GB2450718A

GB2450718A - Cell stretching device

Info

Publication number: GB2450718A
Application number: GB0712925A
Authority: GB
Inventors: Jonathan Michael Rigelsford
Original assignee: BIO MANIPULATION Ltd
Current assignee: BIO MANIPULATION Ltd
Priority date: 2007-07-04
Filing date: 2007-07-04
Publication date: 2009-01-07
Also published as: GB0712925D0

Abstract

A cell stretching device, comprising first fixing means 130 for fixing to a first end of a biological sample; second fixing means 140 for fixing to a second end of the biological sample; a screw-threaded rod 116 arranged to cooperate with the first and/or second fixing means and be rotatable about its elongate axis to move the first fixing means relative to the second fixing means; and rotate means 122 for rotating the screw-threaded rod.

Description

BIOLOGICAL SAMPLE MANIPULATION DEVICE

Field of the Invention

Embodiments of this invention relate to a biological sample manipulation device.

Background to the Invention

Organic cells can be grown or placed onto a cell substrate. The substrate is then stretched using a stretching device, which stretches the cells on the substrate. The cells can then be studied to determine the effects of the stretching.

The substrate must be stretched by very small amounts to study the effects of stretching the cells. The accuracy of the amount by which the cell substrate is stretched must be high, and therefore mechanical play and tolerances of the mechanical components of the stretching device must be low. Furthermore, the amount by which the substrate is stretched must be accurately known so that reliable * experimental results are obtained. As a result, devices for stretching the substrate are * costly.

It is an object of embodiments of the invention to at least mitigate one or more of the

problems of the prior art. S. *

Summary of the Invention S.... * 25

According to a first aspect of embodiments of the invention, there is provided a biological sample manipulation device, comprising first fixing means for fixing to a first end of a biological sample; second fixing means for fixing to a second end of the biological sample; a screw-threaded rod arranged to cooperate with the first and/or second fixing means and be rotatable about its elongate axis to move the first fixing means relative to the second fixing means; and rotate means for rotating the screw-threaded rod.

Thus, a biological sample manipulation device may be provided having a simple construction and that may be constructed using low cost components. The device has little mechanical play and can therefore accurately stretch or compress the biological sample by small amounts.

Embodiments of the invention can also be made small enough so that one or more devices can easily fit within an incubator. Thus, the biological sample or samples do not need to be removed from the incubator before they are manipulated.

In certain embodiments, the rotate means comprises a stepper motor. Using a stepper motor allows a shaft of the motor to rotate by a fixed amount or multiples of a fixed amount. For example, the stepper motor can rotate the screw-threaded rod in 2048 steps per revolution of the screw-threaded rod, if the shaft is connected to the screw-threaded rod. Such motors are readily available for low cost. Using a stepper motor allows the amount by which the stepper motor has rotated its shaft, and thus the amount by which the biological sample has been stretched or compressed, to be accurately known.

In certain embodiments, the screw threaded rod is arranged to be rotatable in a first direction to separate the first and second fixing means, and rotatable in a second direction to bring the first and second fixing means together. Therefore, the biological sample can be stretched and compressed, and the stretching or compression can be released. Preferably, the screw-threaded rod is arranged such that one revolution of * the rod moves the first and second fixing means further apart or closer together by 0.5 * 25 mm. Therefore, the biological sample can be stretched or compressed by a small amount. For example, where a stepper motor is used with 2048 steps per revolution, for each step of the motor, the first and second fixing means can be separated or brought together by 0.5 mm / 2048 = 0.244 JIm, thus stretching (or compressing) the biological sample by the same amount. Such screw-threaded rods are available for low cost and can be made of, for example, plastic or stainless steel.

In certain embodiments, the device comprises a fixed rod on which the first fixing means is slidably mounted and on which the second fixing means is fixed. Therefore, the first and second fixing means can be linearly separated or brought together.

Preferably, the screw-threaded rod rotates to slide the first fixing means along the fixed rod. Preferably, the first fixing means includes a screw-threaded through hole for cooperating with the screw-threaded rod such that rotation of the screw-threaded rod causes the first fixing means to slide along the fixed rod. A good fit between the screw-threaded rod and the through-hole can be achieved with low cost manufacturing such that there is little mechanical play between the screw-threaded rod and the first fixing means. The biological sample can therefore be stretched or compressed by an accurate amount.

In certain embodiments, the device comprises a substantially sealed case. The case can be filled with fluid that enables growth or preservation of the biological sample that is fixed between the first and second fixing means. Preferably, the case comprises an elongate housing with an open end and a cap that cooperates releasably with the open end of the housing to substantially seal the open end of the housing.

Such a case can be manufactured to a low cost. Furthermore, the cap can be loosened from the housing to allow gases such as carbon dioxide to enter and/or exit the case.

* According to a second aspect of embodiments of the invention, there is provided a * controller for controlling a biological sample manipulation device according to the first aspect of embodiments of the mvention. Preferably, the controller controls a ***** plurality of biological sample manipulation devices as claimed in claim 1. Therefore, *. multiple biological sample manipulation experiments can be conducted in parallel.

For example, multiple different experiments, repeat experiments and/or control * * experiments may be conducted in parallel. This may decrease experimentation time * 25 and/or increase the reliability and/or accuracy of results.

In certain embodiments, the controller controls the stepper motor such that the biological sample is stretched and/or compressed according to a profile. Therefore, the controller can manipulate the biological sample without substantial interaction by a user. For example, the profile is specified by specifying an amount of stretch and/or compression and a rate of change. These parameters may be specified and then the controller may be left to stretch and/or compress the biological sample accordingly.

Brief Description of the Drawings

Embodiments of the invention will now be described by way of example only, with reference to the accompanying drawings, in which: Figure 1 shows a perspective view of a biological sample substrate manipulation device according to embodiments of the invention; Figure 2 shows a cross-sectional side view of a device according to embodiments of the invention; Figure 3 shows an example of a biological sample comprising a substrate with cells mounted on the substrate; Figure 4 shows a cross-sectional side view of the device of figure 2 with a cell substrate fixed into it; Figure 5 shows an alternative fixing means; * Figure 6 shows another alternative fixing means; S...

Figure 7 shows a perspective view of an alternative clamp; * Figure 8 shows a perspective view of another alternative clamp; and * 25 Figure 9 shows an alternative embodiment of the invention.

Detailed Description of Embodiments of the Invention The biological sample manipulation device 100 of figure 1 for manipulating (stretching and/or compressing) a biological sample comprises a cap 102 that comprises a hollow cylindrical portion 104 and a solid cylindrical portion 106 of larger diameter than the first cylindrical portion 104. The first and second portions 104 and 106 share a common axis. An inner surface 108 of the first portion 104 is screw-threaded to cooperate with a screw-threaded end of a housing (not shown) to form a case as indicated in more detail later in this document.

The biological sample may comprise, for example, a group of cells such as a ball of cells, or a substrate on which one or more groups of cells are mounted (for example, the cells may be grown on the substrate or placed on the substrate). Alternatively, the biological sample may comprise, for example, bone, ligaments or tendons. These may be mounted within a biological sample manipulation device according to embodiments of the invention directly or mounted on a substrate first.

The device 100 includes a fixed rod 110, with a length of approximately 100 mm, that is fixed at one end 112 to an end 114 of the second portion 106 of the cap 102 such that the fixed rod 110 passes through the first portion 104 of the cap 102. The fixed rod 110 is fixed such that it is parallel to the axis of the first and second portions 104 and 106 of the cap 102. The fixed rod 110 has a rectangular cross-section.

The device 100 also includes a screw-threaded rod 116 with a length of approximately * 120 mm. The screw-threaded rod 116 is arranged to be parallel to the fixed rod 110 and pass through a through hole 118 in the second portion 106 of the cap 102. The screw-threaded rod 116 is coupled at one end (not shown) to a shaft 120 of rotate means that comprises a stepper motor 122. The stepper motor 122 is attached to an end 124 of the second portion 106 of the cap 102 that is opposite to the end 114. The stepper motor 122 is attached via two supports 126 and 128 such that it is held in a * 4 fixed position relative to the cap 102. The screw-threaded rod 116 can rotate freely in I..I * 25 the th.rough hole 118 in the cap 102.

The device 100 further comprises first fixing means 130. The first fixing means 130 comprises a substantially semicircular element, and includes a first rectangular through hole 132 through which the fixed rod 110 passes such that the first fixing means 130 is slidably mounted on the fixed rod 110. The first fixing means 130 also includes a second through hole 134. The second through hole 134 is screw-threaded and cooperates with the screw-threaded rod 116 such that when the screw-threaded rod 116 rotates about its elongate axis, the first fixing means 130, which is prevented from rotating with the screw-threaded rod 116 by the fixed rod 110, slides linearly along the fixed rod 110. Rotation of the screw-threaded rod 116 in a first direction thus moves the first fixing means 130 along the fixed rod 110 towards the cap 102, whereas rotation of the screw-threaded rod 116 in a second direction moves the first fixing means 130 along the fixed rod 110 away from the cap 102.

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The first fixing means 130 includes a clamp 135 that comprises a first clamp portion 136 that is fixed to the first fixing means 130 and a second clamp portion 137 that can move relative to the first clamp portion 136. A screw 138 passes through and can rotate freely within a through hole through the second clamp portion 137. The screw 138 also passes though a through hole in the first clamp portion 136 and cooperates with screw threaded side walls of the through hole. The screw 138 can be used to bring the first 136 and second 137 clamp portions together such that an object, such as an end of a biological sample, can be clamped therebetween.

The first fixing means 130 can be easily manufactured (for example, from plastic and/or stainless steel) such that there is little mechanical play between the screw thread of the through hole 134 and the screw-threaded rod 116. Furthermore, even if * there is mechanical play within the stepper motor 112 such that a single step of 1/2048 of a revolution of the shaft 120 has some error, then because a full revolution of the screw threaded rod 116 moves the first fixing means 130 only by 0. 5 mm the error in the movement of the first fixing means 130 is very small. The stepper motor 122 may * * include more steps than necessary to reduce the error in the movement of the first fixing means 130. For example, where it is desired to stretch or compress the * biological sample only in steps of approximately 1.im, then only 500 steps of the S....

* 25 stepper motor 122 are required, as 0.5 / 500 = 1 tm. However, for example, if the error in rotation of the shaft 120 due to mechanical play depends on the step size, then the error in rotation of the shaft 120, and hence error in the movement of the first fixing means 130, may be reduced by using a stepper motor with more steps per revolution, and advancing the stepper motor by multiple steps when it is desired to stretch or compress the biological sample.

For example, where the stepper motor 122 makes one revolution in 2048 steps, and the first fixing means moves by 0.5 mm per revolution of the screw threaded rod 116, and it is desired to apply a stretch of 0.001 inches (0.0254 mm) to a biological sample fixed between the first and second fixing means 130 and 140, then the stepper motor must make approximately 104 steps to achieve this amount of stretch. The mechanical play from the stepper motor therefore adds very little error to the stretch amount. Furthermore, if the stepper motor makes, for example, one or two (or more) S too many or few steps, then this will add only a small amount of error to the amount of stretch.

The device 100 also includes a second fixing means 140. The second fixing means comprises a substantially semicircular element, and includes a first rectangular through hole 142 through which the fixed rod 110 passes. However, the second fixing means 140 is fixed to the fixed rod 110 such that it cannot slide along the fixed rod 110. This may be achieved, for example, by glue within the through hole and/or a screw (not shown) that fixes the second fixing means 140 to the fixed rod 110. The second fixing means 140 also includes a second through hole 144. The screw-threaded rod 116 passes through the second through hole 144 and can rotate freely within the second through hole 144. Therefore, the screw-threaded rod 116 is held in position (i.e. substantially parallel to the fixed rod 110) by the second fixing means :. 140 which is attached to the fixed rod 110, and the second fixing means can rotate about its elongate axis. A nut 150 is attached to the end 152 of the screw threaded rod S...

116 and prevents the end 152 of the screw threaded rod 116 from passing through the through hole 144 in the second fixing means 140. I..

The second fixing means 140 includes a clamp 145 that comprises a first clamp portion 146 that is fixed to the second fixing means 140 and a second clamp portion * 25 147 that can move relative to the first clamp portion 146. A screw 148 passes through and can rotate freely within a through hole through the second clamp portion 147.

The screw 148 also passes though a through hole in the first clamp portion 146 and cooperates with screw threaded side walls of the through hole. The screw 148 can be used to bring the first 146 and second 147 clamp portions together such that an object, such as an end of a biological sample, can be clamped therebetween.

Figure 2 shows a cross-section 200 of a side view of the device 100 of figure 1. In this figure, the coupling between the screw-threaded rod 116 and the shaft 120 of the stepper motor 122 can be seen. The coupling comprises a hollow cylindrical coupling rod 202. An end 204 of the screw-threaded rod 116 projects into the coupling rod 202 and the screw-threaded rod 116 is held in place in the coupling rod 202 by a first grub screw 206. Similarly, an end 208 of the shaft 120 of the stepper motor 122 projects into the coupling rod 202 and the shaft 120 is held in place in the coupling rod 202 by a second grub screw 208. Rotation of the shaft 120 of the stepper motor 122 is translated to rotation of the screw-threaded rod 116 via the coupling rod 202, which also rotates with the shaft 120 and screw-threaded rod 116.

The device 200 shown in figure 2 also includes a substantially cylindrical housing 212 that has a closed conical-shaped first end 214 and an open end 216 with screw-threaded side walls. The screw-threaded side walls cooperate with the screw-threaded inner surface 108 of the first portion 104 of the cap 102 such that the cap 102 can be screwed onto the housing 212 to form a case around the first and second fixing means and 140 and any biological sample fixed therebetween. The cap 102 can be loosened from the housing 212 by unscrewing to allow gases such as carbon dioxide to enter and/or exit the case whilst holding the housing 212 in a fixed position relative to the cap 102. In embodiments of the invention, the case may contain fluid, such as growth fluid, for example Dulbecco's Modified Eagles Medium (DMEM) :1.::: supplemented with foetal calf serum, antibiotics and glutamine.

The above described embodiment of a biological sample manipulation device can be made to low cost as the components are readily available and/or can be easily *: * manufactured, for example from plastic and/or metal (such as stainless steel) components. The device can also be made such that extremely fine and accurate * **.** * 25 manipulation of a biological sample can be performed with little mechanical play between the components of the device.

For example, the screw-threaded rod 116 can be a plastic rod such that if the rod 116 makes one revolution or turn about its elongate axis, the first fixing means 130 moves towards or away from (depending on the direction of rotation) the second fixing means 140 by 0.5 mm. Alternatively, the screw-threaded rod 116 may be made of other materials, such as stainless steel, and/or may move the first fixing means more or less than 0.5 mm per revolution.

The stepper motor 122 may have 2048 steps per revolution of the shaft 120. Such stepper motors are readily available at relatively low cost. If the screw-threaded rod 116 moves the first fixing means 130 by 0.5 mm per revolution of the screw-threaded rod 116, then each step of the stepper motor can move the first fixing means by 0.5 / 2048 = 0.244.tm. The stepper motor 122 can be controlled by a controller (not shown) to rotate the shaft 120 of the motor 122 in steps such that the first fixing means 130 is moved in multiples of 0.244 urn towards or away from the second fixing means, thus applying compression or stretching to a biological sample fixed between the first and second fixing means 130 and 140. Other stepper motors with differing numbers of steps and/or other screw-threaded rods may be used such that each step of the stepper motor moves the first fixing means 130 by some other amount.

Figure 3 shows a biological sample that comprises a cell substrate 300 with a group of cells 302 mounted on the substrate 300. The substrate 300 is of an elongate rectangular shape such that it has a first end 304 and a second end 306 opposite the first end 304. The group of cells 302 may grow anywhere on the cell substrate 300 and may form multiple separate clusters. Alternatively, a mask may be used such that * the cells 302 grow into a certain shape. The substrate 300 may comprise a flexible membrane chemically modified to allow the attachment and growth of mammalian cells such as, for example, Flexiperm (Greiner) or Polydimethylsiloxane surface modified in plasma reactor. ** a

Figure 4 shows the cell manipulation device 200 of figure 2 with the cell substrate 300 fixed between the first and second fixing means 130 and 140. More specifically, the a.....

first 136 and second 137 clamp portions of the clamp 135 of the first fixing means have been brought together using the screw 138 such that the first end 304 of the substrate 300 is clamped between the first 136 and 137 clamp portions. Similarly, the first 146 and second 147 clamp portions of the clamp 145 of the second fixing means have been brought together using the screw 148 such that the second end 306 of the substrate 300 is clamped between the first 146 and 147 clamp portions. Therefore, for example, if the first 130 and second 140 fixing means are moved apart from each other by rotating the screw threaded rod 116, the cell substrate 300, and the cells 302 mounted thereon, will be stretched.

Figure 5 shows a front view of an alternative fixing means 500 that may be used in place of the first and/or second fixing means. The fixing means 500 comprises a substantially semicircular element that includes a first rectangular through hole 502 through which the fixed rod 110 may pass, and second through hole 504 through which the screw threaded rod 116 may pass. Side walls of the second through hole 504 may be screw threaded to cooperate with the screw threaded rod 116.

The alternative fixing means 500 includes a clamp 510 comprising a first clamp portion 512 that is fixed to the alternative fixing means 500, and a second clamp portion 514 that may move relative to the first clamp portion 512. A screw 516 passes through a through hole 518 in the first clamp portion 512 and a through hole 520 in the second clamp portion 514. The screw 516 rotates freely within the through hole 518 and cooperates with screw threaded side walls of the through hole 520.

The first 512 and second 514 clamp portions have respective facing projections 522 and 524. The screw 516 is used to bring the first 512 and second 514 clamp portions together such that an object, for example and end of a biological sample, may be clamped between the projections 522 and 524. The screw 516 is located such that the second clamp portion 514 tilts slightly relative to the first clamp portion 512 when the first 512 and second 514 clamp portions are brought together. Therefore, corners of the projections 522 and 524 are brought together with more force than the majority of the projections 522 and 524, and this may lead to an improved grip of the object when compared to the clamps 135 and 145 shown in figure 1.

* 25 Figure 6 shows a front view of an alternative fixing means 600 that may be used in place of the first and/or second fixing means. The fixing means 600 comprises a substantially semicircular element that includes a first rectangular through hole 602 through which the fixed rod 110 may pass, and second through hole 604 through which the screw threaded rod 116 may pass. Side walls of the second through hole 604 may be screw threaded to cooperate with the screw threaded rod 116.

The alternative fixing means 600 includes a clamp 610 comprising a first clamp portion 612 that is fixed to the alternative fixing means 600, and a second clamp portion 614 that may move relative to the first clamp portion 612. A screw 616 passes through a through hole 618 in the first clamp portion 612 and a through hole 620 in the second clamp portion 614. The screw 616 rotates freely within the through hole 618 and cooperates with screw threaded side walls of the through hole 620.

The first clamp portion 612 includes a projection 622, and the second clamp portion 614 includes a recess 624 such that when the first 612 and second 614 clamp portions are brought together, the projection 622 is located within the recess 624. This may provide an improved grip of an object by the clamp 610 when the first 612 and second 614 clamp portions are brought together. Furthermore, the object, which may be a biological sample, may include a through hole through which the projection 622 may project, thus providing a secure fixing for the object when the first 612 and second 614 projections are brought together.

Figure 7 shows the clamp 610 in more detail. The substantially semicircular element and the screw are not shown for clarity. It is shown that the projection 622 extends across the entire width of the first clamp portion 612, and the recess 624 extends across the entire width of the second clamp portion 624. Therefore, when an object is clamped using the clamp 610, the object is gripped across the entire width of the clamp portions 612 and 614, between the projection 622 and the recess 624. a..

Therefore, when the object is stretched or compressed using the cell manipulation device, the object is subjected to a force that is substantially uniform across the width of the object.

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Figure 8 shows an alternative clamp 800, which may be easier and/or cheaper to *SSSS* * 25 manufacture than that shown in figure 7, and may be included with the first and/or second fixing means of the biological sample manipulation device. The clamp 800 includes a first clamp portion 802 that is fixed to, for example, the alternative fixing means 600 shown in figure 6, and a second clamp portion 804 that may move relative to the first clamp portion 802. The first clamp portion 802 includes a through hole 806 through which a screw (not shown), such as the screw 616 shown in figure 6, may pass and rotate freely. The second clamp portion 804 includes a screw threaded through hole 808 through which the screw may pass, and the screw threaded side walls of the through hole 808 may cooperate with the screw.

The first clamp portion includes a nipple 810 that corresponds to a depression 812 in the second clamp portion 804 such that when the first 802 and second 804 clamp portions are brought together, the nipple 810 is located within the depression 812.

Thus, an object may be clamped between the nipple 810 and depression 812. In certain embodiments, the depression 812 may instead be a through hole to facilitate cleaning of the second clamp portion 804.

The object clamped between the nipple 810 and the depression 812 may include a through hole though which the nipple projects when the object is clamped by the clamp 800, thus providing a secure grip without deforming the object.

A screw 616 passes through a through hole 618 in the first clamp portion 612 and a through hole 620 in the second clamp portion 614. The screw 616 rotates freely within the through hole 618 and cooperates with screw threaded side walls of the through hole 620.

In alternative embodiments of the invention, the fixed rod 110 may be replaced by, for example, two or more substantially parallel rods or one or more rods of different :..::: cross-sectional shape. S..

In alternative embodiments of the invention, or alternative uses of the embodiments of the invention described herein, the biological sample to be stretched or compressed does not need to be mounted on a substrate to be used within the biological sample mampulation device. Instead, for example, a group of cells may be fixed between the

SSI

* 25 first and second fixing means. The first and second fixing means may be modified to suit the arrangement of the group of cells and the intended use of the cell manipulation device. For example, the group of cells may be a ball of cells. The first and second fixing means may be modified so instead of the clamps 135 and 145, the first and second fixing means comprise respective plates between which the ball of cells can be compressed. The compression of the ball of cells may also hold the ball of cells in place between the first and second fixing means.

In embodiments of the invention, most or all of the components of the biological sample manipulation device (except for certain components of the stepper motor) may be manufactured from plastic, such as PTFE and/or polypropylene and/or metal such as, for example, stainless steel and/or aluminium. The components may be manufactured to low cost and/or readily available, and may be assembled to low cost.

The cells on the cell substrate or the group of cells may be grown within the cell manipulation device, or inserted once the cells have grown.

A plurality of biological sample manipulation devices may be provided such that a plurality of experiments on biological samples may be conducted in parallel. For example, different experiments, repeat experiments and/or control experiments may be conducted simultaneously. One or more controllers (not shown) may be provided to control the stepper motors such that the desired amount of stretching or compression is applied to the biological samples mounted within the biological sample manipulation devices. For example, where repeat or control experiments are taking place, the same amount of stretching or compression may be applied.

In embodiments of the invention, a controller controlling a biological sample :. manipulation device may be provided with a user interface such that the stretching or compression of the biological sample within thedevice may be controlled via the user interface. For example, a user may specify via the user interface that the first and second fixing means should be separated by a certain amount at a certain rate of change, thus specifying a profile for stretching the biological sample. Where multiple experiments are conducted in parallel, the user may specify multiple profiles for different devices, or may specify the same profile for different devices, for example * 25 where the devices are used to conduct repeat and/or control experiments.

Devices according to embodiments of the invention described herein are of a compact size and do not substantially change their size when a large stretch or compression is applied to the biological sample mounted therein.

The elongate housing of the case of the cell manipulation device may be substantially transparent such that the cells therein may be examined, for example using a microscope, without removing the elongate housing from the device. If there is any fluid present within the case of the device, the fluid may also be substantially transparent for the same purpose. Alternatively, the elongate housing and any fluid may be removed before the cells are examined.

Devices according to embodiments of the invention may be positioned vertically such that sediments settle away from the cells and/or any loosened cap or through holes through the cap of the device. For example, the device 200 of figure 2 may be positioned such that the conical end 214 of the elongate housing 212 is mounted at the bottom, whereas the cap 102 is mounted towards the top and is located substantially above the conical end 214. Therefore, any sediments within the case of the device 200, such as any sediments present in the fluid within the case and/or produced by the cells within the device, may tend to collect in the conical end 214 of the elongate housing 212.

Figure 9 shows a biological sample manipulation device 900 according to alternative embodiments of the invention. The device 900 includes end pieces 902 and 904 that are fixed to each other via a fixed rod 905. A screw threaded rod 906 passes through and can rotate freely within a through hole 908 in the end piece 904. The screw threaded rod also passes into a depression or through hole 910 in the end piece 902 and can rotate freely therein. The end piece 902 includes a clamp and/or fixing means 902 for fixing to an object to be manipulated (such as, for example, an end of a biological sample). S..

The device 900 also includes a second fixing means 914 that includes a clamp 916.

The second fixing means 914 includes a through hole 918 through which the fixed rod *5***S * 25 905 passes such that the second fixing means 914 is slidably mounted on the fixed rod 905. The second fixing means includes another through hole 920 through which the screw threaded rod 906 passes. The through hole 920 includes screw threaded side walls that cooperate with the screw threaded rod 906 such that rotation of the screw threaded rod causes the second fixing means 914 to slide along the fixed rod 905, thus compressing or stretching the object to be manipulated.

The device 900 includes a motor 922 (such as a stepper motor) and a coupling 924 for translating rotation of a rod 926 of the motor 922, which rod 922 is shown vertical in figure 9, to rotation of the screw threaded rod 906, which is shown horizontal in figure 9. The motor 922 may be held in place by one or more supports (not shown).

Thus, the motor 922 caii be fixed above the rest of the device 900. Therefore, the device 900 excluding the motor 922 can be lowered into a container containing fluid and held therein without damaging the motor 922. The motor 922 can still be used to rotate the screw threaded rod 906 and, consequently, move the second fixing means 914 towards or away from the end piece 902, depending on the direction in which the motor 922 is driven. Thus, the object can be manipulated whilst the device (excluding the motor 922) has been lowered into the container of fluid.

Alternative embodiments of the invention may have different dimensions to those specified and/or shown depending on the application of the cell manipulation device.

For example, where tendons are to be stretched, which may require larger forces than those applied to a biological sample, the dimensions of one or more components may tend to be larger for additional strength, and/or alternative materials for one or more components may be required for additional strength. * .

All of the features disclosed in this specification (including any accompanying claims, *5*S abstract and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and/or steps are mutually exclusive. 5* S

Each feature disclosed in this specification (including any accompanying claims, * *. ..* abstract and drawings), may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features.

The invention is not restricted to the details of any foregoing embodiments. The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed. The claims should not be construed to cover merely the foregoing embodiments, but also any embodiments which fall within the scope of the claims. S. S. * S.. S... * S I... S. * S * *5*

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Claims

1. A biological sample manipulation device, comprising: first fixing means for fixing to a first end of a biological sample; second fixing means for fixing to a second end of the biological sample; a screw-threaded rod arranged to cooperate with the first and/or second fixing means and be rotatable about its elongate axis to move the first fixing means relative to the second fixing means; and rotate means for rotating the screw-threaded rod.

2. A device as claimed in claim 1, wherein the rotate means comprises a stepper motor.

3. A device as claimed in claim 2, wherein the stepper motor can rotate the screw-threaded rod in 2048 steps per revolution of the screw-threaded rod.

4. A device as claimed in any of the preceding claims, wherein the screw : * threaded rod is arranged to be rotatable in a first direction to separate the first and second fixing means, and rotatable in a second direction to bring the first and second fixing means together. * * * ***

5. A device as claimed in claim 4, wherein the screw-threaded rod is arranged such that one revolution of the rod moves the first and second fixing means further apart or closer together by 0.5 mm.

S..... * 25

6. A device as claimed in any of the preceding claims, comprising a fixed rod on which the first fixing means is slidably mounted and on which the second fixing means is fixed.

7. A device as claimed in claim 6, wherein the screw-threaded rod rotates to slide the first fixing means along the fixed rod.

8. A device as claimed in claim 7, wherein the first fixing means includes a screw-threaded through hole for cooperating with the screw-threaded rod such that rotation of the screw-threaded rod causes the first fixing means to slide along the fixed rod.

9. A method as claimed in any of the preceding claims, comprising a substantially sealed case.

10. A method as claimed in claim 9, wherein the case comprises an elongate housing with an open end and a cap that cooperates releasably with the open end of the housing to substantially seal the open end of the housing.

11. A controller for controlling a cell manipulation device of claim 1.

12. A controller as claimed in claim 11, wherein the controller controls a plurality of cell manipulation devices as claimed in claim 1.

13. A controller as claimed in claim 11 or 12, wherein the controller controls the stepper motor such that the biological sample is stretched and/or compressed according to a profile. * * S...

14. A controller as claimed in claim 13 wherein the profile is specified by specifying an amount of stretch and/or compression and a rate of change.

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