Method for analyzing chemical and/or biological samples by means of particle images

Abstract

A method for analyzing chemical and/or biological samples comprises the production of a particle image ( 42 ) of at least one particle included in the sample. Subsequently, a particle surface ( 10 ) of the at least one particle included in the particle image ( 42 ) is divided into particle zones ( 14,18 ). According to the invention, zone-dependent particle data are subsequently acquired in different states (z 1, z 2, z 3 ), which then can be evaluated.

The invention claimed is: 
     
       1. Method for analyzing chemical and/or biological samples with high-throughput or medium-throughput screening installations, comprising the steps of:
 producing one or more particle images of at least one sample with at least one particle, having a particle surface, being included in the sample; 
 defining several particle zones of the particle surface by determining a particle boundary before the particle zones are defined and defining a main point within the particle surface and boundary lines extending radially therefrom to the particle boundary, wherein the several particle zones of the particle surface are defined independent of subparticular compartments; 
 acquiring particle data of the sample in dependence on the particle zones; and 
 evaluating the acquired particle data. 
 
     
     
       2. Method according to  claim 1 , wherein a plurality of particle images are produced and at least one particle zone is defined that extends over several particle images of the plurality of particle images. 
     
     
       3. Method according to  claim 1 , wherein several particle images are produced of several samples. 
     
     
       4. Method according to  claim 1 , wherein the particle zones are defined within the particle surface of the at least one particle included in the particle image. 
     
     
       5. Method according to  claim 1 , wherein substantially the entire particle surface is divided into particle zones. 
     
     
       6. Method according to  claim 1 , wherein the particle zones are defined immediately before the acquisition of the particle data. 
     
     
       7. Method according to  claim 1 , wherein several particle images are produced of the at least one sample at different points of time. 
     
     
       8. Method according to  claim 7 , wherein different states of the at least one particle included in the sample are compared with each other when evaluating the acquired particle data. 
     
     
       9. Method according to  claim 1 , wherein samples of different particle states are analyzed at different times. 
     
     
       10. Method according to  claim 1 , wherein the sample is colored before the particle image is produced. 
     
     
       11. Method according to  claim 1 , wherein the boundary lines extending radially from the main point to the particle boundary define first, second and third particle zones. 
     
     
       12. Method according to  claim 1 , wherein the most luminous point within the particle surface is defined as the main point. 
     
     
       13. Method according to  claim 1 , wherein the radially extending boundary lines have a substantially identical aperture angle with respect to each other. 
     
     
       14. Method according to  claim 1 , wherein each individual particle zone of the several particle zones is defined so that each individual particle zone has substantially the same surface area as each of the other individual particle zones. 
     
     
       15. Method according to  claim 1 , wherein individual particle zones of the several particle zones are selected for analysis in dependence on selection criteria. 
     
     
       16. Method according to  claim 8 , wherein particle data acquired in dependence on the particle zones includes size of the particle zones in different states of the at least one particle. 
     
     
       17. Method according to  claim 8 , wherein particle data acquired in dependence on the particle zones includes luminosity of the particle zones in different states of the at least one particle. 
     
     
       18. Method according to  claim 1 , wherein the at least one particle is a cell and particle zones, independent of subcellular compartments, are defined. 
     
     
       19. Method according to  claim 18 , wherein the cell forms part of a cell compound comprising one or more cells. 
     
     
       20. Method according to  claim 18 , wherein samples of different cell states are analyzed and the cell state comprises one or more of components selected from the group consisting of apoptosis, necrosis, translocation of cellular components, internalization of membranous molecules or molecule complexes, cell differentiation, morphological appearance, splitting of subcellular compartments and generation of cellular compartments. 
     
     
       21. Method according to  claim 20 , wherein the cell state is influenced by adding chemical substances, biological substances, or chemical and biological substances. 
     
     
       22. Method according to  claim 21 , wherein the cell state is influenced by adding potential pharmacological active substances. 
     
     
       23. Method according to  claim 1 , wherein the particle surface is divided into at least five particle zones. 
     
     
       24. Method according to  claim 23 , wherein the particle surface is divided into at least ten particle zones. 
     
     
       25. Method according to  claim 1 , further comprising the steps of:
 presetting a threshold value for defining a boundary between background and foreground in the one or more particle images; and 
 defining the particle surface by a difference between the background and the foreground that exceeds the threshold value. 
 
     
     
       26. Method for analyzing chemical and/or biological samples, particularly with high-throughput or medium-throughput screening installations, comprising the steps of:
 (a) producing one or more particle images of at least one sample, with at least one particle having a surface included in the sample;   (b) defining several particle zones, wherein boundary lines of the particle zones have substantially geometrically similar shapes and wherein the several particle zones of the particle surfaces are defined independent of subparticular compartments, and wherein each particle zone is defined by an inner boundary line and an outer boundary line, wherein each of the inner boundary line and the outer boundary line has a substantially constant distance to a boundary of the at least one particle and at least two particle zones are adjacent to each other, and wherein a particle boundary is determined before the particle zones are defined;   (c) acquiring particle data of the sample in dependence of the zones; and   (d) evaluating the acquired particle data.    
     
     
       27. Method according to claim 26, wherein the substantially geometrically similar shapes are arranged concentrically with respect to each other to define particle zones.  
     
     
       28. Method according to claim 26, wherein a plurality of particle images are produced and at least one particle zone is defined that extends over several particle images of the plurality of particle images.  
     
     
       29. Method according to claim 26, wherein several particle images are produced of several samples.  
     
     
       30. Method according to claim 26, wherein the particle zones are defined within a particle surface of the at least one particle included in the particle image.  
     
     
       31. Method according to claim 26, wherein substantially the entire particle surface is divided into particle zones.  
     
     
       32. Method according to claim 26, wherein outer zones arranged outside the particle surface are defined.  
     
     
       33. Method according to claim 26, wherein at least one particle zone is defined that extends over parts of the particle surface and over a surface lying outside the particle surface.  
     
     
       34. Method according to claim 26, wherein the definition of the particle zones takes place in time before acquisition of the particle image.  
     
     
       35. Method according to claim 26, wherein the particle zones are defined immediately before acquisition of the particle data.  
     
     
       36. Method according to claim 26, wherein several particle images are produced of one sample at different points of time.  
     
     
       37. Method according to claim 36, wherein different states of the at least one particle included in the sample are compared with each other when evaluating the particle data.  
     
     
       38. Method according to claim 26, wherein samples of different particle states are analyzed at different times.  
     
     
       39. Method according to claim 26, wherein the sample is colored before the particle image is produced.  
     
     
       40. Method according to claim 26, wherein the individual zones are determined such that the individual zones each have the same surface area.  
     
     
       41. Method according to claim 26, wherein individual particle zones are selected depending on selection criteria.  
     
     
       42. Method according to claim 26, wherein the size of the particle zones, in different states, is determined as particle data.  
     
     
       43. Method according to claim 26, wherein luminosity of the particle zones, in different states, is determined as particle data.  
     
     
       44. Method according to claim 26, wherein the at least one particle is a cell and zones independent of subcellular compartments are defined.  
     
     
       45. Method according to claim 44, wherein the cell forms part of a cell compound.  
     
     
       46. Method according to claim 26, wherein samples of different cell states are analyzed and the cell state comprises one or more states selected from the group consisting of apoptosis, necrosis, translocation of cellular components, internalization of membranous molecules or molecule complexes, cell differentiation, morphological appearance, splitting of subcellular compartments and generation of cellular compartments.  
     
     
       47. Method according to claim 46, wherein the cell state is influenced by adding a chemical substance, or a biological substances, or the chemical substance and the biological substance.  
     
     
       48. Method according to claim 46, wherein the cell state is influenced by adding one or more potential pharmacological active substances.  
     
     
       49. Method according to claim 26, wherein the surface of the at least one particle is entirely divided into the several particle zones, wherein each particle zone is immediately adjacent to another particle zone without any clearance.