Field of the Invention

The present invention relates to a system and method for mixing two or more solutions or buffers. More specifically, the invention provided a system that contains a flexible mixer chamber the volume of which is adjusted in response to an input flow rate, as well as method of using the system to achieve homogeneous mixing of two or more buffers. Background of the Invention

Many biological and chemical applications require instant mixing of two or more buffers to generate a suitable solution. Normally different buffers are mixed in a mixer chamber, and transferred to one or more reaction containers after mixing. The ratio of input buffers is generally controlled by adjusting the incoming flow rate of the buffers.

While mixing of buffers is a somewhat standard process, current systems are incapable of offering a flexible solution. When the experimental needs call for a small amount of a solution, a small mixer chamber is desirable than a larger one, to reduce dead volume, it is also more cost effective since it reduces buffer waste. On the other hand, when a large amount of solution is needed, a small chamber would not be able to fulfill the job. For example, the AKTA™ systems have to use three different sized mixer chambers (i.e., 0.6ml, 1.4ml and 5ml). The 0.6ml mixer chamber shall be used if the required output flow rates <2ml/min, the 1.4ml one for flow rates between 2 and

12ml/min, while the 5ml one for flow rates between 12 and 25ml/min. Thus the mixer chamber has to be swapped when the desired flow rate changes. Due to this complication, the mixer chamber can not be integrated to the mixer module (stirrer).

There is a need for an integrated mixer chamber design which adjusts the volume in response to an input flow rate. It is also desirable to simplify the mixer module design and improve the homogeneity of solution produced.

Summary of the Invention

The present invention provides an integrated mixer chamber design which is capable of adjusting the volume in response to an input flow rate. Thus, one aspect of the invention provides an integrated system for generating a homogeneous solution from two or more input buffers. The system comprises a mixer chamber including a magnetic stir bar; a means for causing the magnetic stir bar to rotate; and a user interface for input a chosen flow rate. The mixer chamber (mixer house) comprises a mixer chamber body including a movable upper part; one or more solution inlets; a solution outlet; and a means for adjusting the mixer chamber volume. In response to an input flow rate, the mixing chamber volume is adjusted to an optimal volume, by the movement of the movable upper part, controlled by the means for adjusting the mixer chamber volume.

In another aspect of the invention, it is provided a method for generating a homogeneous solution from two or more input buffers. The method includes (a) accepting an user input flow rate; (b) converting the input flow rate to a desired mixer chamber volume; (c) moving the movable upper part of the mixer chamber to arrive at the desired mixer chamber volume; (d) starting, at the input flow rate, a first pumping means to direct the two or more input buffers into the mixer chamber; (e) causing the magnetic stir bar to rotate to mix the input buffers to generate a homogeneous solution; and (f) beginning, at the input flow rate, to release the homogeneous solution through the solution outlet. Brief Description of the Drawings

Figure 1A is a schematic drawing of one example of a mixer chamber (mixer house) according to an embodiment of the invention.

Figure IB is a top view of the magnetic stir bar used in the mixer chamber.

Detailed Description of the Invention

The invention provides a new mixer chamber design that adjusts its volume to an input flow rate by having a movable upper part. It is thus possible to use an optimized volume for any specific flow level within the capacity range of the mixer chamber. It is thus also possible to integrate the mixer chamber to a mixer module.

Thus, in a first aspect of the invention, it is provided a mixer chamber. In one embodiment, it is provided a mixer chamber (mixer house) comprising a mixer chamber body including a movable upper part which defines a mixer chamber volume; one or more inlets for solutions to be mixed in the mixer chamber; an solution outlet; a magnetic stir bar in the mixer chamber volume; and a means for adjusting the mixer chamber volume by controlling the movement of the movable upper part.

In certain embodiments, the one or more inlets of the mixer chamber are integral of the movable upper part. In certain embodiments, there is a single inlet which accepts two or more buffers for mixing. For example, the input and output pump tubing is connected with, for example Valco connection (UNF 10-32 2B) at inlet(s) and outlet.

In certain embodiments, the solution outlet of the mixer chamber is integral of the mixer chamber body and is on the oppose side of the movable upper part. In certain embodiments, the mixer chamber included a means for adjusting the mixer chamber volume by controlling the movement of the movable upper part. Example of a means for adjusting the volume of the mixer chamber is a stepper motor (Figure 1), DC motor with an encoder or a stepper motor with linear actuator. Thus, The correct mixer volume can be adjusted, in response of an input flow rate, by a motor and the user does not need to worry about the optimal mixer volume. It is thus possible to use an optimized volume for the specific flow level, for example between 0.6 and 5ml, or any interval within the capacity of a mixer chamber.

As illustrated in Figure 1 , when a desired volume is chosen, the exemplary stepper motor rotates and the rotating movement is transferred to the lid by outer shape that acts as a cog axel. The lid rotates and has a thread on the inside that creates a movement up or down. This makes the upper part of the mixer chamber to move up or down and therefore increases or decreases the mixer volume. Because of the friction in the o-ring is greater than the friction between the upper part and the lid, the upper part will not rotate, this minimizes wear of the o-ring (Figure 1A) and does not twist the tubings.

In a second aspect of the invention, it is provided a mixer module. In certain embodiments, the mixer module comprises the mixer chamber according to the first aspect of the invention, and means for causing the magnetic stir bar to rotate. For example, the means for causing the magnetic stir bar to rotate is an outer rotating magnet.

In a third aspect of the invention, it is provided an integrated system for

generating a homogeneous solution from two or more input buffers. In one embodiment, it is provided an integrated system for generating a homogeneous solution, which system includes the mixer module according to the second aspect of the invention and a user interface for input a chosen flow rate. In response to the input flow rate, the mixing chamber volume is adjusted to an optimal volume, by the movement of the movable upper part of the mixing chamber, controlled by the means for adjusting the mixer chamber volume.

In one variation of an embodiment, the means for adjusting the mixer chamber volume includes (1) means for converting the chosen flow rate to a desired mixer chamber volume; and (2) means for moving the movable upper part of the mixer chamber body to arrive at the desired mixer chamber volume. Optionally, the means for moving the movable upper part includes a motor connected to the moveable upper part of the mixer chamber body. A specific flow rate corresponds to a specific position of the upper part that gives the mixer volume. All flow rate/ position of the upper part (mixer volume) ratios are listed in a table that are based on experimental data and/or

calculations. The mixer volume can however be chosen by the operator to match a specific method and flow.

In a fourth aspect, the invention provides a method for generating a homogeneous solution from two or more input buffers. According to one embodiment, the method comprises: (a) accepting an user input flow rate;(b) converting the input flow rate to a desired mixer chamber volume; (c) moving the movable upper part of the mixer chamber (according to the first aspect of the invention) to arrive at the desired mixer chamber volume; (d) starting, at the input flow rate, a first pumping means to direct the two or more input buffers into the mixer chamber; (e) causing the magnetic stir bar to rotate to mix the input buffers to generate a homogeneous solution; and (f) beginning, at the input flow rate, to release the homogeneous solution through the solution outlet. In a variation, the flow rate in step (f) is controlled by a second pumping means. Having described some general aspects of the invention, the following passages provide additional details of certain exemplary implementations of the invention.

The purpose of the mixer chamber (mixer house) design is to make sure that two or more input buffers are mixed to give a homogenous buffer composition (solution). Thus, a functioning mixing module consists of two parts, the mixer chamber (mixer house) and means for rotating the magnetic stir bar inside the mixer chamber. The means for rotating the magnetic stir bar contains certain electronics and the driving unit for rotating the magnetic stir bar.

As an example, the rotation of the magnetic stir bar is achieved by an outer rotating magnet. The rotation of this outer magnet, which is a permanent magnet, is controlled by a stepper motor. This is also used to control the rotation speed, which is varied based on the desired flow rate (i.e., volume). The driving unit has a nominal speed of 10 rev/sec and a maximum speed of 15 rev/sec. The outer rotating magnet and stepper motor can be placed outside the mixer chamber (mixer house), in a position adjacent to the magnetic stir bar inside the mixer chamber volume. Alternatively, they could be integrated to the mixer house, on the side of the mixer chamber volume, adjacent to the magnetic stir bar.

Optionally, the mixer module is activated by the pump module which controls the inflow of the two or more buffers.

As described above, the mixing process is performed in a mixing chamber with a magnetic stir bar. To obtain desired homogeneous gradients at different input flow rates, the mixer chamber volume is adjusted in response to the input flow rate. Two

implementations are possible for such an adjustment. In one implementation, the volume adjustment can be performed to arrive at any volume corresponding to the input flow rate (i.e., calculation based on a formula for any input flow rate). Alternatively, several mixer chamber volumes can be preset, each for a flow rate range. For example, a mixer chamber volume of 0.6 ml, 1.4 ml and 5 ml can be chosen, for a flow rate range of 0.5 - <3 ml/min, 3 - <8 ml/min and 8 - 25 ml/min, respectively

All patents, patent publications, and other published references mentioned herein are hereby incorporated by reference in their entireties as if each had been individually and specifically incorporated by reference herein. While preferred illustrative embodiments of the present invention are described, one skilled in the art will appreciate that the present invention can be practiced by other than the described embodiments, which are presented for purposes of illustration only and not by way of limitation. The present invention is limited only by the claims that follow.