Biochip for the archiving and medical laboratory analysis of biological sample material

Abstract

A biochip for diagnostic purposes comprises a sample carrier made of a solid matrix, on the surface of said sample carrier is bound the sample material to be analysed which originates from a biological organism.

1 . Biochip for diagnostic purposes, comprising a sample carrier of a solid matrix, to the surface of which is bound the sample material which is to be analysed and which originates from a biological organism.  
     
     
         2 . Biochip according to  claim 1 , characterized in that the biological sample material is bound directly to the surface of the matrix of the sample carrier, with the matrix or surface of the sample carrier preferably being pretreated by chemical or physical methods in order to improve the binding capacity of the surface for the sample material.  
     
     
         3 . Biochip according to  claim 1  or  2 , characterized in that each single specimen of the biochip has bound to its surface sample material from an individual biological organism, preferably from an individual patient.  
     
     
         4 . Biochip according to  claims 1  to  3 , characterized in that the biological material bound to the surface are body liquids, preferably whole blood, plasma, serum, urine, ascites, amniotic water, saliva, liquor, lavage material from body cavities or bronchoalveolar lavage, or tissue samples or organ samples, or components, cells, fractions, concentrates or extracts from the liquids or tissue or organ samples mentioned.  
     
     
         5 . Biochip according to any of the preceding claims, characterized in that the surface of the sample carrier is subdivided into micro-areas, preferably at least 100 microareas per cm 2 , said micro-areas preferably being configured as depressions, or being separated from one another by hydrophobic or non-wettable border regions.  
     
     
         6 . Sample carrier made of a solid matrix, characterized in that it has a surface suitable for binding biological material, and in that it is suitable for producing a biochip according to  claim 1 .  
     
     
         7 . Sample carrier according to  claim 6 , characterized in that the surface suitable for binding biological material is subdivided into micro-areas.  
     
     
         8 . Sample carrier according to  claim 7 , characterized in that the sample carrier preferably has at least 100 microareas per cm 2 , and that the micro-areas are configured as depressions or are separated from each other by hydrophobic or non-wettable border areas.  
     
     
         9 . Biochip according to any one of  claims 1  to  5 , or sample carrier according to any one of  claims 6  to  8 , characterized in that the surface area of the biochip or sample carrier is maximally 10 cm 2 , preferably maximally 4 cm 2 , the sample carrier preferably being configured as a flat-shaped body, especially preferred with a square or rectangular outline, and the thickness of the flat-shaped sample carrier preferably being less than 3 mm, especially preferred less than 1 mm.  
     
     
         10 . Biochip or sample carrier according to any one of the preceding claims, characterized in that the matrix or the surface of the sample carrier is pre-treated by chemical or physical methods, or that the surface of the sample carrier has been enlarged by chemical or physical pre-treatment.  
     
     
         11 . Biochip or sample carrier according to any one of the preceding claims, characterized in that, to improve the binding of the sample material to the said surface, the surface of the sample carrier is coated with a linker layer by means of which the sample material is bound.  
     
     
         12 . Biochip or sample carrier according to  claim 11 , characterized in that the linker layer is composed of linker molecules which enable the selective binding or concentration of specific groups of biological macromolecules, preferably proteins, peptides, glycoproteins, sugars, lipids or nucleic acids, or the binding or concentration of cells or specific cell types or cell populations, with different surface portions of the linker layer preferably containing different types of linker molecules.  
     
     
         13 . Biochip or sample carrier according to  claim 11  or  12 , characterized in that the linker layer on the surface of the sample carrier is configured so as to be discontinuous, with micro-areas of linker-containing surfaces and intermediate linker-free zones being formed, and with preferably at least 100 micro-areas per cm 2  being present.  
     
     
         14 . Biochip or sample carrier according to any one of the preceding claims, characterized in that it is equipped with means enabling the identification of the biochip or the storage of patient-related data, or the storage of analysis data, preferably by means of machine-readable bar codes, a machine-readable magnetic strip, a digital storage element or another machine-readable storage medium.  
     
     
         15 . Process for the production of a sample carrier according to  claim 6 , characterized in that sheet-like matrix raw material is mechanically separated, so that surface pieces with dimensions suitable for biochips result, or that the matrix raw material is liquefied and is subsequently cast into corresponding moulds using casting methods, preferably injection moulding.  
     
     
         16 . Process according to  claim 15 , characterized in that the surface of the sample carrier thus obtained is subdivided into micro-areas, said subdivision being achieved by 
 a) physical treatment of the surface, or    b) chemical treatment of the surface, or    c) printing methods, or    d) application of linker molecules in the area of the micro-areas, using a pipetting robot.    e) by a combination of at least two of the methods mentioned above.    
     
     
         17 . Diagnostic detection method comprising the following steps: 
 a) obtaining biological sample material, in the form of body fluids or tissue samples, from the organism to be examined;    b) making a biochip by binding the sample material to the surface of the sample carrier by coating with the liquid or suspended sample material obtained from body fluids or cell or tissue samples, and subsequent drying    c) applying specific, diagnostic detection reagents to single micro-areas of the biochip, using a pipetting robot, and incubation under the conditions suitable for the relevant detection reaction,    d) applying wash liquids to suppress unspecific reactions, and subsequent drawing-off of these wash liquids,    e) if necessary, repeating steps c) and d);    f) detection of measurement signals from positively reacting micro-areas;    g) computer-aided evaluation of the measurement data as well as storage of the measurement data.    
     
     
         18 . Method according to  claim 17 , characterized in that in step a) the biological sample material is prepared prior to its binding to the surface of the sample carrier, preferably by centrifugation, cell disintegration or extraction.  
     
     
         19 . Method according to  claim 17 , characterized in that steps c) to g) are performed on more than one biochip parallelly or simultaneously.  
     
     
         20 . Method according to  claim 17 , characterized in that the individual micro-areas of a biochip are, simultaneously or sequentially, treated with different specific diagnostic detection reagents.  
     
     
         21 . Method according to  claim 17 , characterized in that the specific diagnostic detection reagents utilized in step c) preferably are antibodies, antigens, lectins, DNA-probes, biomolecule-binding dyes or other specifically binding molecules.  
     
     
         22 . Method according to  claim 17 , characterized in that the detection of measurement signals takes place utilizing CCD-cameras, phototransistors, or radioactivity, fluorescence or luminescence detectors.  
     
     
         23 . Method according to  claim 17 , characterized in that the same biochip which is coated with the sample material of a certain patient is subjected to an analysis according to steps c) to f) or c) to g), either twice or several times in succession, with the biochip being stored during the period between the successive analyses, and with different micro-areas of the biochip being treated with detection reagents in the successive analyses.  
     
     
         24 . Use of the biochip or the sample carrier according to any one of the  claims 1  to  14 , or of a process according to steps a) and b) of claims  17  or  18 , for diagnostic detection reactions and/or for storing and archiving of sample material collected from patients.  
     
     
         25 . Use according to  claim 24 , for storing and archiving of patient sample material for purposes of routine diagnostics of patient samples, clinical research, or in epidemiological studies, for quality assurance and quality checks in blood banks, companies or other organisations, or in tumour diagnostics, or for forensic purposes.  
     
     
         26 . Use of a process according to claims  17 - 23 , for medicinal or veterinary purposes, for tumour diagnostics, for tumour marker analysis, in clinical research, for quality assurance in blood banks, companies or other enterprises, for epidemiological studies, for tissue typing, or for forensic purposes.