Method and device for automatically determining the position of a microsystem for manipulating a spherical microobject

Abstract

In a method for automated determination of the relative position between a first hole on a first microsystem component, and a second hole on a second microsystem component, the two holes lie in a liquid medium. Under the supervision of a control device, the first and second microsystem components are displaced relative to one another into different relative positions. Electrical signals are delivered to one of the two microsystem components and are recorded on the other of the two microsystem components as measurement values which depend on the relative position of the two microsystem components with respect to one another. For different relative positions between the two microsystem components, measurement values are determined to determine that relative position in which the two microsystem components are positioned with respect to one another in such a way that their holes are mutually aligned.

1 - 17 . (canceled) 
     
     
         18 . A method for automated determination of the relative position between a first hole on a first microsystem component, which is preferably provided with a first channel opening in the first hole, and at least one second hole on a second microsystem component, which is preferably provided with a second channel opening in the second hole, wherein the first and second microsystem components are located in a liquid medium at least with the first and second holes immersed in said medium, comprising the steps:
 displacing the first and second microsystem components relative to one another into different relative positions by a control device controlled by a computer,   delivering electrical signals via one of the first and second microsystem components into the medium and recording on the other of the first and second microsystem components measurement values which depend on the relative position of the two microsystem components with respect to one another,   recording said measurement values for at least two different relative positions between the first and second microsystem components, and determining in the control device from said recorded measurement values a relative alignment position into which the first and second microsystem components are to be positioned with respect to one another in such a way that the first and second holes are mutually aligned.   
     
     
         19 . The method of  claim 18 , wherein the electrical signals are delivered into the medium by means of a signal electrode arranged in a first channel provided in the first microsystem component and opening in the first hole, and the measurement values are recorded by means of a measurement electrode arranged in a second channel provided in the second microsystem component and opening in the second hole. 
     
     
         20 . The method of  claim 19 , wherein the electrical signals delivered into the medium are voltage pulses having pulse amplitudes that are measured at the second microsystem component and provided as said measurement values. 
     
     
         21 . The method of  claim 18 , wherein the first and second holes each have a longitudinal axis, the first and second microsystem components are displaced with respect to one another along at least two mutually orthogonal spatial axes, the first of said two spatial axis extending approximately parallel to projections of the longitudinal axes of the first and second holes into a plane defined by said two spatial axes. 
     
     
         22 . The method of  claim 21 , wherein a rough estimate for said relative alignment position is determined along the first spatial axis by displacing the first and second microsystem components along the first spatial axis into at least two different relative positions while maintaining a fixed relative position along the second spatial axis and taking a measurement value for each relative position. 
     
     
         23 . The method of  claim 22 , wherein the fixed relative position along the second spatial axis is selected in such a way that there is a safety distance between the first and second microsystem components in the direction of the second spatial axis, which safety distance is determined as a function of the dimensions of the first and second microsystem components in the direction of the second spatial axis. 
     
     
         24 . The method of  claim 21 , wherein a rough estimate for said relative alignment position is determined along the second spatial axis by displacing the first and second microsystem components along the second spatial axis into at least two different relative positions while maintaining a fixed relative position along the first spatial axis and taking a measurement value for each relative position. 
     
     
         25 . The method of  claim 23 , wherein a rough estimate for said relative alignment position is determined along the second spatial axis by displacing the first and second microsystem components along the second spatial axis into at least two different relative positions while maintaining a fixed relative position along the first spatial axis and taking a measurement value for each relative position. 
     
     
         26 . The method of  claim 25 , wherein the fixed relative position along the first spatial axis is selected in such a way that there is a safety distance between the first and second microsystem components in the direction of the first spatial axis, which safety distance is determined as a function of the dimensions of the first and second microsystem components in the direction of the first spatial axis. 
     
     
         27 . The method of  claim 24 , wherein a finely resolved estimate for said relative alignment position is determined along the first spatial axis by displacing the first and second microsystem components along the first spatial axis into different relative positions while maintaining said rough estimate for said relative alignment position along the second spatial axis and taking a measurement value for each relative position. 
     
     
         28 . The method of  claim 26 , wherein a finely resolved estimate for said relative alignment position is determined along the first spatial axis by displacing the first and second microsystem components along the first spatial axis into different relative positions while maintaining said rough estimate for said relative alignment position along the second spatial axis and taking a measurement value for each relative position. 
     
     
         29 . The method of  claim 27 , wherein a finely resolved estimate for said relative alignment position is determined along the second spatial axis by displacing the first and second microsystem components along the second spatial axis into different relative positions while maintaining said finely resolved estimate for said relative alignment position along the first spatial axis and taking a measurement value for each relative position. 
     
     
         30 . The method of  claim 28 , wherein a finely resolved estimate for said relative alignment position is determined along the second spatial axis by displacing the first and second microsystem components along the second spatial axis into different relative positions while maintaining said finely resolved estimate for said relative alignment position along the first spatial axis and taking a measurement value for each relative position. 
     
     
         31 . The method of  claim 21 , wherein the first and second microsystem components are displaced relative to one another along a third spatial axis which extends orthogonally to the first and second spatial axes, a relative alignment position being determined in the third spatial axis by displacing the first and second microsystem components along the third spatial axis into at least two different relative positions while maintaining a fixed relative position along the first and second spatial axes and taking a measurement value for each relative position. 
     
     
         32 . The method of  claim 18 , wherein the first microsystem component is configured for immobilizing a biological cell and the second microsystem component is configured for contacting the cell immobilized in this way. 
     
     
         33 . The method of  claim 18 , wherein a third microsystem component having a third hole is provided, the third microsystem component preferably being mechanically connected in a fixed way to the first microsystem component, and wherein the relative position between the second and third holes is determined. 
     
     
         34 . A method for the automated contacting of at least one microscopic test object having a diameter and which is immobilized at a first hole on a first microsystem component and is then contacted through a second hole on a second microsystem component, wherein
 a relative alignment position between the first and second holes along a first and orthogonal second spatial axis is being determined by the method of  claim 18 ,   said microscopic test object is being immobilized on the first hole,   the first and second holes are being mutually aligned along said first spatial axis with a start distance between said first and second holes which corresponds to at least two times a maximum diameter of a microscopic test object to be contacted,   an electrical resistance in front of the second hole is being measured by means of a sensor electrode,   a search method is performed, wherein the distance between the first and second holes along the first spatial axis is reduced stepwise and the electrical resistance is measured again for each new distance,   the search method being finished, and the microscopic test object being evaluated as contacted, when there is a predetermined change in the measured resistance value between two subsequent measurements of the electrical resistance.   
     
     
         35 . The method of  claim 34 , wherein prior to mutually aligning the first and second holes along said first spatial axis in said start distance, said test object is being checked for its suitability for subsequent examinations. 
     
     
         36 . The method of  claim 34 , wherein the electrical resistance in front of the first hole is measured by means of a sensor electrode during the immobilization of the test object on the first hole. 
     
     
         37 . A device for the automated contacting of at least one microscopic test object which is immobilized on a first hole and is then contacted through a second hole, comprising
 at least one first microsystem component, on which the first hole is provided,   at least one second microsystem component, on which the second hole is provided,   a reaction vessel for holding a liquid medium, the first and second microsystem components being located in said liquid medium at least with the first and second holes immersed in said medium,   a mechanism, by means of which the first and second microsystem components are displaced relative to one another at least in two mutually orthogonal spatial directions,   a control device, by means of which the mechanism is controlled in an automated fashion, and   a measurement arrangement, by means of which electrical signals are delivered into said liquid medium via one of the first and second microsystem components and are recorded on the other of the first and second microsystem components to provide measurement values which depend on the relative position of the first and second microsystem components with respect to one another,   the control device being adapted to determine from recorded measurement values for at least two different relative positions a relative alignment position into which the first and second microsystem components are to be positioned with respect to one another in such a way that the first and second holes are mutually aligned.   
     
     
         38 . The device of  claim 37 , said first microsystem component being provided with a first channel opening into the first hole, and said second microsystem component being provided with a second channel opening into the second hole.