Patent Application
20170312709
The present invention relates to an orbital shaker. More in particular, the present invention relates to an orbital shaking device for biotechnological and/or biomedical applications, for example stimulating, sustaining or monitoring microbial and eukaryotic cell growth.
In several fields of technology, fluids and other substances have to be shaken. In biotechnology and biomedical applications, for example, orbital shaking is often used for microbial and cell cultures growing in e.g. Erlenmeyer shake flasks or microtitre plates (also known as microwell plates or microplates), in order to achieve an increased gas-liquid exchange rate, and so an increased oxygen input and CO2 outgassing. In biotechnology applications, shaking amplitudes typically range between 3 and 50 mm, and shaking frequencies between 150 and 1200 rpm (that is, between 2.5 and 20 Hz).
Commercially available orbital shakers for biotechnological applications in laboratory settings generally have either (i) a three-point shaking system consisting of three bearings with eccentric axes in a triangle under the shaker platform, one of the axes being driven by a motor, or (ii) a central drive, in combination with a parallelogram. In both cases, internal counterweights are positioned directly under the shaker platform, which results in (full or partial) equilibration in the horizontal plane, and an incomplete (but mostly acceptable) equilibration in the vertical plane.
European Patent EP 2 301 679 discloses an orbital shaker provided with counterweights both above and below the orbitally shaking platform. An embodiment comprises four counterweights rotating around two vertical axes. The trajectories of the two lower counterweights cover most of the underside of the platform. In another embodiment the trajectory of a single lower counterweight extends over substantially all of the underside of the platform.
A disadvantage of the shaker of EP 2 301 679, and of the commercially available orbital shakers mentioned above, that they have both moving and stationary parts underneath the platform. It is often desired to monitor microbial and eukaryotic cell cultures which are being shaken, for example to monitor their growth. It is also desired to supply cultures, for example algae, with a suitable amount of light. To this end, it is desired to put imaging devices, such as scanners and/or cameras, and/or illumination devices, such as lamps, underneath the platform which is, for this purpose, made transparent or provided with suitable openings. However, mounting imaging devices and/or illumination devices underneath the platform is typically not possible with prior art devices due to the presence of the drive system and/or the counterweights.
Another disadvantage of the shaker of EP 2 301 679 is that only one axis is driven by the motor, the other axes being indirectly driven by the platform. Practice has shown that such arrangements are subject to significant stress, and hence to significant wear, when used at the shaking frequencies which are common in biotechnical applications (typically about 150 to 1200 rpm). It is especially at the higher rotational speeds that this wear hampers the long-term reliability of the shaking device. Also the commercially available shaker devices mentioned above, having a three-point system or a central drive with a parallelogram, are known to be prone to failure, especially at higher speeds (above 800 rpm).
U.S. Pat. No. 5,372,425 discloses a shaker apparatus provided with drive means located centrally underneath the platform. The shaker apparatus of U.S. Pat. No. 5,372,425 is therefore unsuitable for mounting imaging devices and/or illumination devices underneath the platform.
It is an object of the present invention to solve these and other problems of the state of the art by providing an orbital shaker device which allows room for an imaging and/or illumination apparatus (or apparatuses) underneath the moving platform while being able to operate at shaking frequencies in the biotechnological range, that is, between approximately 150 and 1200 rpm.
It is a further object of the present invention to provide an orbital shaker which allows the counterweights to be adapted to the load in order to reduce or substantially eliminate vibrations at varying numbers of containers.
Accordingly, the present invention provides an orbital shaker device for biotechnological and/or biomedical applications, comprising:
By providing two eccentric couplings near two edges of the platform, the couplings are spaced apart from the containers receiving part of the platform, and hence from the bottom side of the containers receiving part. As a result, the axes and/or motors driving the couplings can also be spaced apart from the containers receiving part of the platform. In addition, providing two instead of three or more eccentric couplings results in a simpler construction and a reduced wear.
By positioning the counterweight units approximately in the plane of the platform, or more specifically, in the plane of the combined center of gravity of the platform and the containers when in use, that is, approximately in the plane of the center of gravity of the loaded platform when in use, not only the horizontal balancing is optimized, but also the vertical balancing, as the counterweights are at the same height as the combination of the platform and its load. In addition, mounting the counterweights both in approximately the plane of the center of gravity of the platform when loaded with containers and near edges of the platform ensures that the counterweights are not located underneath the platform, thus keeping the bottom side of the platform free for imaging and/or illumination apparatus(es) and other purposes.
By driving both eccentric couplings instead of only one, a better synchronization of the couplings, a reduced amount of vibrations and a significantly reduced wear are achieved.
It is noted that German Patent DE 33 19 574 discloses a shaking device in which a counterweight is located just beneath the platform in order to bring the counterweight as close as possible to the center of gravity of the loaded platform. However, by mounting the counterweight just beneath the platform, a vertical imbalance will unavoidably remain. In addition, the position of the counterweight will hinder taking images of the platform from underneath.
It is further noted that International Patent Application WO 2010/037862 discloses an orbital shaking device provided with a flatbed scanner for generating two-dimensional images of the bottom sides of microtitre plates. WO 2010/037862 discloses no details of the shaking mechanism.
In the device of the present invention, the containers are preferably biotechnological containers, such as microplates, laboratory beakers and/or Erlenmeyer flasks. In the case of microplates, the containers will be relatively shallow and have a limited height. When the platform is receiving a single layer of relatively shallow containers, the combined center of gravity will be only slightly above the platform and may even substantially coincide with the plane of the platform.
The at least one motor may drive the eccentric couplings in several ways. In an embodiment, each eccentric coupling is driven by a respective vertical axis, the axes being driven by a single motor. That is, both axes are driven by a single motor, using a mechanism for transferring the rotation of the motor to the eccentric couplings via the vertical axes on which the eccentric couplings are mounted. In one such embodiment, the single motor is connected to the axes through right-angle gear boxes. This allows the motor to be arranged horizontally, having for example horizontal drive axes extending at both ends of the motor, which drive axes are coupled to the vertical axes by means of the right-angle gear boxes. Such an arrangement allows the motor to be arranged at almost any convenient distance from the platform, thus providing ample space for an imaging and/or illumination apparatus (or apparatuses). Alternatively, the single motor may be connected to the vertical axes through a belt, in combination with suitable wheels for driving the belt and the vertical axes. When using a belt, it is preferred to use a toothed belt to avoid slip and thereby guarantee the synchronous rotation of the eccentric couplings.
Instead of using a single motor for driving all eccentric couplings, each eccentric coupling may be driven by a separate motor. Such an embodiment removes the need for additional axes or a belt, but requires an additional motor. Particularly in such an embodiment, the device preferably comprising sensors for sensing the speed of the motors. Such sensors allow the rotational speed of the motors to be kept equal, thereby ensuring a synchronous rotation of the eccentric couplings. To this end, the device of the present invention may further comprise a control unit for controlling the speed of the motors, preferably in response to the sensed speed. A speed control unit may also be advantageous in embodiments having a single motor.
In order to monitor the growth (or death) of microorganism cultures or eukaryotic cell cultures, the device of the present invention may comprise an imaging unit located underneath the platform, said platform preferably being provided with openings and/or transparent parts allowing imaging the containers. The imaging unit may comprise a single camera or an array of cameras. Alternatively, or additionally, the imaging unit may comprise a scanner or other imaging means. The imaging unit may further comprise a processor for image processing and analysis. The processor uses techniques which may be known per se.
In a particularly advantageous embodiment, the control unit is arranged for reducing the speed of the at least one motor in preparation for imaging. That is, the shaking frequency is reduced when an image, or a series of images, is to be made. This allows better quality images to be made. The motor, and hence the platform, may come to a standstill when an image is made, but this is only required when using a scanner and is not required when using a camera having a relatively short exposure time. It will be understood that the motor speed is brought back to its original value when the imaging is completed.
When a single layer of relatively low containers is used, counterweight units having a fixed mass are typically suitable. However, when higher containers are used, or containers having relatively large variation in the weight of their contents, or when containers are stacked, then counterweight units exerting a fixed centrifugal force at a certain speed are often less suitable. In a particularly advantageous embodiment, therefore, the counterweight units are adjustable. That is, the mass of the counterweights can be increased or decreased, or be moved relative to the eccentric couplings so as to have a greater or lesser counterbalancing effect. In an embodiment, therefore the counterweight units are arranged for adding and/or removing counterweights. In another embodiment, the counterweight units may comprise counterweights having an asymmetrical mass distribution relative to an axis and which can be rotated about said axis, so as to increase or decrease their counterbalancing effect. The centrifugal force at a certain rotational speed may alternatively, or additionally, be increased or decreased by changing the distance between a counterweight's center of gravity and the axis around which it rotates.
The platform may be arranged for stacking containers and may for example be provided with support members to facilitate stacking and to prevent stacks of containers from falling over.
Although the device may have a plurality of eccentric couplings for rotatably coupling the platform to the frame, for example four, in a preferred embodiment the device has only two eccentric couplings. This limited number of joints ensures a proper functioning of the device with a minimum number of parts.
The present invention also provides a use of an orbital shaker device as defined above when provided with adjustable counterweight units, the use comprising the step of adjusting the counterweight units. The use may further comprise the step of adding or removing counterweights, in particular when placing a load on the platform, or when increasing or decreasing the load of the platform.
The present invention will further be explained with reference to exemplary embodiments illustrated in the drawings, in which:
The merely exemplary embodiment of the device 1 shown in
The platform 15 is arranged for receiving and accommodating containers 50, as will later be explained in more detail with reference to
A motor 19 drives the eccentric couplings 13 & 14 via horizontal axes 23 & 24, orthogonal gearboxes 21 & 22, and vertical axes 11 & 12. The eccentric couplings 13 & 14 transform the rotation of the axes 11 & 12 into an orbital movement of the platform 15. The orthogonal gearboxes 21 & 22, which may be known per se, transform the horizontal rotation of the axes 23 & 24 into a vertical rotation of the axes 11 & 12.
The arrangement of the motor 19 and the horizontal and vertical axes as shown in
In order to balance the orbital movement of the platform 15 and to counter vibrations of the device 1, counterweight units 17 & 18 are provided. In the embodiment of
It is noted that the amplitude of the platform 15 is defined by the spacing between the rotational axis of the eccentric coupling and the rotational axis of the shafts (26 in
By mounting the counterweight units on the eccentric couplings, either directly or indirectly via a shaft, two important advantages are achieved. A first advantage is that these counterweights can be positioned approximately at the level of the center of gravity of the loaded platform, as will be explained later in more detail. A second advantage is that the counterweights are spaced apart from the containers receiving part of the platform 15. More in particular, the counterweights are located to the sides of the platform 15 and do not obstruct the space above or below the platform 15, as in some prior art devices. In
It can thus be seen that the present invention provides space underneath the movable platform by two related measures:
It is noted that in the embodiment of
In embodiments having multiple motors the movement of the eccentric couplings is not mechanically synchronized, as in the embodiment of
The side view of
The perspective view of
A top view of the device 1 is shown in
An alternative embodiment of the device according to the present invention is schematically illustrated in
Another adaptation of this embodiment is the altered counterweight unit 18 (as well as 17, which is not shown, and any other counterweight unit the device may have). The more containers 50 are stacked on the platform 15, the higher the center of gravity of the moving components (containers plus platform) will be. An optimal compensation of the imbalance caused by the eccentric movement of the platform is however achieved when the counterweights are located at about the same height as the center of gravity of the moving components (containers plus platform). To be able to provide an optimal compensation with various loads, this embodiment has adjustable counterweight units. That is, the mass and the height of the counterweight unit can be adjusted to match the load.
In the embodiment of
In a preferred embodiment, the dimensions and the mass of each counterweight is chosen so as to match the dimensions and the mass of the average container, or of the average platform provided with containers. The counterweights are provided with suitable means for holding them in place when stacked.
In the embodiments shown, the shaker device has only a single platform, on which containers may or may not be stacked. Embodiments can be envisaged in which multiple platforms are used, arranged one above the other, and separated by pairs of shafts and eccentric couplings. That is, each platform may be carried by a pair of eccentric couplings from which shafts protrude which support the next level of eccentric couplings. By suitably arranging the eccentric couplings relative to each other, the successive platforms may make opposite rotational movements so as to counterbalance each other. In such embodiments, separate counterweight units would not be required.
A top view of an eccentric coupling 14 with an adjustable counterweight unit 18 as may be used in the embodiment of
The counterweight unit 18 of
In an embodiment of the kind illustrated in
In a particular advantageous embodiment, acceleration sensors are mounted on the frame 10 of the device for sensing any vibrations. A monitoring unit may be arranged for using the acceleration data produced by the sensors to indicate whether the counterweight units need adjusting.
In the embodiment of
The device of the present invention is capable of operating at shaking frequencies (that is, rotational velocities) in the biotechnological and biomedical range, that is, between approximately 150 and 1200 rpm (revolutions per minute), without undue vibrations. A preferred range is 200 to 700 rpm, more in particular 250 to 500 rpm, although other frequency ranges may also be used, depending on the particular application. It is noted that at an orbital movement amplitude of 50 mm a rotational speed of 200 to 300 rpm is generally preferred, while at an amplitude of 3 mm a speed of 800 to 1200 rpm is generally preferred.
The containers 50 are preferably microwell containers or micro titer plates configured for biotechnological and/or biomedical purposes, such as growing and/or sustaining bacteria and/or eukaryotic cell cultures. However, the device of the present invention may also be utilized in other fields of technology and the containers may be designed for containing paint, for example.
It will be understood that the description of the invention given above is not intended to limit the invention in any way. Singular nouns and the articles “a” and “an” are of course not meant to exclude the possibility of plurals. Devices or components mentioned in this document may be replaced with their successors, even if these successors are not yet known at the time of writing. As is well established in the law of patents, the abstract should never be used to limit the scope of the claims, and neither should reference numbers in the claims.
It will further be understood by those skilled in the art that the present invention is not limited to the embodiments mentioned above and that many additions and modifications are possible without departing from the scope of the invention as defined in the appending claims.
| Number | Date | Country | Kind |
|---|---|---|---|
| 14193009.9 | Nov 2014 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2015/076386 | 11/12/2015 | WO | 00 |
