Patent Description:
Whole blood (hereinafter "WB") donation procedures typically are conducted with the sole purposed of WB collection. However, there is a rise in development of new in vitro diagnostics (hereinafter "IVD"), which are tests done on samples, such as blood or tissue, taken from a human subject. IVD can detect diseases or other conditions and may be used to monitor overall health and to potentially to help cure, treat or prevent diseases. IVD also can be used in precision medicine to identify patients who are likely to benefit from specific treatments or therapies.

Lab-on-a-chip (hereinafter "LOC") devices are commonly used in IVD. Such devices integrate one or several laboratory functions on a single integrated circuit (or chip) to achieve automation and high-throughput screening. LOC devices can handle extremely small fluid volumes, down to less than pico-liters.

LOC technology may soon become an important part of efforts to improve global health, particularly through the development of point-of-care (hereinafter "POC") testing devices. In countries with few healthcare resources, infectious diseases that would be treatable in a developed nation are often deadly. In some cases, poor healthcare clinics have the drugs to treat a certain illness, but lack the diagnostic tools to identify patients who should receive the drugs. Many researchers believe that LOC technology may be a key to powerful new diagnostic instruments. The goal of these researchers is to create microfluidic chips that will allow healthcare providers to perform diagnostic tests such as immunoassays and nucleic acid assays with no laboratory support. Development of LOC devices may provide numerous advantages, which are specific to their application.

Within the field of IVD, small volumes of WB may be collected from patients for analysis of circulating biomarkers. The analysis of plasma biomarkers can diagnose many diseases, such as cancer, Alzheimer's disease, or sepsis. Typically, plasma is separated from WB before analysis to prevent contamination of the biomarkers by the presence of leukocytes, erythrocytes and hemolysis, which could increase test variability and reduce test accuracy.

The current state of the art for acquiring plasma for LOC devices consists of either using a traditional bench-top centrifuge or using plasma separation filters as for example described in <CIT>. In turn, each company developing a LOC device also develops its own in-vitro diagnostic device to collect biomarkers on a disposable cartridge. These separate processes and devices unfortunately do not lend themselves to point-of-care devices for wide-spread use or use during routine WB donations.

Insofar as the term embodiment or aspect or alternative is used in the following, or features are presented as being optional, this should be interpreted in such a way that the only protection sought is that of the invention claimed and defined in the appended claims.

The prospect of direct biomarker collection during WB donation could provide significant advantages in costs, efficiencies and timeliness. This may be facilitated by providing for use of LOC devices that provide for separation of biomarkers during WB donation, which will be the context for use of "LOC device(s)" hereinafter.

This disclosure seeks to provide a standardized blood pack donation system configured for use with a LOC device for biomarker separation and collection during WB donation. Many biotechnology companies are working to develop such LOC devices to separate, collect and/or detect biomarkers for diseases. These LOC devices typically require low flow rates as biomarkers are separated from WB. The invention of the present disclosure would provide a standardized blood pack donation system or kit, which would allow for LOC device testing during a routine blood donation procedure, such as for example a <NUM> WB donation. Thus, a blood pack device and methods of using the same of the present disclosure permit WB donation and facilitate simultaneous use of a LOC device for separation and collection of biomarkers for further analysis.

It will be appreciated that the blood pack donation systems disclosed herein are configured for use with any of a variety of LOC devices, which may be provided by various manufacturers for use in separation, collection and screening for any one or more of a number of different biomarkers. Thus, makers of LOC devices may integrate their respective devices for use in testing in blood donation centers, clinics, medical facilities or other locations where routine WB donation may be conducted. As such, WB donors would have an option of being screened for disease marking biomarkers during a routine WB donation procedure, such as for example a <NUM> WB donation. This would provide much broader access to biomarker screening and early disease detection for routine WB donors.

The availability of such an advantageous standardized blood pack donation system or kit for use with LOC devices in WB donation centers or other facilities would readily and conveniently enable screening many donors for disease biomarkers, while reducing costs and the logistics involved in developing and stocking individual systems from each manufacturer. It will be appreciated that this would be important to early diagnosis, prevention and treatment of cancer or any number of different diseases. A standardized system or kit may be coupled with a variety of LOC devices to yield many applications for any number of biomarkers. The convenience could prompt offers by blood donation centers, clinics or medical facilities to donate WB and screen for particular biomarkers, including but not limited to genetic material, cell free DNA, exosomes, or any particular bloodborne biomarker for a disease.

The system or kit may take advantage of microfluidics in line to the WB collection container. For example, flow may be driven via the donor's blood pressure. The WB collection container also may be relocated to hang at a greater height to reverse flow and return WB to the donor, if desired, such as during a multiple pass collection procedure. The potential to collect any biomarker by using a microfluidic or LOC device is quite broad. Thus, in a single pass collection procedure, depending on the configuration of the system, at least some of the WB that is collected during donation is run through a LOC device for separation, before reaching a WB collection container.

The WB collection container may have any configuration and selected volume and, when combined into the system, must have at least one opening. Thus, the opening may be preexisting and connected to a flow path, or may be formed when the WB collection container is being connected to a flow path within the system. In turn, the biomarkers separated out by the LOC device are collected and transferred to a biomarker collection container. The biomarker collection container also may have any configuration, such as a bag, tube, syringe or other suitable structure, and any selected volume, but generally will be much smaller than the WB collection container. When combined into the system, the biomarker collection container also must have at least one opening. Thus, the opening may be preexisting and connected to a flow path, or may be formed when the biomarker collection container is being connected to a flow path within the system.

An alternative second example system may be provided to utilize a single pass collection procedure or a multiple pass collection procedure. The second example system includes a bypass line or flow path between the donor and WB collection container. This permits procedures in which some, none or all of the WB bypasses the LOC device. The second example system may be employed in a multiple pass collection procedure, such as may include three steps. In the first step (step one), flow through the LOC device is permitted and flow through the bypass line or flow path may range from being fully or partially permitted to being prevented, depending on the portion of the donated WB intended to pass through the LOC device. Accordingly, at least some of the WB that is collected during donation from a donor is run through a LOC device for separation, before reaching a WB collection container. In turn, the biomarkers separated out by the LOC device are collected and transferred via a separate flow path to a biomarker collection container.

In a second step (step two) of the multiple pass collection procedure, flow is reversed from the WB collection container and all of the flow is permitted through the bypass line or flow path, while being entirely prevented from flowing back through the LOC device and thereby to the biomarker collection container. In a third step (step three), at least some of the WB that is collected during donation from a donor again is run through a LOC device for separation, before reaching the WB collection container. As with the first step, flow through the bypass line or flow path may range from being fully or partially permitted to being prevented. WB is collected again and at least some of the WB that is collected is run through the LOC device before reaching the WB collection container. The biomarkers separated out by the LOC device are collected and transferred to the biomarker collection container. Thus, upon completion of a multiple pass collection procedure, donated WB has been collected in the WB collection container, while biomarkers have been collected in the biomarker collection container.

In a first aspect, a blood pack donation system is configured for use with a LOC device for biomarker collection during WB donation including a blood collection container having a volume and at least one opening, a biomarker collection container having a volume and at least one opening, a first flow path having a first end connected to the opening in the blood collection container and a second end configured to be connected to a first outlet opening of the LOC device, a second flow path having a first end connected to the opening in the biomarker collection container and a second end configured to be connected to a second outlet opening of the LOC device, and a third flow path having a first end connected to a needle and a second end configured to be connected to an inlet opening of the LOC device. These components are present in first and second example systems, both of which are capable of being used in a single pass collection procedure.

In a second aspect, a blood pack donation system of the previous configuration may further include a fourth flow path having a first end connected to the first flow path at a location between the first end and second end of the first flow path and having a second end connected to the third flow path at a location between the first end and second end of the third flow path. The fourth flow path serves as the aforementioned bypass line or flow path between the donor and WB collection container, which permits bypassing the LOC device. The blood pack donation system also may include a plurality of flow control components that selectively control flow through the first flow path, third flow path and fourth flow path. The plurality of flow control components is selectively adjustable for use with a LOC device to provide a single pass collection procedure or a multiple pass collection procedure for collecting WB during a WB donation, while also collecting biomarkers. The multiple pass collection procedure includes a succession of adjustments of the plurality of flow control components.

It will be appreciated that a blood pack donation system configured for use with a LOC device for biomarker collection during WB donation may be constructed for use in advantageous, cost efficient and convenient single or multiple pass collection methods.

The embodiments disclosed herein are for the purpose of providing an exemplary description of the present subject matter. They are, however, only exemplary, and the present subject matter may be embodied in various forms. Therefore, specific details disclosed herein are not to be interpreted as limiting the subject matter as defined in the accompanying claims.

It will be appreciated that a blood pack donation system configured for use with a LOC device for biomarker collection during WB donation may be applicable for efficient and convenient use with a LOC device to screen for the presence of and collect biomarkers.

<FIG> illustrate two example embodiments of such blood pack donation systems. The first embodiment, shown in <FIG>, provides for a single pass collection procedure via connection to a LOC device, which permits collecting WB during a WB donation, while screening for and collecting biomarkers. The second embodiment, shown in <FIG>, provides for a single pass collection procedure or an optional multiple pass collection procedure via connection to a LOC device. The second embodiment includes a plurality of flow control components wherein a single pass collection procedure comparable to that of the first embodiment may be performed with the plurality of flow control components having first selected settings. The second embodiment permits a multiple pass collection procedure that may be performed with the plurality of flow control components having a succession of further second and third selected settings, and which permits collecting WB during a WB donation, while screening for and collecting biomarkers.

Turning now to <FIG>, a blood pack donation system <NUM> is configured for use with a LOC device <NUM> for biomarker collection during WB donation. Thus, the blood pack donation system <NUM> preferably is presterilized and configured for use with any of a variety of LOC devices <NUM>, which may be provided by various manufacturers for use in separating and screening for collection any of a number of different biomarkers. Thus, makers of LOC devices may construct or integrate their LOC devices for use with the system <NUM>.

The system <NUM> includes a blood collection container <NUM> having a volume and at least one opening <NUM>, and a biomarker collection container <NUM> having a volume and at least one opening <NUM>. A first flow path <NUM> having a first end <NUM> is connected to the opening <NUM> in the blood collection container <NUM> and a second end <NUM> is configured to be connected to a first outlet opening <NUM> of the LOC device <NUM>. A second flow path <NUM> having a first end <NUM> is connected to the opening <NUM> in the biomarker collection container <NUM> and a second end <NUM> configured to be connected to a second outlet opening <NUM> of the LOC device <NUM>. A third flow path <NUM> having a first end <NUM> is connected to a needle <NUM> and a second end <NUM> configured to be connected to an inlet opening <NUM> of the LOC device <NUM>. The needle <NUM> is configured for use with a donor D, for use in the manner of a routine WB donation procedure.

As noted above, the respective openings in the blood collection container <NUM> and biomarker collection container <NUM> may be preexisting or formed when connected to a respective flow path <NUM>, <NUM>. In addition, the flow paths may be constructed in the form of individual sections of tubing, or may be integrated into a cassette, whether in the form of channels or sections of tubing. It will be appreciated that the first example system <NUM> may have an alternative configuration in the form of a cassette, which may provide the respective flow paths already connected to a housing, which may be represented by the body <NUM>, which in turn may accept a LOC device for connection to the respective flow paths for use.

As previously noted, the blood pack donation system <NUM> preferably is presterilized. The system <NUM> may be configured with integrated fixed connections between all or some of the components, such as via heat sealing, solvent bonding or other suitable means of connection. Connectors may be used to permanently join separated components. In a further alternative, all or some of the connections may be removably connected, such as by means of sterile unions using Luer-Lock connectors, or other suitable connection devices.

For example, the opening <NUM> of the blood collection container <NUM> may be removably connected to the first end <NUM> of the first flow path <NUM>, and the first outlet opening <NUM> of the LOC device <NUM> may be removably connected to the second end <NUM> of the first flow path <NUM>. Similarly, the opening <NUM> of the biomarker collection container <NUM> may be removably connected to the first end <NUM> of the second flow path <NUM>, and the second outlet opening <NUM> of the LOC device <NUM> may be removably connected to the second end <NUM> of the second flow path <NUM>. In turn, the needle <NUM> may be removably connected to the first end <NUM> of the third flow path <NUM>, and the inlet opening <NUM> of the LOC device <NUM> may be removably connected to the second end <NUM> of the third flow path <NUM>.

It will be appreciated that the system <NUM> may include fixed connections between components, but the system <NUM> may be configured for connection to the LOC device <NUM> at the point of use, so removable connections may be provided at least at the second end <NUM> of the first flow path <NUM>, at the second end <NUM> of the second flow path <NUM> and at the second end <NUM> of the third flow path <NUM>, for connection respectively to the LOC device <NUM> first outlet opening <NUM>, second outlet opening <NUM> and inlet opening <NUM>. Alternatively, manufacturers of LOC devices may fixedly connect such devices to the system <NUM>, if desired.

Turning to <FIG>, a second example blood pack donation system <NUM> is configured for use with a LOC device <NUM> for biomarker collection during WB donation. The LOC device <NUM> may be similar to the LOC device <NUM> of the first example. The blood pack donation system <NUM> also preferably is presterilized and configured for use with any of a variety of LOC devices <NUM>, from various manufacturers and for use in separating and screening for collection any of a number of different biomarkers. Accordingly, makers of LOC devices may construct or integrate their LOC devices for use with the system <NUM>.

The second example system <NUM> further includes a fourth flow path <NUM> having a first end <NUM> connected to the first flow path <NUM> at a location between the first end <NUM> and second end <NUM> of the first flow path <NUM> and having a second end <NUM> connected to the third flow path <NUM> at a location between the first end <NUM> and second end <NUM> of the third flow path <NUM>. The connections at the first end <NUM> and second end <NUM> of the fourth flow path <NUM> are shown in <FIG> as Y-connectors <NUM> and <NUM>, but are considered herein to be connections along lengths of the first flow path <NUM> and the third flow path <NUM>. Consistent with the above discussion of the first example system <NUM>, the flow path connections in the second example system <NUM> may be integrated or fixed, or removably connected, and the respective openings in the blood collection container <NUM> and biomarker collection container <NUM> may be preexisting or formed when connected to a respective flow path <NUM>, <NUM>. In addition, the flow paths may be constructed in the form of individual sections of tubing, or may be integrated into a cassette, whether in the form of channels or sections of tubing. As noted with respect to the first example system <NUM>, a further alternative configuration of the second example system <NUM> may be in the form of a cassette, which may provide the respective flow paths already connected to a housing, which may be represented by the body <NUM>, which in turn may accept a LOC device for connection to the respective flow paths for use.

Thus, similarly to the first example system <NUM>, in the second system <NUM> the opening <NUM> of the blood collection container <NUM> may be removably connected to the first end <NUM> of the first flow path <NUM>, and the first outlet opening <NUM> of the LOC device <NUM> may be removably connected to the second end <NUM> of the first flow path <NUM>. Similarly, the opening <NUM> of the biomarker collection container <NUM> may be removably connected to the first end <NUM> of the second flow path <NUM>, and the second outlet opening <NUM> of the LOC device <NUM> may be removably connected to the second end <NUM> of the second flow path <NUM>. In turn, the needle <NUM> may be removably connected to the first end <NUM> of the third flow path <NUM>, and the inlet opening <NUM> of the LOC device <NUM> may be removably connected to the second end <NUM> of the third flow path <NUM>. The first end <NUM> of the fourth flow path <NUM> may be removably connected to the first flow path <NUM> and the second end <NUM> of the fourth flow path <NUM> may be removably connected to the third flow path <NUM>.

As with the previous example, removable connections may be provided in the second example system <NUM> at least at the second end <NUM> of the first flow path <NUM>, at the second end <NUM> of the second flow path <NUM> and at the second end <NUM> of the third flow path <NUM>, for connection respectively to the first outlet opening <NUM>, second outlet opening <NUM> and inlet opening <NUM> of the LOC device <NUM>. Alternatively, manufacturers of LOC devices may fixedly connect such devices to the system <NUM>, if desired.

The second example blood pack donation system <NUM> further includes a plurality of flow control components <NUM>, <NUM> and <NUM> that selectively control flow through the first flow path <NUM>, third flow path <NUM> and fourth flow path <NUM>, respectively. The plurality of flow control components <NUM>, <NUM> and <NUM> that selectively control flow through the first flow path <NUM>, third flow path <NUM> and fourth flow path <NUM> is selectively adjustable for use with a LOC device <NUM> to provide a single pass collection procedure or a multiple pass collection procedure for collecting WB during a WB donation, while also collecting biomarkers.

The second example system <NUM> optionally is capable of use in a multiple pass collection procedure, which includes a succession of adjustments of the plurality of flow control components <NUM>, <NUM> and <NUM>. For example, as shown in <FIG>, the plurality of flow control components <NUM>, <NUM> and <NUM> is adjusted in a first step to permit flow through the first flow path <NUM> to the blood collection container <NUM> and through the third flow path <NUM> to the LOC device <NUM>, while preventing flow through the fourth flow path <NUM>. With such settings of the flow control components, WB may flow through the third flow path <NUM>, the LOC device <NUM>, the first flow path <NUM> to collect WB in the WB collection container <NUM>, while biomarkers flow through the second flow path <NUM> and are collected in the biomarker collection container <NUM>. It will be appreciated that in step one, the flow control component <NUM> may partially or completely close the fourth flow path <NUM>, so as to permit much or most of the WB to flow from the donor D to the blood collection container <NUM>, while a lesser portion of the WB from the donor D must pass through the LOC device <NUM>. This may permit a more rapid procedure, while still providing screening and collection of biomarkers from an adequate portion of the WB donation. Similarly, the flow control component <NUM> optionally may utilize a setting that selectively reduces or increases the flow through the LOC device <NUM>, independently of the WB flow through the fourth flow path <NUM>.

With the system <NUM>, in a second step of a multiple pass collection procedure, the plurality of flow control components <NUM>, <NUM> and <NUM> is further adjustable to permit reverse flow through a first portion 114a of the first flow path <NUM>, through the fourth flow path <NUM> and through and a first portion 130a of the third flow path <NUM>, while preventing reverse flow through a second portion 114b of the first flow path <NUM> and a second portion 130b of the third flow path <NUM>. For example, this may be accomplished if the flow control component <NUM> permits the fourth flow path <NUM> to be partially or fully open, while the flow control components <NUM> and <NUM> fully close the second portion 114b of the first flow path <NUM> and the second portion 130b of the third flow path <NUM>.

To complete the multiple pass collection procedure with the second example system <NUM>, in a third step the plurality of flow control components <NUM>, <NUM> and <NUM> is further adjustable and may be similar to the first step, so as to permit at least some flow through the first flow path <NUM> to the blood collection container <NUM> and through the third flow path <NUM> to the LOC device <NUM>, while partially or fully preventing flow through the fourth flow path <NUM>. Thus, WB may flow through the third flow path <NUM>, the LOC device <NUM>, the first flow path <NUM> to collect WB in the WB collection container <NUM>, while biomarkers flow through the second flow path <NUM> and are collected in the biomarker collection container <NUM>.

It will be appreciated that the plurality of flow control components <NUM>, <NUM> and <NUM> further may include a plurality of respective clamps, such as Roberts-type clamps, pinch, slide or roller clamps, or other suitable types of clamps usable to selectively prevent or permit flow through a flow path that may be a section of tubing or a channel in a cassette or other suitable structure. Accordingly, the plurality of respective clamps <NUM>, <NUM> and <NUM> is adjustable with respect to flow through the first flow path <NUM> to the blood collection container <NUM> and through the third flow path <NUM> to the LOC device <NUM>, as well as the flow through the fourth flow path <NUM>, for use in a single pass collection procedure or optionally in a multiple pass collection procedure.

Consistent with the above description, the system <NUM> may be further adjusted for a second step of a multiple pass collection procedure wherein the plurality of respective clamps <NUM>, <NUM> and <NUM> is further adjustable to permit reverse flow from the blood collection container <NUM> through a first portion 114a of the first flow path <NUM>, through the fourth flow path <NUM> and through a first portion 130a of the third flow path <NUM>, while preventing reverse flow through a second portion 114b of the first flow path <NUM> and a second portion 130b of the third flow path <NUM>.

It will be appreciate that in the second step of the multiple pass collection procedure, to prevent reverse flow through the LOC device <NUM>, one of the respective clamps <NUM> is adjustable to selectively prevent reverse flow through the third flow path <NUM> at a location between the second end <NUM> of the third flow path <NUM> and the connection of the fourth flow path <NUM> to the third flow path <NUM>. A further one of the respective clamps <NUM> is adjustable to selectively prevent reverse flow through the first flow path <NUM> at a location between the second end <NUM> of the first flow path <NUM> and the connection of the fourth flow path <NUM> to the first flow path <NUM>.

Claim 1:
A blood pack donation kit (<NUM>, <NUM>) configured for use in whole blood donation and simultaneous use with a lab-on-a-chip device (<NUM>, <NUM>) for separation and collection of biomarkers, wherein the kit comprises
a) a blood collection container (<NUM>, <NUM>) having a volume and at least one opening (<NUM>, <NUM>);
b) a biomarker collection container (<NUM>, <NUM>) having a volume and at least one opening (<NUM>, <NUM>);
c) a first flow path (<NUM>, <NUM>) having a first end (<NUM>, <NUM>) connected to the opening (<NUM>, <NUM>) in the blood collection container (<NUM>, <NUM>) and a second end (<NUM>, <NUM>) configured to be connected to a first outlet opening (<NUM>, <NUM>) of a lab-on-a-chip device (<NUM>, <NUM>);
d) a second flow path (<NUM>, <NUM>) having a first end (<NUM>, <NUM>) connected to the opening (<NUM>, <NUM>) in the biomarker collection container (<NUM>, <NUM>) and a second end (<NUM>, <NUM>) configured to be connected to a second outlet opening (<NUM>, <NUM>) of the lab-on-a-chip device (<NUM>, <NUM>); and
e) a third flow path (<NUM>, <NUM>) having a first end (<NUM>, <NUM>) connected to a needle (<NUM>, <NUM>) and a second end (<NUM>, <NUM>) configured to be connected to an inlet opening (<NUM>, <NUM>) of the lab-on-a-chip device (<NUM>, <NUM>).