is able to trap the first phase <NUM> in the first chamber <NUM> and allow the second phase <NUM> to pass through the separation member <NUM> into the second chamber <NUM>.

Referring to <FIG> and <FIG>, the first chamber <NUM> includes a first chamber inlet <NUM> and a first chamber outlet <NUM>, and the second chamber <NUM> includes a second chamber outlet <NUM>. The first chamber inlet <NUM> is in fluid communication with the exit <NUM> of the collection channels <NUM>. In this manner, upon actuation of a portion of the activation module <NUM>, a blood sample <NUM> can flow from the collection chamber <NUM> of the sample collection module <NUM> to the first chamber <NUM> of the separation module <NUM> for plasma separation.

Referring to <FIG>, <FIG>, and <FIG>, the separation module <NUM> of the blood separation device <NUM> includes a second phase collection container <NUM> that is in communication with the second chamber outlet <NUM>. The second phase collection container <NUM> receives the second phase <NUM> of the blood sample <NUM>. The second phase collection container <NUM> is able to collect and store the separated second phase <NUM>. Advantageously, referring to <FIG>, with the second phase <NUM> contained within the second phase collection container <NUM>, the second phase collection container <NUM> is removable from the blood separation device <NUM>. In this manner, the second phase <NUM> of a blood sample <NUM> can be collected or stored in a secondary second phase container, e.g., a second phase collection container <NUM>, for further diagnostic tests. For example, after separation, with the second phase collection container <NUM> removed from the blood separation device <NUM>, the second phase collection container <NUM> is able to transfer the second phase <NUM> of the blood sample <NUM> to a point-of-care testing device or other testing device. In an exemplary embodiment, the second phase collection container <NUM> includes structure allowing the second phase collection container <NUM> to dispense a portion of the plasma <NUM>, when desired. In one embodiment, the second phase collection container <NUM> is sealed via a cap or septum <NUM> to protectively seal the plasma portion <NUM> within the second phase collection container <NUM>.

Referring to <FIG>, in an exemplary embodiment, a portion of the second chamber <NUM> of the separation module <NUM> is in fluid communication with an interior of the second phase collection container <NUM> to allow the plasma portion <NUM> to flow through the separation member <NUM> and the second chamber <NUM> into the interior of the second phase collection container <NUM> for collection.

Referring to <FIG>, the separation module <NUM> of the blood separation device <NUM> also includes a blood sample discard chamber <NUM> that is in communication with the first chamber outlet <NUM>. The blood sample discard chamber <NUM> receives the remaining first phase <NUM> of the blood sample <NUM> after a blood sample <NUM> flows over the separation member <NUM> in the first chamber <NUM>. In this manner, the remaining first phase <NUM> of the blood sample <NUM> can be collected and stored in the blood sample discard chamber <NUM>. Also, the blood sample discard chamber <NUM> ensures that the remaining first phase <NUM> of the blood sample <NUM> can be safely stored when the rest of the blood separation device <NUM> is discarded after use.

Referring to <FIG>, use of a blood separation device <NUM> of the present disclosure will now be described.

Referring to <FIG>, a first step of using a blood separation device <NUM> of the present disclosure involves collecting a blood sample <NUM> from a patient, e.g., the blood collection process. For example, first, a given volume of a blood sample <NUM> from a patient is pulled into the collection chamber <NUM> of the blood separation device <NUM> under a vacuum force, immediately following the connection of the blood separation device <NUM> to a blood collection device <NUM>, such as a tube holder <NUM>. In one embodiment, such a connection consists of a non-patient needle (not shown) of the tube holder <NUM> piercing the stopper <NUM> of the cap (<FIG>). The opposite end of a line <NUM> of the tube holder <NUM> consists of a patient needle of a venous access set in communication with a patient.

Referring to <FIG>, with the tube holder <NUM> of the blood collection device <NUM> connected to the blood separation device <NUM> via the cap <NUM> (<FIG>), the collection chamber <NUM> of the sample collection module <NUM> receives the blood sample <NUM> via the inlet channel <NUM> (<FIG>) of the activation module <NUM>. The blood separation device <NUM> of the present disclosure collects and stores a fixed amount of the patient's blood. In one exemplary embodiment, a blood separation device <NUM> of the present disclosure collects and stores <NUM> of a patient's blood in less than <NUM> seconds.

The blood sample <NUM> flows through the inlet channel <NUM> of the activation module <NUM> to the collection chamber <NUM> of the sample collection module <NUM>. Advantageously, during blood collection, the plurality of sequential flow direction alternating collection channels <NUM> of the collection chamber <NUM> maximize collection and storage space within the constrained diameter of a blood collection set and also to ensure that the capillary force dominates over gravity during filling.

A user can select one of the ways, sources, or methods that the blood separation device <NUM> is able to receive a blood sample <NUM>. For example, referring to <FIG>, the blood separation device <NUM> of the present disclosure is able to receive a blood sample <NUM> from a conventional blood collection device <NUM>. For example, the blood collection device <NUM> may include a tube holder <NUM> and corresponding venous access set, such as a BD Vacutainer® blood collection tube commercially available from Becton, Dickinson and Company. In other alternative embodiments, blood is collected in a conventional blood collection tube or any other intermediate blood sample container. The blood sample container is then connected to the off-patient separation device to generate plasma.

Once a desired amount of a blood sample <NUM> is collected into the collection chamber <NUM> and the blood collection process is complete, the blood separation device <NUM> is disconnected from the blood collection device <NUM>. In this manner, a blood separation device <NUM> of the present disclosure decouples and separates the blood collection process from the plasma separation process. Because the plasma separation happens after the blood separation device <NUM> is disconnected from the patient, the device performance is no longer affected by patient blood pressure and needle gauge, and patient discomfort is greatly reduced.

Upon disconnection of the blood separation device <NUM> of the present disclosure from the blood collection device <NUM> and the patient, the collected blood remains stationary in the channels <NUM> until the plasma separation is activated. The blood separation device <NUM> accomplishes this by utilizing the second seal <NUM>, e.g., the stopper <NUM> of the cap <NUM>. The stopper <NUM> of the cap <NUM> ensures that the second seal <NUM> is properly resealed after a needle of the blood collection device <NUM> is retracted out from the stopper <NUM> so that there is no pressure difference between the front and back end of the stored blood within the blood separation device <NUM>.

Referring to <FIG>, after the blood separation device <NUM> is disconnected from the blood collection device <NUM>, the plasma separation process can be started. Advantageously, the blood separation device <NUM> of the present disclosure does not require being connected to a patient to perform plasma separation. The plasma separation process is completely controllable and can be started at a convenient and desired time.

Referring to <FIG>, the plasma separation process is started with the blood separation device <NUM> off-patient by simply actuating the switch <NUM> (<FIG>), e.g., pushing the push button <NUM>, on the blood separation device <NUM>. Actuation of the switch <NUM> allows the blood separation device <NUM> to automatically generate plasma <NUM> from the blood sample <NUM> stored within the blood separation device <NUM>.

Actuation of the switch <NUM> transitions the first seal <NUM> to the open position (<FIG>), in which the collection chamber <NUM> is in fluid communication with a second pressure P2 defined by atmospheric pressure that is greater than the first pressure P1 defined within the collection chamber <NUM>. In this manner, the first pressure difference, e.g., the difference in pressure between the second pressure P2 defined by atmospheric pressure and the first pressure P1 defined within the collection chamber <NUM>, draws the blood sample <NUM> into the first chamber <NUM> of the separation module <NUM>. In other words, the first pressure difference between the atmosphere pressure and the residual vacuum in the blood separation device <NUM> continuously drives the plasma separation within the blood separation device <NUM>. In an exemplary embodiment, the separation module <NUM> allows for continuous plasma separation as a blood sample <NUM> flows through the first chamber <NUM> and over the separation member <NUM> by utilizing a cross-flow filtration flow pattern in a microfluidic chip, e.g., the separation module <NUM> as shown in <FIG>. In one configuration, the pressure in the collection chamber <NUM> is limited by the maximum allowable pressure difference across the membrane such that the end point pressure within the collection chamber <NUM> after blood collection and before filtration should be smaller than <NUM> kPa (<NUM> psi).

Advantageously, the activation module <NUM> starts the plasma separation process after blood collection and with the blood separation device <NUM> disconnected from a blood collection device <NUM> and a patient. To start the plasma separation process after blood collection, it is essential to re-establish a pressure gradient on the stored blood within the collection chamber <NUM>. This is accomplished via the activation module <NUM> controlling the pressures within the blood separation device <NUM>. Before activation, the first seal <NUM> and the second seal <NUM> of the activation module <NUM> seal the housing <NUM> of the blood separation device <NUM> and with the first seal <NUM> in the closed position (<FIG>), the activation module <NUM> seals the collection chamber <NUM> at a first pressure P1. After activation of the activation module <NUM>, the first seal <NUM> is transitioned to the open position (<FIG>), in which the collection chamber <NUM> is in fluid communication with a second pressure P2 defined by atmospheric pressure that is greater than the first pressure P1 defined within the collection chamber <NUM>.

Importantly, a second pressure difference is used within the blood separation device <NUM> to drive the plasma <NUM> to pass through the separation member <NUM> into the second chamber <NUM> and be collected within the second phase collection container <NUM>. With the first seal <NUM> in the open position (<FIG>), the first volume V1 of the first chamber <NUM> of the separation module <NUM> and the second volume V2 of the second chamber <NUM> of the separation module <NUM> being different provides the second pressure difference between the first chamber <NUM> and the second chamber <NUM> to drive the second phase <NUM> of the blood sample <NUM> through the separation member <NUM> into the second chamber <NUM> and to be collected within the second phase collection container <NUM>. In other words, the second pressure difference across the blood flow in the first chamber <NUM> and the plasma flow path in the second chamber <NUM> and their dynamic profiles during the separation provides a power source that further drives the plasma separation process. In an exemplary embodiment, controlling the second pressure difference across the blood flow in the first chamber <NUM> and the plasma flow path in the second chamber <NUM> and their dynamic profiles for a given plasma separation chip, e.g., separation module <NUM>, is achieved via setting the appropriate initial vacuum level and balancing the volume ratio of the blood sample discard chamber <NUM> and the second phase collection container <NUM>. In an exemplary embodiment, a volume of the blood sample discard chamber <NUM> is designed to ensure that the volume is big enough to have sufficient residual vacuum in the end to drive the blood flow without clogging the separation member <NUM>. In an exemplary embodiment, the volume also needs to be small enough so that at the end of the separation, the pressure in the blood sample discard chamber <NUM> is higher than a pressure in the second phase collection container <NUM> to keep the separation member <NUM> from collapsing. In one configuration, the volume of the blood sample discard chamber <NUM> is at least twice as large as the volume of the collection chamber <NUM>, and smaller than the volume of the second phase collection container <NUM> multiplied by the factor (<NUM>-yield)/yield. The pressure difference across the membrane may need to be smaller than <NUM> kPa (<NUM> psi) at all times during filtration.

Utilizing the first pressure difference and the second pressure difference within the blood separation device <NUM> forces the blood <NUM> to flow through the first chamber <NUM> and over the separation member <NUM>. As the blood <NUM> flows thru the separation module <NUM>, plasma <NUM> is continuously separated from the first phase <NUM> of the blood sample <NUM>.

During plasma separation, the separation member <NUM> allows the second phase or plasma <NUM> to pass through the separation member <NUM> into the second chamber <NUM> which can be collected or stored in a secondary plasma container, e.g., a second phase collection container <NUM>, for further diagnostic tests. Referring to <FIG>, the arrow comprising a broken line indicates the second phase flow path <NUM> that the plasma <NUM> takes after passing through the separation member <NUM>. In one embodiment, after plasma separation, with the second phase or plasma <NUM> contained within the second phase collection container <NUM>, the second phase collection container <NUM> is removable from the blood separation device <NUM>. The second phase collection container <NUM> can then be used to transfer the plasma portion <NUM> to a point-of-care testing device or other diagnostic testing system.

During plasma separation, the separation member <NUM> traps the first phase <NUM> of the blood sample <NUM> within the first chamber <NUM>, e.g., the first phase <NUM> of the blood sample <NUM> is not allowed to pass through the separation member <NUM> into the second chamber <NUM>. Referring to <FIG>, the arrow comprising a straight line indicates the flow path <NUM> that the blood sample <NUM> takes through the collection chamber <NUM> and the flow path <NUM> that the first phase <NUM> of the blood sample <NUM> takes after passing over the separation member <NUM> and to the blood sample discard chamber <NUM>. Referring to <FIG> and <FIG>, the first phase <NUM> of the blood sample <NUM> flows into the first chamber <NUM> through the first chamber inlet <NUM> and over the separation member <NUM> surface, and then exits the first chamber <NUM> via the first chamber outlet <NUM> into the blood sample discard chamber <NUM>.

In one exemplary embodiment, a blood separation device <NUM> of the present disclosure is able to generate <NUM> to <NUM> uL of plasma <NUM> from the stored <NUM> of blood in less than <NUM> minutes.

Referring to <FIG>, the blood separation device <NUM> of the present disclosure allows for plasma separation to occur independent of an orientation of the blood separation device <NUM>. In other words, the blood separation device <NUM> separates plasma regardless of whether the blood separation device <NUM> is in an upright orientation, e.g., the blood separation device <NUM> is contained in a tube rack, or if the blood separation device <NUM> is lying in a flat orientation on a table or tray.

Referring to <FIG>, with the second phase or plasma <NUM> contained within the second phase collection container <NUM>, the second phase collection container <NUM> is removable from the blood separation device <NUM>. The second phase collection container <NUM> can then be used to transfer the plasma portion <NUM> to a point-of-care testing device or other diagnostic testing system. In one embodiment, the second phase collection container <NUM> is removably connectable to the blood separation device <NUM> via a luer lock septum seal.

In other words, after plasma separation is completed, the plasma <NUM> within the second phase collection container <NUM> is removed from the blood separation device <NUM> for use in clinical tests. The rest of the blood separation device <NUM> can then be discarded.

As described herein, the present disclosure provides a blood separation device that decouples and separates the blood collection process from the plasma separation process. The blood separation device includes a sample collection module, an activation module, and a separation module. Because the plasma separation happens after the blood separation device is disconnected from the patient, the device performance is no longer affected by patient blood pressure and needle gauge, and patient discomfort is greatly reduced.

Claim 1:
A blood separation device adapted to receive a blood sample having a first phase and a second phase, the blood separation device comprising:
a sample collection module (<NUM>) having a housing (<NUM>) defining a collection chamber (<NUM>), characterized in that
the collection chamber (<NUM>) includes an inlet end or inlet (<NUM>) and an exit end or exit (<NUM>) and defines a plurality of interconnected parallel sequential flow direction alternating collection channels (<NUM>);
an activation module (<NUM>), wherein the activation module (<NUM>) comprises a first seal (<NUM>) and a second seal (<NUM>) for sealing the housing (<NUM>), the first seal (<NUM>) transitionable from a closed position in which the collection chamber (<NUM>) has a first pressure (P1) to an open position, by actuation of a portion of the activation module (<NUM>), in which the collection chamber (<NUM>) is in fluid communication with a second pressure (P2) greater than the first pressure (P1); and
a separation module (<NUM>) wherein the separation module is in fluid communication with the collection chamber (<NUM>) of the sample collection module (<NUM>).