# US 10,767,146 B2 · Blood culture bottles with mechanisms for controlled release of substances into culture media

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- Number: US 10,767,146 B2
- Document ID: US10767146B2
- Status: Granted
- Kind: B2
- Application number: 15/031,958
- Filed: 2014-10-24
- Published: 2016-09-15
- Granted: 2020-09-08
- Earliest claimed: 2013-10-25
- Assignees: Becton, Dickinson and Company
- Applicants: Becton, Dickinson and Company
- Inventors: Mei Yang-Woytowitz; Brent Pohl; Gary F. Hershner; Eric Ursprung; Michael A. Brasch; Ming-hsiung Yeh; Patrick Shawn Beaty; Charles C. Yu; Timothy M. Wiles; Liping Feng; Ben Turng; Xiaofei Chang; Patrick R. Murray
- Web page: https://patentgrep.com/patent/US10767146B2

## CPC

- C12Q 1/02: involving viable microorganisms
- A61J 1/05: for collecting, storing or administering blood, plasma or medical fluids {(multiple bags systems for separating or storing blood components A61M1/0209); Infusion or perfusion containers}
- A61J 1/1406: {Septums, pierceable membranes}
- A61J 1/1418: {Threaded type}
- A61J 1/2006: {Piercing means}
- A61J 1/2089: {Containers or vials which are to be joined to each other in order to mix their contents (combinations of vial and syringe for mixing their contents A61J1/2096)}
- A61J 1/2093: {Containers having several compartments for products to be mixed}
- B01L 3/502: {with fluid transport, e.g. in multi-compartment structures}
- C12C 1/02: Pretreatment of grains, e.g. washing, steeping
- C12M 23/08: {Flask, bottle or test tube}
- C12M 23/38: {Caps; Covers; Plugs; Pouring means}
- C12M 29/00: {Means for introduction, extraction or recirculation of materials, e.g. pumps (pumps per se F04B)}
- B01L 2200/0621: Control of the sequence of chambers filled or emptied
- B01L 2200/16: Reagents, handling or storing thereof
- B01L 2300/044: pierceable, e.g. films, membranes
- B01L 2300/047: Additional chamber, reservoir
- B01L 2300/0832: cylindrical, tube shaped
- B01L 2300/087: Multiple sequential chambers
- G01N 2800/26: Infectious diseases, e.g. generalised sepsis
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- A61J: CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- C12C: BEER; PREPARATION OF BEER BY FERMENTATION (ageing or ripening by storing C12H1/22; methods for reducing the alcohol content after fermentation C12H3/00; methods for increasing the alcohol content after fermentation C12H6/00; venting devices for casks, barrels or the like C12L9/00); PREPARATION OF MALT FOR MAKING BEER; PREPARATION OF HOPS FOR MAKING BEER
- C12M: APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; {APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS}
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

An apparatus and associated methods of use for a controlled combination of reagents is disclosed. The apparatus includes a vessel 400, a vessel insert 220, and a cap element 200. The vessel 400 has a body portion 410 for receiving a biological sample. The vessel insert 220 receives at least one reagent therein. Preferably, the vessel insert 220 is received in a portion 420 of the vessel 400. The cap element 200 is attached to the vessel 400 to secure the vessel insert 220 in the vessel 400. During use, the vessel insert 220 is adapted to release its contents when the biological sample is introduced into the body portion 410 of the vessel 400 upon application of an intermixing force to the vessel insert 220. A variety of intermixing forces may be applied, depending upon the embodiment of the present invention and its associated methods of use.

## Claims

### Claim 1

An apparatus for a controlled combination of reagents, the apparatus comprising:
a vessel adapted for receiving a biological sample having a neck portion and a body portion wherein the body portion of the vessel contains a culture media prior to receiving the biological sample and wherein the body portion of the vessel comprises one or more sensors for monitoring conditions in the culture media or a headspace gas in the vessel;
a cap element attached to the vessel;
a vessel insert secured in the neck portion of the vessel by the cap element and adapted for receiving at least one reagent wherein the at least one reagent is selected from the group consisting of adsorption resin, culture medium, lytic reagent, and a combination thereof, wherein the culture media is a lytic media adapted to grow microorganisms therein, the microorganisms selected from the group consisting of aerobic microorganisms, anaerobic microorganisms, mycobacteria, fungi, and yeast and wherein the culture media is in liquid or lyophilized form;
wherein the cap element further comprises a pierceable aperture through which is received the biological sample into the vessel or vessel insert;
at least one sealing element separating the at least one reagent received by the vessel insert from the body portion of the vessel, and
a rod having a proximal end and a distal end positioned within the vessel so that the proximal end is adjacent to the cap element and distal end is in a first position proximal to the at least one sealing element; and
wherein force applied to the proximal end of the rod results in the distal end of the rod moving from the first position to a second position thereby disrupting the at least one sealing element to allow contents of the vessel insert to release into the body portion of the vessel, and wherein the apparatus is operable to initiate disruption separately from and after receiving of the biological sample via the pierceable aperture into the vessel or vessel insert.

### Claim 2 (depends on 1)

The apparatus of claim 1, wherein the vessel insert is tubular-shaped and wherein the distal end of the rod is tapered.

### Claim 3 (depends on 2)

The apparatus of claim 2, wherein the force is applied either automatically or manually to the proximal end of the tapered rod, and wherein the distal end of the tapered rod pierces the vessel insert thereby disrupting the at least one sealing element and releasing the contents of the vessel insert into the body portion of the vessel wherein the vessel insert is sealed by the at least one sealing element, and wherein the tapered rod pierces the at least one sealing element.

### Claim 4 (depends on 3)

The apparatus of claim 3, wherein the cap element is threaded onto the neck portion of the vessel and twisting the cap element downward onto the neck portion of the vessel causes the tapered rod to advance and pierce the at least one sealing element thereby disrupting the vessel insert and releasing the contents of the vessel insert into the body portion of the vessel.

### Claim 5 (depends on 1)

The apparatus of claim 1, wherein the vessel insert comprises a tubular body having a constant diameter extending into the neck portion of the vessel and the rod has an elastomeric seal at each end that is adapted to seal the tubular bodied vessel insert, wherein advancing the rod distally within the tubular vessel insert disrupts the sealing element thereby releasing the contents of the vessel insert into the body portion of the vessel.

### Claim 6 (depends on 1)

The apparatus of claim 1, wherein the pierceable aperture of the cap element is a resealable septum portion and is adapted to seal the vessel and secure the vessel insert in the vessel.

### Claim 7 (depends on 1)

The apparatus of claim 1, wherein a proximal end of the vessel insert comprises an annular ring and the sealing element, wherein the cap element comprises a deformable flange with an internal opening, the deformable flange being adapted to secure the vessel insert in the vessel when the annular ring is located adjacent to the internal opening, and wherein disrupting the sealing element also advances the annular ring through the deformable flange thereby releasing the contents of the vessel insert into the body portion of the vessel wherein the deformable flange is elastomeric, and wherein a distal surface of the deformable flange is angled to seal the vessel upon reducing the a pressure in the vessel insert to less than atmospheric pressure.

### Claim 8 (depends on 2)

The apparatus of claim 2, wherein the vessel insert defines an internal chamber within the neck portion of the vessel for receiving the reagent, the internal chamber having a floor with a raised central portion extending proximally from the floor to a proximal portion comprising the at least one sealing element thereby defining a tube, wherein disrupting the at least one sealing element allows the release of the contents of the vessel insert into the body portion of the vessel and wherein a portion of the floor is thinner than a remainder of the vessel insert, and wherein disrupting the at least one sealing element and causes the raised central portion to break off and separate from the vessel insert.

### Claim 9 (depends on 1)

The apparatus of claim 1, wherein a proximal end of the vessel insert comprises at least one opening and the at least one sealing element, the at least one sealing element being adapted to seal a body portion of the vessel insert, the opening allowing for fluid communication with the body portion of the vessel wherein sample is introduced into the body portion of the vessel through the opening, wherein the cap element comprises a cap and a septum, the cap being adapted to secure the vessel insert and the septum to the proximal end of the vessel, and wherein disrupting the at least one sealing element places the vessel insert in fluid communication with the body portion of the vessel and wherein the at least one opening is located between the proximal end of the vessel and the at least one sealing element.

### Claim 10 (depends on 1)

The apparatus of claim 1, wherein the vessel insert has a head portion and a body portion, the head portion having a surface sized to rest upon a proximal end of the vessel to support the vessel insert in the vessel, the at least one sealing element located distally from the proximal end of the vessel, wherein the cap element comprises a cap and a septum, the cap being adapted to secure the vessel insert and the septum to the proximal end of the vessel, and wherein disrupting the at least one sealing element releases the contents of the vessel insert into the body portion of the vessel.

### Claim 11 (depends on 1)

The apparatus of claim 1, wherein the biological sample is a sterile body fluid and the sterile body fluid is introduced into the vessel by a sample delivery device comprising a cannula within a needle through which the sterile body fluid flows from the sample delivery device.

### Claim 12 (depends on 3)

The apparatus of claim 3, wherein the at least one sealing element is made of at least one thin material selected from a group consisting of foil, glass, molded polymer, and a combination thereof.

### Claim 13 (depends on 12)

The apparatus of claim 12, wherein the at least one sealing element is a membrane having a sealed interior cavity filled with carbon, glass or at least one reagent.

### Claim 14 (depends on 13)

The apparatus of claim 13, wherein the at least one reagent is selected from the group consisting of adsorption resin, culture medium, lytic reagent, and a combination thereof.

### Claim 15 (depends on 1)

A method of operating the apparatus of claim 1, comprising the steps of:
obtaining the apparatus of claim 1 and
introducing the biological sample into the vessel through the cap element;
wherein after introduction of the biological sample, the rod is operated so as to disrupt a portion of the vessel insert and release of the contents of the vessel insert into the body portion of the vessel containing the culture media thereby combining the at least one reagent, the biological sample and the culture media in the vessel.

### Claim 16 (depends on 8)

The apparatus of claim 8, wherein the internal chamber of the vessel insert contains the at least one reagent; and the body portion of the vessel contains a culture media; wherein when a force is applied to the proximal sealing element so as to disrupt the proximal sealing element thereby disrupting the vessel insert; and wherein, after the vessel insert is disrupted, the vessel is tilted to release the contents of the internal chamber into the body portion of the vessel.

### Claim 17 (depends on 1)

The apparatus of claim 1, wherein the vessel insert comprises a tubular body and a stopper secured to the tubular body by a vacuum force, wherein the tubular body of the vessel insert contains the at least one reagent and a pressure in the vessel insert is less than atmospheric pressure; and further wherein after the biological sample is introduced into the vessel insert through the cap, the rod disrupts the seal and vacuum force so as to detach the stopper and release the contents of the vessel insert into the body portion of the vessel.