METHODS AND SYSTEMS FOR ADJUSTING THE pH OF MEDICAL BUFFERING SOLUTIONS
Buffer solutions within a plurality of containers can be adjusted and controlled by exposing the containers while open to a controlled environment. In particular, an inventory of containers holding bicarbonate buffers can be adjusted to a precisely controlled pH by exposing the containers while open to a controlled carbon dioxide environment in a treatment chamber.
1 . A method for adjusting pH in a plurality of buffer containers, said method comprising:
positioning each of the containers in a chamber with the container open to expose the buffer to an atmosphere in the chamber;
controlling the pressure, temperature, and CO 2 level of the atmosphere to values selected to provide a target equilibrium pH of the buffer;
holding the containers in the controlled atmosphere of the chamber for a time sufficient for the buffer in each of the containers to reach the target pH; and
sealing each of the containers to inhibit changes in pH over time.
2 . A method as in claim 1 , further comprising moving the containers within the chamber to promote mixing of the atmosphere and mixing of the buffer solution.
3 . A method as in claim 1 , wherein controlling the pressure, temperature, and CO 2 level of the atmosphere comprises introducing, circulating, and removing gas from the chamber.
4 . A method as in claim 3 , wherein the gas is introduced and removed at a substantially constant flow rate.
5 . A method as in claim 4 , wherein the flow rate is in the range from 0.1V to 1V per hour, where V is the open internal volume of the chamber.
6 . A method as in claim 1 , wherein the open containers are held in the chamber for at least 24 hours.
7 . A method as in claim 6 , wherein the open containers are held in the chamber for a time in the range from 24 hours to 96 hours.
8 . A method as in claim 1 , wherein the temperature is in the range from 70° C. to 74° C., the pressure is with 1% of atmospheric, and the CO 2 content is at least 97% by volume, providing a pH in the range from 7.63 to 7.75
9 . A method as in claim 1 , wherein the gas has a 100% relative humidity when introduced to the chamber.
10 . A method as in claim 1 , wherein at least some of the containers include a volume of water which evaporates during the period of time when the container is held in the chamber to raise the relative humidity within the chamber.
11 . A method as in claim 1 , wherein the container is sealed with no headspace remaining after sealing.
12 . A method as in claim 11 , wherein the container is entirely filled while in the chamber.
13 . A method as in claim 11 , wherein the container is partially filled to increase the available open surface area while in the chamber and completely filled prior to sealing.
14 . A method as in claim 13 , wherein the container is completely filled by reducing the volume within the container.
15 . A method as in claim 1 , wherein all containers are identical in shape and volume.
16 . A method as in claim 1 , wherein the containers are sealed while within the chamber.
17 . A method as in claim 1 , wherein the containers are removed from the chamber and then sealed.
18 . A system for adjusting the pH of a plurality of buffer containers, said system comprising:
a chamber having a perimeter wall and an interior;
a gas supply connected to deliver a gas flow into the interior of the chamber, wherein the gas flow comprises at least about 97% by volume carbon dioxide;
a plurality of spaced-apart supports within the interior of the chamber; and
a multiplicity of pneumostatic passages formed through the perimeter wall and located to allow buffer containers to be placed on and removed from each of the supports.
19 . A system as in claim 18 , wherein the chamber comprises a free-standing cabinet.
20 . A system as in claim 18 , wherein a mechanism imparts vibration to the containers, which causes the contents of the container to mix during pH adjustment.
21 . A system as in claim 18 , further comprising a water bath which receives and humidifies the gas flow.
22 . A system as in claim 18 , wherein the supports are present on a rotatable carousel present within the chamber.
23 . A system as in claim 22 , wherein the carousel comprises a plurality of stacked, circular shelves.
24 . An inventory of buffer containers comprising:
a plurality of containers filled with an aqueous solution of a sodium bicarbonate solution, wherein each container in the inventory has:
a volume of sodium bicarbonate solution in the range from 1.0 ml to 50.0 ml; and
a pH variation below ±0.05 when compared to the pH of all other containers in the inventory.
25 . An inventory as in claim 24 , wherein the sodium bicarbonate solution in each container is maintained at a pressure above atmospheric to inhibit the evolution of carbon dioxide during storage.
26 . An inventory as in claim 25 , wherein each container has an open interior filled with the sodium bicarbonate solution, a needle-penetrable septum, a plunger, and a compression member which exerts a force on the plunger which is sufficient to pressurize the sodium bicarbonate solution and inhibit the evolution of carbon dioxide.
27 . An inventory as in claim 24 , further comprising a box which holds the plurality of containers.