WO2020251431A1

WO2020251431A1 - Method and apparatus for storage of fluid bio-samples in a package

Info

Publication number: WO2020251431A1
Application number: PCT/SE2019/050546
Authority: WO
Inventors: Mikael Löfgren; Maja OLSSON
Original assignee: Miltech Ab
Priority date: 2019-06-11
Filing date: 2019-06-11
Publication date: 2020-12-17

Abstract

The present invention relates to a method for storage of fluid bio- samples. The method involves the steps of providing a package comprising; one or a plurality of cavities, a channel arrangement connecting said one or a plurality of cavities, an inlet port and at least one outlet channel comprising a blocking section allowing for air to escape but not any fluid, filling at least one of said cavities, sealing said inlet port and at least a part of said channel arrangement, storage of said package. Moreover, the present invention also relates to a blister package arrangement for storage of fluid bio-samples. The blister package arrangement comprises a filling cavity connecting to a blister package comprising one or a plurality of cavities, a channel arrangement connecting said one or a plurality of cavities in one or a plurality of sequential lines connecting each of said one or plurality of sequential lines to a blocking section allowing for air to escape but not any fluid.

Description

METHOD AND APPARATUS FOR STORAGE OF FLUID BIO-SAMPLES IN A

PACKAGE

Field of the invention

The present invention relates to an apparatus and a method that will enable storage of fluid bio-samples in a package.

Technical background

In the bio-sector it is common to store fluid bio-samples, for instance blood-samples. The storage of fluid bio-samples could be done with the purpose of later analysis of the sample or some other form of utilization of the sample. During the storing of fluid bio-samples it is of importance that the bio-sample sustains the quality and is easy to handle.

The packaging and storage of fluid in packages is known. One example is shown in W09108951 where there is a blister package having one inlet channel, several connected cavities and from them several channels connected to one single outlet channel is disclosed.

The filling of fluid in packages is known. One example is shown in US2014000223 where there is a method disclosed for filling a cavity of a packaging, particularly a blister packaging. In one embodiment of the method there is disclosed a method for filling an additional cavity, the additional cavity may be attached to the cavity that is to be filled via a supply region and a discharge region, which may be formed in particular by a common channel or separate channels.

Moreover, in US9102463 another method for filling a cavity in a package is disclosed. In this case there is disclosed a method for filling at least one cavity with a liquid by partly filling a cavity of a semi-finished product containing at least two cavities. Further, the semi-finished product is covered, such that the first cavity is completely sealed. Furthermore, the second cavity is filled through displacement of the liquid within the first cavity.

Furthermore, US8563101 discloses a pharmaceutical blister pack for water or water vapor in particular.

The present invention is directed to a method for storage of fluid bio samples. The fluid bio-samples could be of any type such as blood, urine, saliva, sperm, cerebrospinal fluid or any other type of bio-fluid including serum, plasma, cells, DNA, RNA, proteins, lipids or any other type of liquid preparation from bio samples. With bio-samples is also meant samples originating from any domain of eukarya, bacteria or archaea or any combination of those. The fluid bio-samples stored could also be other reagents such as dissolved synthesized DNA, RNA or peptides, with or without chemical modifiers, or any other chemical reagents. The method is especially suitable for use in medical research and diagnostics. The method enables efficient handling, including filling, and long-term storage of the liquid bio-samples. It should be noted that the common feature of the packages and method for filling the same as disclosed above is mainly directed towards filling several cavities with liquid not comprising features within the package allowing for efficient, complete or convenient manual or automated filling.

The problems experienced today relating to storage of fluid bio-samples is that for instance, the process of repeated freezing and then thawing of samples in order to do an analysis, degrades the overall quality of the sample. Thus, preventing researchers from conducting their research in a qualitative manner. Further, many researchers avoid freezing and thawing of samples and instead does aliquoting of the master sample which is a time-consuming process. Another problem that is experienced related to storage and utilization of fluid bio-samples is that due to high volume of storage solutions there can be inconsistency in the freezing process when samples are initially frozen, this may further affect the quality and homogeneity of the sample. Another disadvantage with the existing storage solutions for fluid bio samples is that they can be space inefficient.

The present invention is directed to the purpose of providing an optimized method for storage of fluid bio-samples enabling a space efficient, time efficient and convenient handling for the user.

Summary of the invention

The stated purpose above is achieved by a method for storage of fluid bio-samples comprising the steps of:

• Providing a blister package arrangement comprising a filling cavity, a package and a blocking section for storage of fluid bio-samples, wherein:

o said filling cavity comprising:

^■ an inlet allowing for filling of the cavity before filling of the

package

^■ at least one outlet connecting the filling cavity to a channel

arrangement of said package

o said package comprising: ^■ a blister sheet with a plurality of cavities and a cover sheet

sealing said blister sheet;

^■ a channel arrangement either integrated in said blister sheet or integrated in said cover sheet;

^■ said channel arrangement connecting said filling cavity and

plurality of cavities allowing a fluid to fill at least one of said cavities;

^■ said channel arrangement also connecting said plurality of

cavities in at least one sequential line;

^■ said channel arrangement leading from each at least sequential line separately to a blocking section

o said blocking section allowing air to escape to enable filling of said

sequential line of cavities with a fluid bio-sample but able to block the fluid to allow filling of other parts of the package without letting fluid out.

• Filling at least one of said cavities with a fluid from said filling cavity by said channel arrangement;

• Protecting the fluid filled in the package from further contamination by sealing at least part of said channel arrangement before, between and after said plurality of cavities.

• Storage of at least said package.

Moreover, the present invention also refers to a blister package arrangement comprising a filling cavity, a package and a blocking section for storage of fluid bio-samples, wherein:

• said filling cavity comprising:

o an inlet allowing for filling of the cavity before filling of the package o at least one outlet connecting the filling cavity to a channel arrangement of said package

• said package comprising:

o a blister sheet with a plurality of cavities and a cover sheet sealing said blister sheet;

o a channel arrangement either integrated in said blister sheet or integrated in said cover sheet; o said channel arrangement connecting said filling cavity and plurality of cavities allowing a fluid to fill at least one of said cavities; o said channel arrangement also connecting said plurality of cavities in at least one sequential line;

o said channel arrangement leading from each at least sequential line separately to a blocking section

• said blocking section allowing air to escape to enable filling of said sequential line of cavities with a fluid bio-sample but able to block the fluid to allow filling of other parts of the package without letting fluid out.

The present invention provides a method having several advantages. Firstly, it provides the user with a convenient, space efficient and time efficient method for storage of bio-samples. Since the blister package arrangement contains a channel arrangement that comprises of multiple channels formed in a specific manner connecting the cavities, it makes it possible for the user to divide a master sample creating multiple separate samples with a size appropriate for subsequent analysis, preferably between 5 to 50 pi, in a convenient and efficient way. The channel arrangement allows the plurality of cavities to be partially or fully filled, and the blister package arrangement can further be stored and when needed one or several of the filled cavities with samples can be removed and utilized.

Another important advantage of the present invention is that the blocking section allows for air to escape but not any fluid, this is a problem that for instance US9102463 has not any solution to.

Another important advantage of the present invention is that the channel structure and cavities have a small sectional area perpendicular to the fluid flow during filling with a limited aspect ratio allowing for filling without leaving air bubbles trapped inside of the structure. This sectional area for the cavities is preferably not larger than 20 mm² and not larger than 10 mm² for the channel structure. This leads to another important advantage of the present invention having at least one separate outlet for venting to the blocking section for each sequential line of cavities, as such limited cross sectional area will not allow for complete filling of the cavities utilizing a combined outlet channel for several internal filling channels.

Another important advantage of the present invention is that it allows for extracting a part of the sample without having to affect the remaining sample. Also when stored in freezer a part of the sample can be extracted without the need of thawing even the extracted part of the sample.

When comparing the method according to the present invention with the method disclosed in US2014000223 and US9102463 there are several important differences. First of all, neither US2014000223 or US9102463 is a method directed towards storage of fluid-bio samples. Further, neither of US2014000223 or

US9102463 involve the step of freezing the package in order to enable longer storage.

Several other differences will become evident when viewing the specific embodiments of the present invention.

Further specific embodiments of the invention

Below different embodiments have been disclosed and discussed according to the present invention.

It should be noted that the package is preferably a blister package however, in one specific embodiment, the package is realised as a straw or tube instead of a blister, thus not comprising two separate sheets. In this embodiment the method of filling may include compressing the package during filling resulting in filling the package with less volume than uncompressed. This further allows for creating one or more separate cavities by pressing the walls of the package together at two or more places. Creating cavities may also be allowed by using an expandable enough tube or straw. After creation of the cavities the adjoint walls may be fixed together using e.g. heating, clamping, ultrasonic welding, adhesive, laser welding, or other types of means of sealing a tube. After sealing the tube may also be cut in the clamped section and after cutting be sealed by a cap. Several straws may be put beside each other and assembled to a branching structure allowing to fill several straws from one inlet port or filling them separately. One advantage of this alternative package is that the cavities can be defined and formed after the filling of the package allowing for a more flexible usage.

According to one embodiment of the method, the blister package arrangement is frozen, either prior to storage or post storage. The freezing of the blister package arrangement allows the samples to sustain its quality during the storage process. It should be noted that the freezing of the blister package

arrangement could be done in several different ways, in one embodiment of the method the package is pre-frozen by a cooling element. In another embodiment of the method the package is frozen by being put in a freezer. It should be noted that for space saving or convenience the package within the blister package arrangement could also be separately frozen and handled after removing the filling cavity and/or the blocking section.

According to one specific embodiment of the present invention, the package comprises perforated sections. The perforated sections allow the user to take apart some specific parts of the sample, thus the user doesn’t have to consume the whole sample when only a part of the sample is needed for analysis or another form of utilization.

In a further embodiment, the blister sheet and/or the cover sheet in the blister package arrangement is made of aluminum to allow for cold drawing, forming and sealing the channels, instead of welding. The sheets may also be of a laminated film made of plastics and aluminum allowing for cold drawing but still keeping chemical integrity for the bio-sample. In any embodiment the structures making the channel arrangement and other channels and cavities may be in any sheet, either in the same as the structures for the cavities or in the other or in both.

According to yet another specific embodiment, each perforated section of the package comprises a 1 D or 2D barcode, RFID tag or any other asset tracking technology. It may also be noted that both the whole blister package arrangement as such, as well as the package can contain a specific 1 D or 2D barcode, RFID tag or any other asset tracking technology. This allows the user to firstly easy identify each sample within the package or identify the blister package arrangement or package as such. Further, it also allows the user to save space and time since the blister package arrangement or the package can be stored without the risk of it being mixed with other samples since it can always be identified through the specific code or tag that is assigned to it.

According to yet another specific embodiment such asset tracking technology is arranged protruding outside of the base shape of the blister package arrangement or the package as a tab. This allows for easy identification of the asset tracking technology and readout of the same without the need of removing the blister package arrangement or package from a possible compartment or stack of packages e.g. to identify and find a specific package.

According to yet another specific embodiment, the at least one inlet port has a hydrophilic filter. The hydrophilic filter exhibits an affinity for liquid and therefore it is compatible and optimizes the filling process. The bio-fluid is inserted into the package by appliance of an outside pressure. The outside pressure could be from a syringe, pipette, needle, peristaltic pump or any other device for the filling of an inlet port.

In one specific embodiment the blister package embodiment has a filling cavity and at least one outlet channel leading from the channel arrangement to a blocking section which ensures that the air in the cavities and the channel

arrangement is let out and it further ensures that the fluid is not let out through the blocking section. This is an important feature since it allows the package to be filled by fluid and emptied of air whilst not letting the bio-fluid flow out of the blister package arrangement. In one specific embodiment of the blocking section, the blocking section comprises a hydrophobic filter, this embodiment could be

constructed by using a sheet, or cut parts of sheet, of hydrophobic filter/membrane laminated between parts of the two or more sheets composing the blister package, or prepared by first laminating/welding the membrane onto one or more sheets, before laminating the sheets, or having a hydrophobic filter/membrane affixed into a channel. In one specific embodiment the outlet of the channel arrangement is led to the hydrophobic membrane assuring fluid cannot pass between an outer sheet and the membrane, e.g. by means of welding/gluing/laminating the membrane onto the outer sheet, or welding/gluing/laminating the channel to the membrane.

In one embodiment of the blocking section it contains an air outlet. By blocking this air outlet or applying negative pressure to this air outlet the filling of the individual sequential line(s) of cavities leading to this blocking filter/membrane can be controlled.

In yet another embodiment of the air outlet, it comprises one or more holes through one or more sheets of the package , creating one or more outlets on the surface of the package allowing access to block or to apply negative pressure to this outlet to control the filling of the individual channel(s) leading to this blocking filter/membrane can be controlled.

The blocking section could utilize a fluid sensor, e.g. capacitive, magnetic, optical, thermal, that can determine whether there is fluid at the sensor placed in a filling/sealing machine to sense if there is fluid inside of the package at a specific position such as any cavity, part of the channel arrangement, the filling cavity or the blocking section. The blocking section could control the filling of the blister package arrangement based on the fluid sensor output.

In yet another specific embodiment the blocking section as such is constructed to detain fluid, allowing the outlet channel to only let out air and not fluid. This can be achieved by having a narrow and/or long channel structure where the channel length typically is at least 10 times its width, and its smallest width is typically less than 0.5 mm and the channel area typically is less than 0.25 mm ².

In yet another specific embodiment the at least one part of the blocking section is used by two or more channels meeting the common blocking section at different locations, having one separate outlet channel and its separate connection with the blocking section for each of the series of one or more cavities the outlet channel is connected to.

In yet another specific embodiment the at least one blocking section is connected to at least one outlet channel. One specific embodiment having one or several blocking sections connected to at least one outlet channel by channels. The blocking section may also be used on the first proposed embodiment where the package is realised as a straw or tube instead of a blister.

The blocking section can in a specific embodiment have several filter types combined.

In one embodiment, there is a larger open filling cavity integrated or assembled to the blister holding the full amount of sample. The sample can then be dispensed into this filling cavity for allowing the blister to be filled from this cavity by a tool or machine exercising pressure onto the cavity or vacuum onto the blocking section. The opening of this filling cavity may be as large as the cavity or only as large as required to allow for filling with a suitable tool holding or leading the fluid.

In a further embodiment the blister package arrangement is provided with an integrated filling tube connected with the blister package arrangement by means of a flexible tubing. The sample can then be dispensed in this filling tube and the blister package arrangement may be filled either by pressing the sample, e.g. using a piston or external air pressure, or by means of a peristaltic pump working on the connecting tubing.

According to yet another specific embodiment, the cavities are placed non-symmetric in relation to the center of the package, in a way so that two packages can be placed with the blister sheets facing towards each other without the cavities meeting. This allows for a much denser packaging also with some distance between the cavities.

According to yet another specific embodiment of the package, there is provided at least one integrated means of bending in an angle, bend indication, created by e.g. bending, heat forming, perforation or other method. Preferably it has two parallel such bend indications centered or aligned, dividing the sheet in three flat parts. One narrow in between two wider parts, the narrow defining the resulting distance between the two wider after bending the sheet 90 degrees at each bend indication. The distance allowing the protruding parts of the cavities fit between the two parallel sheet parts. As an alternative one bend at 180 degrees, with a radius of half the distance of the parallel sheet parts can be used, or a higher number of bend indications each bend in 90 degrees or less, as long as the result is two mainly parallel sheets with cavities. In a preferred embodiment of this bend package the cavities are arranged so they do not meet each other after the blister package has been bend. This allows for a denser packaging and a lower thickness of the bend package.

According to yet another specific embodiment, the channel arrangement is connected to the filling cavity and is divided perpendicular in relation to the axis of the filling cavity in two channel sections, wherein each channel section is branched in at least one branch section, wherein each branch section extends parallel to the axis of the filling cavity, wherein each branch section connects said plurality of cavities in each section, wherein each branch section comprises one outlet channel. This construction allows for the package to fast and efficiently lead out any air that resides in the package. In this construction where each line of sequential cavities in the branch section has its own outlet channel which also makes the filling process faster.

The channel arrangement is connected to the filling cavity and is divided perpendicular in relation to the filling cavity in two channel sections, wherein each channel section is branched in at least one branch section, wherein each branch section extends parallel away from the filling cavity, wherein each branch section connects said plurality of cavities in each section.

The sealing of at least part of the channel arrangement before, between and after said plurality of cavities could be done in several different ways. The sealing process is an important aspect of the method since if any cavity or channel is left open there will be risk for the sample to be contaminated or for parts of the sample to escape from the cavity. Further, unsealed parts can also create leakage which for instance lead to the cavities in the sample having too little bio-fluid left in order for the user to be able to utilize. Leakage can also contaminate people and/or utensils and/or surfaces and/or other samples directly or indirectly creating both personal hazard and invalidating other analysis. In one specific embodiment of the invention the sealing of the package is done through heating, compression or welding. It should be noted that there are several different welding techniques that could be utilized in this method such as pattern welding, heat welding, ultrasonic welding or high frequency welding.

The channels and cavities may have a small sectional area perpendicular to the fluid flow during filling with a limited aspect ratio allowing for filling without leaving air bubbles trapped inside of the structure. The cross-sectional area of a channel is preferably less than 10 mm2, and the cross sectional area of a cavity is preferably less than 20 mm2, where the aspect ratio between width and height (the largest of width/height and height/width) preferably is less than 4.

When the package or cavity has been frozen and the user wants to withdraw fluid from a sample, they could do this in several different ways. If the package or cavity is still frozen then according to one specific embodiment of the method the user can pop the frozen pellets out from the blister sheet with or without the help of a tool. It should be noted that in some cases the bio-fluid in the package or cavity has been thawed then there are different alternatives on how to withdraw the thawed bio-fluid. The user may also use an auxiliary tool can make a hole in the cover and suck the bio-fluid out. Another variation to withdraw fluid is to use a punch is for making a hole in the cover, allowing the bio-fluid to flow into a container.

According to one embodiment of the sheets in the package, one or both sheets comprise a hard or stiff material such as thicker plastics or aluminum and an inner layer of softer or thinner plastics that will protect the bio-sample from outside contamination as the sample is pressed through the layered sheet. Using this embodiment, the harder or thicker layer may also be pre-cut to assist the extraction of the bio-sample, while an inner or outer softer or thinner layer assures chemical integrity and protects the sample from contamination.

According to one embodiment the sample volume to be filled is known or can be measured e.g. by means of user input or weighing. Then parts of the channel arrangement can be blocked, either by blocking one or more channels, or by blocking one or more outlets, and by such control which cavities to be filled, ensuring specific and designated (consecutive and/or parallel) cavities are fully filled when the available sample volume is less than the total volume that can be contained within the package.

In one specific embodiment the package is filled in sections by controlling blockage of channels and/or outlets, assuring that designated parts of the package are fully filled before others. This allows for controlled filling of the package when available sample is less that available storage volume within the package, even without prior knowledge of the available sample volume.

It should be noted that the different embodiments presented in this section all may be combined with one another in different ways. It will be appreciated by a person skilled in the art that numerous variations and/or modifications may be made to the present invention as shown in the specific embodiments without departing from the scope of the invention as broadly described, the present embodiments are, therefore, to be considered in all respects to be illustrative and not restrictive.

According to one specific embodiment of the present invention the fluid is filled into said filling cavity by gravity, using e.g. a pipette, a tube or a syringe to guide and fill the fluid into said filling cavity.

According to another specific embodiment of the present invention said blocking section is controlled by controlling the pressure inside of said blocking section and wherein this control of pressure is controlled dependent on

measurements of whether either said cavities, parts of said channel arrangement or the blocking section contain air or fluid. This measurement can be performed by means of optical, capacitive, magnetic, thermal, or sonic sensors.

According to one yet another specific embodiment of the present invention one or more of said cavities are extracted from said package, by means of e.g. cutting or tearing, without compromising the integrity of the stored sample within e.g. by thawing if already frozen or by opening the package towards any sample thus risking to contaminate either the sample or the surroundings. This allows for keeping the integrity of all of the sample, the remaining as well as the extracted, up to analysis, as necessary.

Moreover, according to one specific embodiment of the present invention subsequent removal of one or more of said cavities is facilitated by perforation of the package. It can also be facilitated by marking the package making it easy for the right placement of e.g. a cutter, either controlled manually or automatically, also without perforation.

According to another specific embodiment of the present invention said package and each of said cavities comprises a 1 D or 2D barcode, RFID tag or any other asset tracking technology allowing for tracking and identification of both a fluid sample post removal of such cavity from the package as well as said package as such. Especially when such asset tracking technology of said package is placed on a tab protruding outside of the base structure of the package to further facilitate both automated and manual tracking and identification post storage.

Moreover, according to one embodiment, said filling cavity, said blocking section, or both said filling cavity and said blocking section are integrated into the same package. Furthermore, according to one specific embodiment of the present invention several parts of the blister package arrangement are manufactured together with the package being manufactured as one integral part out of the same blister sheet construction. In one specific embodiment the filling cavity and the package are integrated, and in another specific embodiment the package and the blocking section are integrated, and in one third specific embodiment the complete blister package arrangement is manufactured as a blister package integrating both the filling cavity, the package and the blocking section.

According to yet another specific embodiment of the present invention the inlet of the filling cavity is arranged to allow for dispensing a fluid into said filling cavity by gravity, e.g. using a pipette or other means of leading the fluid to flow or drip into the filling cavity. This allows for efficient both manual and automatic handling and filling using both the existent tools and infrastructure as well as current methods for handling the samples. This can be achieved by allowing said inlet being larger than said means of leading the fluid into the filling cavity, or larger than the droplets or water jet if poured.

According to one specific embodiment of the present invention at least part of said channel arrangement is arranged to be sealed after filling of said package to protect any fluid that is filled in said plurality of cavities.

Moreover, according to another specific embodiment of the present invention the filling cavity and the blocking section is removed from the blister package arrangement after filling and sealing for space efficient storage of the package. This can also be done when the blister package arrangement is fully integrated and then removing may be facilitated e.g. by previous perforation of the blister package arrangement. The blister package arrangement may also be designed to facilitate cutting after the filling and sealing process, and still keep sample integrity and protecting the package from contamination.

According to yet another specific embodiment of the present invention the package comprises perforated sections to facilitate for removal of at least one of said plurality of cavities by hand or using a simple tool. It is especially preferred that the outer rim of the package is intact and only internal sections are removed, to allow for subsequent unmodified storage for and handling of the package. The perforations may allow only for single cavities to be removed separately, or for a row or column of cavities to be removed, or a matrix of cavities to be removed dependent on how these perforations have been designed.

Moreover, according to one specific embodiment of the present invention for each of said cavities there is also a 1 D or 2D barcode, RFID tag or any other asset tracking technology allowing for tracking and identification of a fluid sample post removal of such cavity from the package. In a further development of the method this will allow for extraction of several samples, also from different packages (even still frozen), in a same compartment, and subsequent automated sorting and extraction of these samples prior to analysis.

Furthermore, according to one specific embodiment of the present invention said package comprises a 1 D or 2D barcode, RFID tag or any other asset tracking technology allowing for identification, preferably wherein said asset tracking technology protrudes outside of the base shape of said package as a tab, allowing for identification without extracting said package from a storage compartment or a stack or a collection of such packages. This tab can be integral to the blister package during production or added as a separate means of identification up to the filling of said package.

According to one specific embodiment of the present invention said blocking section comprises a hydrophobic membrane allowing for air to pass but not fluid.

According to yet another specific embodiment of the present invention said blocking section is realised by controlling the pressure inside of the blocking section, such as wherein said control of the pressure inside of the blocking section is realised by applying a pressure and/or vacuum to the outlet of the blocking section or such as wherein said control of the pressure inside of the blocking section is controlled by measuring the presence or absence of fluid within a cavity, part of channel arrangement or a blocking section.

Detailed description of the drawings

FIG 1. Shows a perspective view of one embodiment of the blister package arrangement 100 standing according to the present invention. As seen the blister package arrangement 100 comprises one filling cavity 1 followed by a package 2 and a blocking section 3. The filling cavity 1 comprising an inlet 7 allowing for gravity filling of said filling cavity 1 and an outlet 8 connected to the channel arrangement 5 of the following package 2. The package 2 comprising one blister sheet 11 comprising a plurality of cavities 4 and behind said blister sheet 11 a cover sheet 12 in this embodiment comprising said channel arrangement 5 connecting said cavities 4 in several sequential lines of cavities 6, further separately connecting these several lines of cavities 6 to a blocking section 3 comprised in the blister package arrangement. In this embodiment each line of cavities 6 is thus individually controlled by a separate part of the blocking section 3 allowing for control by e.g. an internal hydrophobic filter or individual external pressures applied to the outlets of the blocking section.

FIG 2. Shows two views of the blister package in the embodiment of FIG 1 , the first one with the cover sheet 12 exploded behind the blister sheet 11 to show the channel arrangement 5 on the cover sheet 12 and the plurality of cavities 4 on the blister sheet 11 , and the second from the cover sheet 12 side thus only showing the channel arrangement 5.

FIG 3. Shows a perspective view of one embodiment of the blister package arrangement 100 where both the filling cavity 1 , the package 2 and the blocking section 3 are integrated into the same blister package. It also shows the channel arrangement 5 on the same blister sheet as the plurality of cavities 4.

FIG 4. Shows the same specific embodiment as FIG 3, but after compressing or welding part of the channel arrangement 5 to protect the sample filled in the plurality of cavities 4.

FIG 5. Shows the same specific embodiment as FIG 4, but after cutting the inlet cavity 1 and the blocking section 3 from the blister package arrangement 100 leaving only an optimized package 2 for further storage of the sample. It also shows a flat view of one embodiment of the blister package showing the cavities 4 within perforated sections 9 and both the package 2 having a tab with asset tracking technology as well as the cavities having asset tracking technology 10 attached.

Claims

1. A method for storage of fluid bio-samples comprising the steps of:

• Providing a blister package arrangement (100) comprising a filling cavity (1 ), a package (2) and a blocking section (3) for storage of fluid bio-samples, wherein:

o said filling cavity (1 ) comprising:

^■ an inlet (7) allowing for filling of the cavity (1 ) before filling of the package (2)

^■ at least one outlet (8) connecting the filling cavity to a channel arrangement (5) of said package (2)

o said package (2) comprising:

^■ a blister sheet (1 1 ) with a plurality of cavities (4) and a cover sheet (12) sealing said blister sheet (1 1 );

^■ a channel arrangement (5) either integrated in said blister sheet (1 1 ) or integrated in said cover sheet (12);

^■ said channel arrangement (5) connecting said filling cavity (1 ) and plurality of cavities (4) allowing a fluid to fill at least one of said cavities (4);

^■ said channel arrangement (5) also connecting said plurality of cavities (4) in at least one sequential line (6);

^■ said channel arrangement (5) leading from each at least

sequential line (6) separately to a blocking section (3) o said blocking section (3) allowing air to escape to enable filling of said sequential line of cavities (6) with a fluid bio-sample but able to block the fluid to allow filling of other parts of the package without letting fluid out.

• Filling at least one of said cavities (4) with a fluid from said filling cavity (1 ) by said channel arrangement (5);

• Protecting the fluid filled in the package from further contamination by sealing at least part of said channel arrangement (5) before, between and after said plurality of cavities (4).

• Storage of at least said package (2).

2. The method according to claim 1 , wherein said sealing for protection of the fluid filled in the package is performed through heating, compression or welding, and where said sealing is preceded by pressing the channels, allowing for removal and protection of the bio-fluid before sealing.

3. The method according to claim 1 or 2, wherein the fluid is filled into said filling cavity (1 ) by gravity, using e.g. a pipette, a tube or a syringe to guide and fill the fluid into said filling cavity (1 ).

4. The method according to any of claims 1 -3, wherein said plurality of cavities (4) and said channel arrangement (5) having a small enough cross sectional area, not allowing a leading gas/fluid frontier to divide, thus assuring that no air is left trapped inside of said plurality of cavities (4) or said channel arrangement (5) after filling.

5. The method according to any of claims 1 -4, wherein said blocking section (3) comprises a membrane, this membrane being a hydrophobic membrane, thus allowing air to pass but not fluid.

6. The method according to any of claims 1 -5, wherein said blocking section (3) is controlled by controlling the pressure inside of said blocking section and wherein this control of pressure is controlled dependent on measurements of whether either said cavities (3), parts of said channel arrangement (5) or the blocking section contain air or fluid, wherein this measurement may be performed by means of optical, capacitive, magnetic, thermal, or sonic sensors.

7. The method according to any of claims 1 -6, wherein the package (2) is frozen prior to or post-storage.

8. The method according to any of claims 1 -7, wherein one or more of said cavities (4) are extracted from said package (2), by means of e.g. cutting or tearing, without compromising the integrity of the stored sample within e.g. by thawing if already frozen or by opening the package towards any sample thus risking to contaminate either the sample or the surroundings.

9. The method according to any of claims 1 -8, wherein subsequent removal of one or more of said cavities is facilitated by perforation of the package creating perforated sections (9).

10. The method according to any of claims 1-9, where to said package (2) and where to each of said cavities (4) a 1 D or 2D barcode, RFID tag or any other asset tracking technology (10) is added allowing for tracking and identification of both a fluid sample post removal of such cavity (4) from the package as well as said package (2) as such. Especially when such asset tracking technology (10) of said package (2) is placed on a tab protruding outside of the base structure of the package to further facilitate both automated and manual tracking and identification post storage.

11. A blister package arrangement (100) comprising a filling cavity (1 ), a package (2) and a blocking section (3) for storage of fluid bio-samples, wherein:

• said filling cavity (1 ) comprising:

o an inlet (7) allowing for filling of the cavity (1 ) before filling of the package (2)

o at least one outlet (8) connecting the filling cavity to a channel arrangement (5) of said package (2)

• said package (2) comprising:

o a blister sheet (11 ) with a plurality of cavities (4) and a cover sheet (12) sealing said blister sheet (11 );

o a channel arrangement (5) either integrated in said blister sheet (11 ) or integrated in said cover sheet (12);

o said channel arrangement (5) connecting said filling cavity (1 ) and

plurality of cavities (4) allowing a fluid to fill at least one of said cavities (4);

o said channel arrangement (5) also connecting said plurality of cavities (4) in at least one sequential line (6);

o said channel arrangement (5) leading from each at least sequential line (6) separately to a blocking section (3) • said blocking section (3) allowing air to escape to enable filling of said sequential line of cavities (6) with a fluid bio-sample but able to block the fluid to allow filling of other parts of the package without letting fluid out.

12. The blister package arrangement (100) according to claim 11 , in which said filling cavity (1 ), said blocking section (3), or both said filling cavity (1 ) and said blocking section (3) are integrated into the same package.

13. The blister package arrangement (100) according to claim 11 or 12, wherein the inlet (7) is arranged to allow for dispensing a fluid into said filling cavity (1 ) by gravity, e.g. using a pipette or other means of pouring or dripping.

14. The blister package arrangement (100) according to any of claims 11 -13, wherein at least part of said channel arrangement (5) is arranged to be sealed after filling of said package (2) to protect any fluid that is filled in said plurality of cavities (4).

15. The blister package arrangement (100) according to any of claims 11 -14, wherein said filling cavity (1 ) and said blocking section (3) is removed after filling and sealing for space efficient storage of the package (2).

16. The blister package arrangement (100) according to any of claims 11 -15, wherein the package (2) comprises perforated sections (9) to facilitate removal of at least one of said plurality of cavities (4) by hand or using a simple tool.

17. The blister package arrangement (100) according to any of claims 11 -16, wherein for each of said cavities (4) there is also a 1 D or 2D barcode, RFID tag or any other asset tracking technology (10) allowing for tracking and identification of a fluid sample post removal of such cavity (4) from the package.

18. The blister package arrangement (100) according to any of claims 11 -17, wherein said package (2) comprises a 1 D or 2D barcode, RFID tag or any other asset tracking technology (10) allowing for identification, preferably wherein said asset tracking technology (10) protrudes outside of the base shape of said package (2) as a tab, allowing for identification without extracting said package (2) from a storage compartment or a stack or a collection of such packages.

19. The blister package arrangement (100) according to any of the claims 11 -18, wherein said blocking section (3) comprises a hydrophobic membrane allowing for air to pass but not fluid.

20. The blister package arrangement (100) according to any of claims 11 -19, wherein said blocking section (3) is realised by controlling the pressure inside of the blocking section, such as wherein said control of the pressure inside of the blocking section (3) is realised by applying a pressure and/or vacuum to the outlet of the blocking section (3) or such as wherein said control of the pressure inside of the blocking section (3) is controlled by measuring the presence or absence of fluid within a cavity, part of channel arrangement or a blocking section.