PIEZOELECTRIC MICROPIPETTE

Abstract

The invention relates to a piezoelectric micropipette, which comprises a capillary tube forming the pipette, and an expansion chamber connected to the capillary tube, the expansion chamber having a flexible element and being connected to a piezoelectric actuator. According to the invention the flexible element of the micropipette is arranged in the expansion chamber, and the flexible element is connected to a rigid displacing element, and a piezoelectric actuator is connected to the rigid displacing element.

Claims

1. Piezoelectric micropipette comprising a capillary tube (1) forming the pipette, and an expansion chamber (2) connected to the capillary tube (1), the expansion chamber having a flexible element and being connected to a piezoelectric actuator (5) characterised in that the flexible element is a flexible element (3) arranged in the expansion chamber (2), the flexible element is connected to a rigid displacing element (4), and a piezoelectric actuator (5) is connected to the rigid displacing element (4).

2. Micropipette of claim 1, wherein the expansion chamber (2) has a substantially cylindrical shape, the flexible element arranged in the expansion chamber is configured as an O-ring (3), and the rigid displacing element (4) is configured as a pressing plate having the form of a substantially circular disc.

3. Micropipette of claim 2, wherein the O-ring (3) arranged in the expansion chamber (2) is an O-ring (3) having a size that can be selected arbitrarily in a range of dimensions between a minimum and a maximum dimension, and can be replaced if necessary, wherein the cylindrical expansion chamber (2) is configured for receiving an O-ring (3) of different sizes, and the inner diameter of the cylindrical side wall of the expansion chamber substantially corresponds to the outer diameter of the largest O-ring (3).

4. Micropipette of claim 3, wherein the surface of the cylindrical expansion chamber (2) contacting the O-ring (3) is a substantially planar surface.

5. Micropipette of claim 3, wherein the surface of the cylindrical expansion chamber (2) contacting the O-ring (3) is provided with concentric grooves for positioning the O-rings (3) concentrically.

6. Micropipette of claim 1, wherein the capillary tube (1) forming the pipette is releasably connected to the expansion chamber (2) through the pipette holder (7), wherein a capillary bore (1a) is formed in the pipette holder for connecting the capillary tube (1) with the expansion chamber (2).

7. Micropipette of claim 1, wherein the expansion chamber (2) is arranged in a rigid housing forming the pipette holder (7), which can be closed by a releasably connected closing member (6).

8. The micropipette of claim 7, wherein the closing member (6) is formed by the housing, which is holding the piezoelectric actuator (5) and which is provided with a chamber for receiving the piezoelectric actuator (5).

9. The micropipette of claim 7, wherein the closing member (20) is configured for filling the micropipette, and which is provided with an inlet connecting element (21).

10. The micropipette of claim 7, wherein the capillary tube (1) forming the pipette is fixed to the pipette holder (7) with a releasable fixing element, preferably a threaded fixing element (12).

11. The micropipette of claim 10, wherein in the pipette holder (7) a receiving chamber is formed for receiving the capillary tube (1) forming the pipette.

12. The micropipette of claim 11, wherein in the pipette holder (7) the receiving chamber for receiving the capillary tube (1) forming the pipette is also provided with at least one sealing and/or fixing element (8, 9) between the capillary tube (1) and the wall of the receiving chamber.

13. The micropipette of claim 12, wherein, in the receiving chamber in the pipette holder for receiving the capillary tube (1) forming the pipette, one of the sealing and/or fixing elements is a conical sealing and/or fixing element (8) and the other sealing and/or fixing elements is configured as an O-ring (9).

14. The micropipette of claim 13, wherein in the pipette holder (7) the receiving chamber (2) for receiving the capillary tube (1) forming the pipette is also provided with a guiding sleeve (10) between the conical sealing element (8) and the O-ring (9) for fixing and guiding the capillary tube (1).

15. The micropipette of claim 13, wherein in the pipette holder in the receiving chamber (2) for receiving the capillary tube (1) forming the pipette, the guiding sleeve (10) for holding and guiding the capillary tube between the conical sealing member (8) and the O-ring (9), has an end section in proximity of the conical sealing member (8) with a conical shape corresponding to the conical shape of the conical sealing element (8) and has an end face in proximity of the O-ring (9) with an at least partly planar surface substantially perpendicular to the longitudinal direction.

16. The micropipette of claim 10, wherein a lighting means is connected to the pipette fixing and retaining element (12).

17. The micropipette of claim 16, wherein a lighting means is a LED lighting means.

18. The micropipette of claim 17, wherein the lighting means has a circular carrier plate (13) with LED lighting elements (15) arranged in at least one concentric circle.

19. The micropipette of claim 18, wherein the LED lighting elements (15) in the lighting means are arranged and configured for phase contrast illumination.

20. The micropipette of claim 1, wherein the micropipette is mounted on a robotic arm, which enables a programmed movement of the micropipette between the desired spatial positions.

Description

SHORT DESCRIPTION OF THE DRAWING

[0025] Examples of embodiments of the invention are described in more detail hereinafter with reference to the accompanying drawings wherein:

[0026] FIG. 1 is a side view of the piezoelectric micropipette according to one aspect of the invention,

[0027] FIG. 2 is a cross sectional side view of the piezoelectric micropipette of FIG. 1,

[0028] FIG. 3 is a bottom view of the piezoelectric micropipette of FIG. 1 with a lighting means,

[0029] FIG. 4 is a side view of a piezoelectric micropipette with a filling inlet connecting element,

[0030] FIG. 5 is a cross sectional side view of a piezoelectric micropipette of FIG. 4, with a filling inlet connecting element,

[0031] FIG. 6 is a cross sectional side view of a piezoelectric micropipette with a pipette tip illuminated by the lighting elements,

[0032] FIG. 7 is a cross sectional side view of a piezoelectric micropipette with a filling inlet connecting element and a pipette tip illuminated by the lighting elements,

[0033] FIG. 8 is an enlarged view of the expansion chamber and the surrounding elements of the micropipette according to the invention, and

[0034] FIG. 9 is an enlarged view of the pipette holder and connected components of the piezoelectric micropipette.

DESCRIPTION OF THE EMBODIMENTS OF THE INVENTION

[0035] FIG. 1 is a side view of the piezoelectric micropipette according to one aspect of the invention, with a capillary tube 1 forming the pipette, a housing 6 for receiving a piezoelectric actuating element, a pipette holder 7, a threaded fixing element 12, a holding plate 13 and a cover 11. The front side of the housing 6 is provided with a fixing surface 16 with fixing screws 18. In this embodiment a spring 14 is arranged between the fixing element 12 and the holding plate 13. The spring 14 urges the holding plate 13 comprising the LED lighting elements in a downward direction. In this manner the vertical position of the lighting elements is stabilized. The holding plate 13 is fixed by a threaded nut, which is also used for adjusting the height of the illuminating plate. The spring thereby presses the holding plate 13 against the nut.

[0036] The fixing surface 16 can be used for fixing the piezoelectric micropipette of the invention on a robotic arm which is movable along at least one coordinate and which enables a program controlled movement of the piezoelectric micropipette in space between desired positions so that the system can also be configured and used for automatic pipetting.

[0037] FIG. 2 shows a cross sectional side view of the piezoelectric micropipette of FIG. 1. As it is clear from the drawing, the upper end of the capillary tube 1 is arranged in a pipette holder 7. In the pipette holder 7, coaxially with the capillary tube 1, a capillary bore 1a is formed which communicates with a preferably cylindrical expansion chamber 2. In the expansion chamber 2 a flexible element 3 is arranged in the form of an O-ring, which is mechanically contacted by a rigid displacing element 4 which is formed as a pressing plate in the form of a circular plate or disk. The rigid displacing element 4 is connected to a piezoelectric actuator 5 which is arranged in a housing 6. The housing 6 is mechanically connected to the pipette holder 7. In order to establish the mechanical connection, the housing 6 is provided with an internal thread and the pipette holder 7 is provided with an external thread.

[0038] The expansion chamber 2 is thereby terminated by the upper end face of the pipette holder 7, the O-ring 3 arranged in the expansion chamber 2, and the rigid displacing element 4. The dimension of the O-ring 3 arranged in the expansion chamber 2 can be selected in a range of dimensions between a minimum dimension and a maximum dimension. Further, the O-ring can be replaced if necessary. The cylindrical expansion chamber 2 is preferably configured for receiving O-rings 3 of different dimensions, wherein the inner diameter of the cylindrical side wall of the expansion chamber 2 corresponds to the outer diameter of the largest selectable O-ring 3.

[0039] The expansion chamber 2 is provided by a cylindrical recess formed in the upper end of the pipette holder 7 and serves for receiving the O-ring 3, and has a substantially plane contact surface for the O-ring 3.

[0040] In a preferred embodiment of the micropipette of the invention, the substantially plane contact surface for the O-ring 3 in the expansion chamber 2 is provided with concentric grooves (not shown) for concentric positioning of the O-rings 3 of different dimensions.

[0041] The upper end of capillary tube 1 can be inserted into and arranged in the cylindrical receiving chamber of the pipette holder 7. In order to enable a correct positioning of the capillary tube 1, upper and lower sealing and/or fixing elements 8 and 9 are inserted and arranged in the receiving chamber. As shown in FIG. 2, a conical sealing 8 element can be arranged at the upper end of the capillary tube 1. The conical sealing element has a planar upper end face for contacting the substantially planar contact surface of the upper end of the cylindrical receiving chamber, and a lower conical outer surface for contacting a conical inner surface on the upper end of a guiding sleeve 10 for guiding the capillary tube 1. The conical outer contact surface at the lower end of the conical sealing 8 element tapers in downward direction and the conical inner contact surface of the guiding sleeve 10 expands correspondingly in the upward direction. The conical sealing element 8 and the conical end face of the guiding sleeve 10 have similar cone angles. The conical sealing element 8 is used for sealing, fixing and positioning the upper end of the capillary tube 1 with high precision coaxially with the capillary bore 1a of the pipette holder 7. The lower end of the guiding sleeve 10 is terminated by a planar surface substantially perpendicular to the longitudinal direction, and is contacted by a lower sealing and fixing element being configured as an O-ring 9. The O-ring 9 is secured by a fixing and retaining element 12 which can be releasably connected to the pipette holder 7 and it is used for pressing the O-ring 9 to the planar end face of the guiding sleeve 10. The fixing and retaining element 12 is preferably a threaded component, which in the shown embodiment is provided with an external threading for connecting an internal threaded portion at the lower end of the pipette holder 7. The fixing and retaining element 12 has an upper threaded portion, a lower threaded portion and a middle portion extending in a cross direction. The lower threaded portion can receive a holding plate 13 for holding lighting means.

[0042] A piezoelectric actuator 5 can be arranged in a receiving chamber of a housing 6, which can be attached releasably to the pipette holder 7. For this purpose, the housing may be provided with an internal threaded portion and can serve as a closing member. The piezoelectric actuator 5 may be supplied with a DC control voltage, upon which it is compressed or expanded in the longitudinal direction. The control voltage of the piezoelectric actuator 5 may be introduced through an opening in the cover 11 of the housing 6 by means of a not shown voltage source cable. Due to the change of the longitudinal dimension of the piezoelectric actuator 5 the O-ring 3 located in the expansion chamber 2 will be compressed to a different extent, which results at the same time in a change of the volume of the expansion chamber 2. On the other hand, the volume change of the expansion chamber 2 will result in a take up or release of liquid present in the capillary tube 1 and the capillary bore 1a.

[0043] FIG. 3 shows a lighting means to be used in connection with the piezoelectric micropipette of the invention, which can be preferably formed as a LED lighting means. As it is shown in FIG. 3, the lighting means has a preferably circular holding plate 13 with LED lighting elements 15 arranged in at least one concentric circle. The LED lighting elements 15 provide for a proper illumination of the tip of the pipette, which may be advantageous especially when microscopic images are taken. In certain applications it may be advantageous to arrange and configure the LED lighting elements 15 for providing phase contrast illumination. As shown in the drawing, the LED lighting elements 15 are arranged in four (two pairs of) concentric circles with predefined different dimension.

[0044] The pipette holder 7 of the micropipette is connected releasably, in the present embodiment by means of a threaded connection, to the housing 6 which receives the piezoelectric actuator 5, and thus the housing 6 can be removed and replaced by a closing member 20 connecting with a threaded portion to the pipette holder 7 as shown in FIGS. 4 and 5. The threaded closing member 20 is provided at the upper end with a filling inlet 21, which can be connected e.g. to a standard syringe for filling the micropipette with a liquid. The accurate operation of the micropipette requires that the whole inner volume of the micropipette is filled bubble-free with a liquid. As gases are compressible, the eventually remaining bubbles can degrade the dispensing accuracy of the micropipette. During filling of the micropipette of the invention, the O-ring 3 in the expansion chamber 2 is replaced by another O-ring 22 for filling purposes. The filling head consisting of the closing member 20 and the filling inlet 21 is only needed for filling and eventually a cleaning process in connection with the micropipette. Before the first use of a new micropipette, which is free from any liquid (dry state), the micropipette has to be filled through the filling head entirely and bubble-free with a liquid appropriate for the sample taking process, e.g. with water. After finishing the sample taking process, the micropipette is preferably emptied and washed and also the washing liquid is emptied. As the parts of the micropipette of the inventions are designed to be assembled and disassembled, the individual components can be separately cleaned, sterilized or simply replaced.

[0045] FIGS. 6 and 7 illustrate the beams of light emitted by the lighting means of the micropipette of the invention. FIG. 3 shows a bottom view of the LED lighting elements 15 which are arranged in four concentric circles such that the individual circles of LED lighting elements 15 and the tip of the capillary tube 1 define a predetermined cone angle. The cone angles of an inner circle and an outer circle of a circle pair in the shown embodiment are 15 degree and 30 degree, respectively. The diameter of the concentric circles is determined so that the light beams of the LED lighting element 15 of an inner circle and an outer circle of a circle pair intersect at the tip of the capillary tube 1, and the light beams of the LED lighting elements 15 of an inner circle and an outer circle of another circle pair intersect at a predetermined distance from the tip of the capillary tube 1. The predetermined distance in the shown embodiment is 20 mm. Such an arrangement is necessary for phase contrast microscopic imaging of a sample at the tip of the capillary tube 1 or 20 mm below that.

[0046] The function of the piezoelectric micropipette of the invention will now be described in more detail with reference to FIG. 8, depicting the expansion chamber 2, the O-ring 3, the pressing plate 4 and the piezoelectric actuator 5 in an enlarged view. Below we will provide the mathematical formula for the calculation of the volume of liquid which can be delivered with the piezoelectric micropipette of the invention.

[0047] The calculations are made under the condition that the O-ring has a dimension of 1×1 mm, which is one of the smallest size available on the market. As it is verified by the result of the calculations, the smallest amount of liquid is delivered with the smallest sized O-ring, and the largest dispensing accuracy can be achieved with the piezoelectric actuator having the smallest moving range or stroke.

[0048] Having an O-ring which is terminated by two parallel plates, the enclosed volume can be calculated as follows:

V=(D/2+d/2).sup.2*Pi*H=Pi mm.sup.3≈3.14 microlitre.

with D=1 mm (diameter of the opening of the O-ring)
d=1 mm (thickness of the O-ring)
H=1 mm (thickness of the O-ring)

[0049] The above volume V however still comprises half of the volume of the O-ring, because we have calculated the volume of a cylindrical space between the plates within the contact line with the O-ring. The volume of the O-ring (torus): v=2*Pi.sup.2*D/2*(d/2).sup.2=(Piz)/4 microlitre

[0050] Finally we obtain the volume of liquid enclosed by the O-ring: V−v/2=Pi−(Pi.sup.2)/8≈1.9 mm.sup.3 (microlitre)

[0051] The enclosed liquid volume in the expansion chamber 2 is therefore 1.9 microlitre, or about 2 microlitre.

[0052] Under the condition that the volume of the O-ring does not change and the compression deformation is symmetric, the liquid volume change is the following: DeltaH*(D/2+d/2).sup.2*Pi-DeltaH*Pi (microlitre)

[0053] The maximum longitudinal movement (DeltaH_max) of the piezo-element used in the example is 5 micrometre and the accuracy is about 1 nanometre. Therefore the piezo-element is capable of delivering about 15 nanolitre liquid. The dispensing accuracy is about 3 picolitre.

[0054] When using a piezo-element with a smaller stroke, the maximum volume of delivery is reduced and the dispensing accuracy is increased. A positioning accuracy of 0.1 nanometre or even better can be achieved with a piezo-element. When using the above O-ring it means an accuracy of 0.3 picolitre.

[0055] In the examples of the invention it is preferred to use piezo-elements with DC control and unipolar control circuit in order to avoid hysteresis caused by a pole change. The voltage-displacement curve of the piezo-elements, even in that case, is not completely linear, therefore an advance calibration might be necessary. In practical applications of the invention we have used a piezo-element of the type PICMA® P882 and P888.

[0056] The main advantages of the piezoelectric micropipette are the possibility of electrical control, the speed, the simple construction and the cost efficient application. The micropipette of the invention can be used with both transmitted and reflected light imaging, practically on an inverted microscope. It is also compatible with the microscopic imaging where the optical axis is coaxial with the axis of the micropipette. The surface of the micropipette contacting the liquid sample is entirely of inert material: the capillary tube is made of glass, the pipette holder, the expansion chamber and the pressing plate is made of stainless steel or plastic, the O-ring and the conical sealing is made of gum or Teflon® (PTFE).

LIST OF REFERENCES

[0057] 1 capillary tube (micropipette) [0058] 1a capillary bore [0059] 2 expansion chamber [0060] 3 O-ring [0061] 4 rigid displacing element, pressing plate [0062] 5 piezoelectric actuator [0063] 6 housing for piezoelectric actuator, closing member [0064] 7 pipette holder [0065] 8 conical sealing [0066] 9 O-ring [0067] 10 guiding sleeve [0068] 11 cover [0069] 12 (threaded) retaining element [0070] 13 holding plate [0071] 14 spring [0072] 15 lighting element, LED [0073] 16 fixing surface [0074] 17 recess [0075] 18 screw [0076] 20 closing member [0077] 21 filling inlet [0078] 22 O-ring