Image acquisition method and image acquisition system

Abstract

The present invention refers to an image acquisition method, comprising, in particular in a repeating, continuous, conditional closed-loop and / or conditional feedback manner, processes of capturing one or plural images of or from a sample carrier supported on a microscopy arrangement by using an optical engine (20), analyzing one or plural of already captured images and deriving imaging status data therefrom by using one or plural image analyzer units (30), comparing said derived imaging status data with predefined imaging target data and obtaining a comparison result, based on the comparison result, deriving setting data and / or a setting command, in particular designed for setting the optical engine (20), and depending on the comparison result and / or based on the setting data and / or the setting command conditionally setting the optical engine (20) and / or its operation for further images to be captured. Also, an image acquisition system (1) as suggested, which is configured to capture one or plural images of or from a sample carrier supported in or on a microscopy arrangement and to perform, use and / or to be used in the image acquisition method.

Description

[0001] IMAGE^ACQUISITION^METHOD^AND^IMAGE^ACQUISITION^SYSTEM Description The^present^invention^refers^to^an^image^acquisition^method^to^an^image^acquisition^system. Nowadays,^the^acquisition^and^analysis^of^multiple^images^in^life^sciences^and^in^particular^in^the^ technical^field^of^analyzing^biological^samples^becomes^more^and^more^important^in^particular^in^connection^ with^ the^ application^ of^ microscopy^ setups^ and^ in^ connection^ with^multiple^ samples^under^ the^ influence^ of^ multiple^ and^ changing^ incubation^ conditions^ and / or^ the^ exchange^ of^reagents. A^problem^of^known^devices^and^methods^in^this^regard^arises^from^the^risk^that^(i)^-^during^the^capture^of^multiple^ images^under^ changing^ conditions^ -^ the^ imaging^ conditions^may^ change,^ too,^and^(ii)^that^the^changing^conditions^may^lead^to^imaging^errors^which^cannot^be^considered^during^ an^automatic^imaging^procedure. It^is^an^object^underlying^the^present^invention^to^suggest^an^image^acquisition^method^and^system,^ which^are^configured^to^inherently^take^into^account^changing^imaging^conditions^and^in^particular^ imaging^errors^that^might^occur,^if^applicable,^with^correcting^countermeasures. The^object^underlying^the^present^invention^is^achieved^by^an^image^acquisition^method^according^to^ independent^ claim^ 1^ and^ by^ an^ image^ acquisition^ system^ according^ to^ independent^ claim^ 6.^Preferred^embodiments^of^the^present^invention^are^defined^in^the^respective^dependent^claims. According^to^a^first^aspect^of^the^present^invention,^an^image^acquisition^method^is^proposed^which^comprises,^ in^ particular^ in^ a^ repeating,^ continuous,^ conditional^ closed-loop^ and / or^ conditional^feedback^manner,^processes^of:- capturing^ one^ or^ plural^ images^ of^ or^ from^ a^ sample^ carrier^ supported^ on^ a^ microscopy^arrangement^by^using^an^optical^engine^20,- analyzing^one^or^plural^of^already^captured^images^and^deriving^imaging^status^data^therefrom^by^using^one^or^plural^image^analyzer^units^30,- comparing^said^derived^imaging^status^data^with^predefined^imaging^target^data^and^obtaining^a^ comparison^result,- based^on^the^comparison^result,^deriving^setting^data^and / or^a^setting^command,^in^particular^designed^for^setting^the^optical^engine^20,^and- depending^ on^ the^ comparison^ result^ and / or^ based^ on^ the^ setting^ data^ and / or^ the^ setting^command^conditionally^setting^the^optical^engine^20^and / or^its^operation^for^further^images^to^ be^captured. Due^to^the^comparison^process,^differences^between^target^image^data^in^image^data^in^connection^with^an^actually^acquired^ image^can^be^classified^as^belonging^ to^an^ image^error,^ if^applicable,^ in^order^to^design^suitable^countermeasures,^e.g.^in^the^sense^of^a^closed^loop^feedback^process. According^to^a^preferred^embodiment^of^the^present^invention,^the^process^of^analyzing^said^one^or^plural^ captured^ images^ is^ configured^ to^ identify^ the^presence^ or^ absence^of^ an^ image^ artifact,^ in^particular^with^respect^to^the^presence^or^absence^of^at^least^one^(i) of^bubbles^of^an^underlying^immersion^fluid,(ii) of^a^misalignment^of^a^sample^carrier^in^the^underlying^microscopy^arrangement,(iii) of^a^misalignment^of^a^sample^or^specimen^on^a^sample^carrier,^and(iv) of^detachment^of^a^sample^or^specimen^or^a^part^thereof^from^a^sample^carrier.Further^additionally^or^alternatively,^the^setting^data^and / or^the^setting^command^comprise^at^least^ one^(a) of^positioning^or^repositioning^of^one^or^plural^first^stage^units^22^for^positioning^the^sample^or^specimen^carrier^ in^a^ longitudinal^or^ length^direction^x,^X^and / or^a^ transversal^or^width^direction^y,^Y,(b) of^positioning^or^ repositioning^of^ one^or^plural^ second^ stage^units^23-1^ for^positioning^ the^sample^or^specimen^carrier^in^a^vertical^or^height^direction^z,^Z,(c) of^positioning^and / or^setting^of^a^focus^or^autofocus^unit^23-2,(d) of^ setting,^ activating,^ and / or^ deactivating^ an^ immersion^ unit^ 21,^ in^ particular^ for^ starting^and / or^stopping^ supply^of^ an^ immersion^ fluid^ to^ the^optical^ engine^ and^ in^particular^ to^ an^imaging^area^in^the^vicinity^of^the^sample^or^specimen^carrier,(e) of^setting,^activating,^and / or^deactivating^one^or^plural^illumination^units^24,(f) of^setting,^activating,^and / or^deactivating^one^or^plural^cameras^units^25,(g) of^setting,^activating,^and / or^deactivating^one^or^plural^filter^selector^and / or^filter^units^26.According^ to^ a^ further^ alternative^or^ additional^preferred^embodiment^of^ the^present^ invention’s^method,^ a^ sample^ or^ specimen^ carrier^ may^ be^ used^ that^ comprises^ one^ or^ plural^ predefined^imaging^targets,^in^particular^fiducial^markers^as^test^and / or^adjusting^samples. One^or^plural^images^of^said^predefined^imaging^targets^or^fiducial^markers^may^be^captured^and^ may^be^analyzed^as^reference^images.Based^ on^ a^ comparison^ result,^ on^ setting^ data,^ and / or^ on^ setting^ command^ optical^ components^and / or^the^first^and / or^second^stages^22,^23-1^may^be^calibrated. The^present^invention^further^relates^to^an^image^acquisition^system,^which^is^configured:- to^ capture^one^or^plural^ images^of^ or^ from^a^ sample^ carrier^ supported^ in^or^on^ a^microscopy^arrangement^and- to^ perform,^ use^ and / or^ to^ be^ used^ in^ a^ method^ according^ to^ the^ present^ invention^ and^ as^described^above.^ The^present^invention’s^image^acquisition^system^may^comprise^a^control^system^that^is^configured^to^ perform^ and / or^ to^ initiate^ an^ image^ acquisition^ method^ according^ to^ an^ embodiment^ of^ the^present^invention. The^control^system^may^comprise^at^least^one^of^an^immersion^control^unit,^a^position^control^unit,^ and^illumination^control^unit,^a^camera^control^unit,^and^a^filter^control^unit.The^ image^acquisition^system^may^comprise^an^optical^engine^ that^may^have^one^or^plural^stage^units^ for^ receiving,^ supporting,^ carrying^ and / or^ controllably^ positioning^ a^ primary^ sample^ or^specimen^carrier.The^ image^ acquisition^ system^may^ also^ comprise^ one^ or^ plural^ image^ analyzer^ units^ which^ are^configured^in^order^to^analyze^said^one^or^plural^captured^images^and / or^to^identify^the^presence^ or^absence^of^an^image^artifact,^in^particular^with^respect^to^the^presence^or^absence^of^at^least^one(i) of^bubbles^of^an^underlying^immersion^fluid,(ii) of^a^misalignment^of^a^sample^carrier^in^the^underlying^microscopy^arrangement,(iii) of^a^misalignment^of^a^sample^or^specimen^on^a^sample^carrier,^and(iv) of^detachment^of^a^sample^or^specimen^or^a^part^thereof^from^a^sample^carrier.These^and^further^details,^advantages^and^features^of^the^present^invention^will^be^described^based^ on^embodiments^of^the^invention^and^by^taking^reference^to^the^accompanying^figures.Figure^1 is^a^schematic^block^diagram^of^an^embodiment^of^the^present^invention’s^image^acquisition^system.Figure^2 is^a^schematic^block^diagram^of^an^embodiment^of^an^optic^unit^to^be^used^in^embodiments^of^the^present^invention’s^image^acquisition^system. In^the^following,^embodiments^and^the^technical^background^of^the^present^invention^are^presented^ in^detail^by^taking^reference^to^accompanying^figures^1^and^2.^Identical^or^equivalent^elements^and^elements^which^ act^ identically^ or^ equivalently^ are^denoted^with^ the^ same^ reference^ signs.^Not^ in^each^case^of^their^occurrence^a^detailed^description^of^the^elements^and^components^is^repeated.The^ depicted^ and^described^ features^ and^ further^properties^ of^ the^ invention’s^ embodiments^ can^arbitrarily^be^isolated^and^recombined^without^leaving^the^gist^of^the^present^invention. In^the^following^and^first^of^all,^a^preliminary^and^very^general^view^is^taken^on^the^enclosed^figure^ 1:Figure^ 1^ demonstrates^ in^ general^ by^means^ of^ a^ schematic^ block^ diagram^ an^ embodiment^ of^ an^image^ acquisition^ system^ 1^ according^ to^ the^ present^ invention,^ which^ is^ configured^ in^ order^ to^perform^or^to^be^used^in^an^image^acquisition^method.According^ to^ an^ embodiment^ of^ the^ present^ invention,^ the^ proposed^ image^ acquisition^method,^comprises,^ in^ particular^ in^ a^ repeating,^ continuous,^ conditional^ closed-loop^ and / or^ conditional^feedback^manner,^processes^of:- capturing^ one^ or^ plural^ images^ of^ or^ from^ a^ sample^ carrier^ supported^ on^ a^ microscopy^arrangement^by^using^an^optical^engine^20,- analyzing^one^or^plural^of^already^captured^images^and^deriving^imaging^status^data^therefrom^by^using^one^or^plural^image^analyzer^units^30,- comparing^said^derived^imaging^status^data^with^predefined^imaging^target^data^and^obtaining^a^comparison^result,- based^on^the^comparison^result,^deriving^setting^data^and / or^a^setting^command,^in^particular^designed^for^setting^the^optical^engine^20,^and- depending^ on^ the^ comparison^ result^ and / or^ based^ on^ the^ setting^ data^ and / or^ the^ setting^command^conditionally^setting^the^optical^engine^20^and / or^its^operation^for^further^images^to^ be^captured. The^process^of^analyzing^said^one^or^plural^captured^images^is^configured^to^identify^the^presence^ or^absence^of^an^image^artifact,^in^particular^with^respect^to^the^presence^or^absence^of^at^least^one^(i) of^bubbles^of^an^underlying^immersion^fluid,(ii) of^a^misalignment^of^a^sample^carrier^in^the^underlying^microscopy^arrangement,(iii) of^a^misalignment^of^a^sample^or^specimen^on^a^sample^carrier,^and(iv) of^detachment^of^a^sample^or^specimen^or^a^part^thereof^from^a^sample^carrier.The^setting^data^and / or^the^setting^command^comprise^at^least^one^(a) of^positioning^or^repositioning^one^or^plural^first^stage^units^22^for^positioning^the^sample^or^specimen^ carrier^ in^ a^ longitudinal^ or^ length^ direction^ x,^ X^ and / or^ a^ transversal^ or^ width^direction^ y,^ Y^ (wherein^ in^ particular^ new / adapted^ X / Y^ stage^ coordinates^ or^ data^representative^therefore^may^be^involved,^in^particular^with^parameters^Stage.X^and^Stage.Y),(b) of^ positioning^ or^ repositioning^ one^ or^ plural^ second^ stage^ units^ 23-1^ for^ positioning^ the^sample^ or^ specimen^ carrier^ in^ a^ vertical^ or^ height^ direction^ z,^ Z^ (wherein^ in^ particular^new / adapted^ Z^ stage^ coordinates^ or^ data^ representative^ therefore^ may^ be^ involved,^ in^particular^with^parameters^Stage.Z),(c) of^positioning^and / or^setting^a^focus^or^autofocus^unit^23-2,(d) of^ setting,^ activating,^ and / or^ deactivating^ an^ immersion^ unit^ 21,^ in^ particular^ for^ starting^and / or^stopping^ supply^of^ an^ immersion^ fluid^ to^ the^optical^ engine^ and^ in^particular^ to^ an^imaging^area^in^the^vicinity^of^the^sample^or^specimen^carrier^(wherein^in^particular^existing^ and / or^ new / adapted^ supply^ amounts^ for^ the^ application^ of^ immersion^ fluids^ may^ be^involved,^in^particular^with^parameters^Im.Residual,^Im.Usage),(e) of^ setting,^ activating,^ and / or^ deactivating^ one^ or^ plural^ illumination^ units^ 24^ (wherein^ in^particular^ new / adapted^ illumination^ channel^ parameters^ are^ involved,^ in^ particular^ with^parameters^Il.CH,^TI,^FLI∼,^Il.CHi.P∼n,^Il.CHi.P∼r),(f) of^ setting,^ activating,^ and / or^ deactivating^ one^ or^ plural^ cameras^ units^ 25^ (wherein^ in^particular^ new / adapted^ camera^ parameters^ are^ involved,^ in^ particular^ with^ parameters^CAM(i),^ROI,^#^of^Fr.,^Frame),(g) of^setting,^activating,^and / or^deactivating^one^or^plural^ filter^selector^and / or^ filter^units^26^(wherein^ in^ particular^ new / adapted^ filter^ parameters^ are^ involved,^ in^ particular^ with^parameters^Filter.CH).According^ to^ a^ preferred^ embodiment^ of^ the^ present^ invention’s^method,^ a^ sample^ or^ specimen^carrier^may^be^used^that^comprises^one^or^plural^predefined^imaging^targets,^in^particular^fiducial^ markers^as^test^and / or^adjusting^samples. One^or^plural^images^of^said^predefined^imaging^targets^or^fiducial^markers^may^be^captured^and^ may^be^analyzed^as^reference^images.Based^ on^ a^ comparison^ result,^ on^ setting^ data,^ and / or^ on^ setting^ command^ optical^ components^and / or^the^first^and / or^second^stages^22,^23-1^may^be^calibrated.According^ to^ the^ present^ invention,^ also^ an^ image^ acquisition^ system^ 1^ is^ proposed,^ which^ is^configured^to:- to^ capture^one^or^plural^ images^of^ or^ from^a^ sample^ carrier^ supported^ in^or^on^ a^microscopy^arrangement^and- to^ perform,^ use^ and / or^ to^ be^ used^ in^ a^ method^ according^ to^ the^ present^ invention^ and^ as^described^above.^The^ present^ invention’s^ image^ acquisition^ system^ 1^ may^ comprises^ a^ control^ system^ 10^ that^ is^configured^to^perform^and / or^to^initiate^an^image^acquisition^method^according^to^an^embodiment^ of^the^present^invention.The^ control^ system^ 10^ may^ comprise^ at^ least^ one^ of^ an^ immersion^ control^ unit^ 11,^ a^ position^control^unit^12,^13,^and^illumination^control^unit^14,^a^camera^control^unit^15,^and^a^filter^control^ unit^16.The^ image^ acquisition^ system^1^may^ comprise^ an^ optical^ engine^20^ that^may^have^one^ or^plural^stage^units^22,^23-1^ for^receiving,^supporting,^carrying^and / or^controllably^positioning^a^primary^sample^or^specimen^carrier. The^image^acquisition^system^1^may^also^comprise^one^or^plural^image^analyzer^units^30^which^are^ configured^in^order^to^analyze^said^one^or^plural^captured^images^and / or^to^identify^the^presence^ or^absence^of^an^image^artifact,^in^particular^with^respect^to^the^presence^or^absence^of^at^least^one(i) of^bubbles^of^an^underlying^immersion^fluid,(ii) of^a^misalignment^of^a^sample^carrier^in^the^underlying^microscopy^arrangement,(iii) of^a^misalignment^of^a^sample^or^specimen^on^a^sample^carrier,^and(iv) of^a^detachment^of^a^sample^or^specimen^or^a^part^thereof^from^a^sample^carrier.As^ shown^ in^ figure^ 1,^ too,^ the^ optical^ engine^ 20^ comprises^ an^ optic^ unit^ 27^ to^ be^ used^ in^embodiments^ of^ the^ present^ invention’s^ image^ acquisition^ system^ 1^ and^ to^ be^ controlled^ by^ an^underlying^optic^control^17^comprises^in^the^control^system^10^via^. These^and^further^aspects^of^the^present^invention^will^also^be^described^in^detail^in^the^following^ passages: The^present^invention^inter^alia^relates^to^robust^microscopy^image^acquisition,^in^particular^with^ control^feed^backs. Automated^slide^scan^routines^are^herewith^implemented^on^microscope^environments,^which^are^ in^particular^configured^and^designed^to^overcome^the^commonly^limited^handling^of^one^or^plural^ of^(i)^insertion^misalignment^in^lateral^and^axial^dimensions,^(ii)^deformation^of^slides,^(iii)^tissue^ detachment,^(iv)^immersion^liquid^artifacts,^and^(v)^imaging^throughput.Inter^alia^control^ feedback^designs^are^proposed^which^are^based^on^acquired^ images^ in^order^ to^reduce^ misalignment^ errors,^ sample^ and / or^ slide’s^ artifacts^ and / or^ to^ optimize^ imaging^throughput. The^block^diagram^of^figure^1^illustrates^an^embodiment^of^the^present^invention’s^potential^closed^ control^loop^for^an^image^acquisition^system^1,^in^particular^for^microscopy^applications. An^embodiment^of^such^a^system^1^may^be^thought^of^as^combination^of^three^major^subsystems:^ (a)^a^control^system^10,^(b)^an^optical^engine^20,^and^(c)^an^image^analyzer^30. The^desired^images^to^be^obtained^from^a^microscope^slide^as^a^primary^sample^and / or^specimen^ carrier^may^be^defined,^acquired,^and^fed^into^the^control^system^10,^in^particular^via^processing^G.The^control^system^10^may^have^multiple^sub-controllers^11^ to^16^ that^are^configured^to^control^subassemblies^21^to^26^within^the^optical^engine^20:^e.g.^a^position^X / Y^controller^12^may^control^a^ stage^X / Y^subassembly^22^within^the^optical^engine^20.^ The^control^system^10^may^send^commands^-^in^particular^via^a^respective^process,^processing^or^ procedure^A^to^F^and / or^O^-^to^the^optical^engine^20^in^order^- to^position^a^slide^or^any^involved^primary^sample^carrier^or^specimen^carrier^in^the^X,^Y^and^Z^directions^or^coordinates^and / or^to^obtain^measurements^of^coordinates,- to^apply^an^immersion^fluid,- to^turn^on^a^certain^combination^of^wavelengths^in^an^underlying^illumination^and / or^excitation^source,-^ to^change^a^filter^location^and / or^a^channel,^and / or^to^snap^images,^and / or- to^ control,^ drive,^ operate,^ adjust,^monitor^ and / or^ acquire^ date^ from^ the^ optic^ unit^ 27^ and^ its^components^27-1,^27-2,^…,^in^particular^via^operation^and^action^of^the^optic^control^17^and^the^ processing^O. Data^generated^by^the^optical^engine^20^may^be^send^to^and / or^processed^by^the^image^analyzer^30.The^ image^ data^ are^ processed^ in^ order^ to^ identify^ artifacts^ introduced,^ e.g.^ immersion^ bubbles,^misalignment^in^X,^Y^or^Z,^etc.^along^with^other^information^collected^from^the^optical^engine^20,^the^ image^analyzer^30^may^instruct^a^data^transfer^and^storage^module^or^unit^40^to^transfer^and^store^ certain^information. In^addition,^the^image^analyzer^30^may^-^in^particular^via^processing^I^-^provide^processed^image^quality^ results,^ e.g.^ immersion^ bubble^ error,^ misalignment,^ etc.^ to^ the^ control^ system^ 10^ -^ in^particular^via^processing^J^-^in^order^to^incorporate^into^the^logic^calculation^for^the^commands^to^ be^sent^to^the^optical^engine. In^the^following,^a^few^examples^of^how^an^image^acquisition^system^1^with^a^closed^control^loop^ can^be^used^in^order^to^generate^high^quality^and^high^reliability^data^or^image^data.1.^ Image^quality^analysis^and^control^may^be^performed^ in^order^ to^ reduce^at^ least^one^of^ image^acquisition^errors,^e.g.^immersion^bubbles,^a^misalignment^or^the^like.Artifacts^ from^ immersion^ fluids,^ e.g.^ bubbles^ between^ the^ objective^ lens^ and^ the^ sample^ under^observation,^may^impact^the^contrast^and / or^cast^shadow^onto^the^images^acquired.^By^employing^ computer^vision^analysis^in^the^image^analyzer^subsystem,^such^artifacts^can^be^identified^and / or^ reduced.^A^feedback^signal^on^this^error^type^may^be^provided^to^the^control^system.^The^control^ system^10^may^perform^various^tasks,^e.g.^to^go^to^a^same^x / y / z^location^and / or^to^reimage,^to^flush^ the^immersion^liquid^and^ / or^retake^the^image,^etc.2.^Slide^ insertion^misalignment^correction^may^be^performed^by^using^reference^ images^ in^bright^field^or^fluorescence^modality,^e.g.^DAPI.Slide^ insertion^ misalignment^ is^ a^ typical^ error^ source^ due^ to^ the^ mechanical^ tolerance^ of^ slide^assembly^and^is^much^larger^than^what^is^required^for^optical^imaging. A^measure^and^correct^routine^can^be^implemented^in^the^invention’s^image^acquisition^system. An^example^routine^may^be^or^comprise^a^processing^sequence^as^follows:(a) The^control^system^10^may^send^and / or^position^a^slide^or^primary^sample^or^specimen^carrier^to^a^few^locations^with^known^targets^on^the^slide.(b) The^ optical^ engine^ 20^may^ take^ images^ of^ the^ known^ targets^ at^ said^ locations.^ The^ known^targets^can^be^fiducials^embedded^into^the^slides^or^carriers^or^formed^on^the^slide^or^carrier^ surface,^e.g.^cell^nucleus^stained^by^DAPI.(c) The^ image^ analyzer^ 30^ may^ process^ acquired^ images^ and / or^ calculate^ an^ amount^ of^misalignment^ of^ the^ known^ targets^ within^ the^ acquired^ images.^ The^ derived^ amount^ of^misalignment^may^be^sent^to^the^control^system^10.(d) The^ control^ system^ 10^ may^ adopt^ the^ measured^ misalignments^ in^ order^ to^ calibrate^ an^underlying^stage^coordinate,^e.g.^by^using^the^misalignments^as^a^measure^of^offset.(e) Steps^(a),^ (b),^ (c)^as^described^above^may^be^ repeated^until^ the^amount^of^misalignment^ fall^within^target^specifications. 3.^Tissue^detachment^detection^and^warning^may^be^performed^by^using^image^contrast^calculation.Tissue^detachment^ from^slide^or^ carrier^ surface^ is^ an^ issue^ for^microscopy^ imaging.^Detachment^occurs^ either^ at^ the^ start^ of^ imaging^ (e.g.^ in^ case^ that^ a^ local^ region^ of^ a^ tissue^ sample^ is^ not^ in^contact^with^the^slide^or^carrier^surface)^or^during^the^multiple^reagent^treatment^steps^in^between^ the^imaging^steps.Tissue^ detachment^ results^ in^ local^ region^ or^ whole^ tissue^ move^ away^ from^ the^ slide^ or^ carrier^surface. The^image^analyzer^30^may^identify^a^local^or^a^complete / whole^tissue^region^detachment^by^the^ contact^of^the^images^in^those^regions. The^image^analyzer^30^may^send^such^information^to^the^control^system^10.The^ control^ system^10^may^perform^various^processes,^ including^ a^ retake^of^ images^ at^ the^ same^location^to^confirm^an^alleged^detachment,^to^move^to^a^nearby^region^to^take^images^for^the^image^ analyzer^to^measure^a^detachment^in^a^nearby^region,^etc. Many^more^other^examples^can^be^developed^on^this^closed^feedback^loop^image^acquisition^system^ 1. In^addition^to^improve^the^reliability^as^illustrated^in^examples^above,^the^system^1^can^also^be^used^to^speed^up^the^image^data^acquisition.^ ^For^example,^register^region^with^detached^tissue^to^skip^those^regions.As^already^mentioned^above,^figure^2 demonstrates^ by^ means^ of^ a^ schematic^ block^ diagram^ an^embodiment^provision^of^an^optic^unit^27^comprised^in^an^embodiment^of^the^optical^engine^20^to^ be^used^in^embodiments^of^the^present^invention’s^image^acquisition^system^1^and^to^be^controlled^ by^an^underlying^optic^control^17^comprised^in^an^embodiment^of^the^control^system^10^and^via^a^ processing^O. The^optic^unit^may^comprise^(a)^one^or^plural^objective^lenses^27-1,^one^or^plural^tube^lenses^27-4,^one^ or^ plural^ mirrors^ 27-5^ and / or^ one^ or^ plural^ various^ other^ active^ and / or^ passive^ optical^components^27-6.Particular^ items^ of^ the^ objective^ lens^ 27-1^may^ actively^ and / or^manually^ be^ controlled,^ e.g.^ the^position^of^a^correction^collar^27-2^and / or^a^temperature^adjusting^means^27-3,^in^particular^of^an^underlying^ case^which^ comprises,^ supports,^ surround^ and / or^makes^ up^ a^ compound^ lens^ of^ the^objective^lenses^27-1. Active^and / or^manual^control^may^also^apply^to^any^other^component^of^the^optic^unit^27.Summing^ up^ all^ the^ circumstances^ as^ given^ above,^ present^ invention^ -^ in^ general^ but^ not^ only^ -^refers^ to^ an^ image^ acquisition^ method,^ comprising,^ in^ particular^ in^ a^ repeating,^ continuously^performed,^ conditional^ closed-loop^ and / or^ conditional^ feedback^manner,^ processes^ of^ capturing^one^or^plural^images^of^or^from^a^sample^carrier^supported^on^a^microscopy^arrangement^by^using^an^ optical^ engine^ 20,^ analyzing^ one^ or^ plural^ of^ already^ captured^ images^ and^ deriving^ imaging^status^ data^ therefrom^ by^ using^ one^ or^ plural^ image^ analyzer^ units^ 30,^ comparing^ said^ derived^imaging^status^data^with^predefined^imaging^target^data^and^obtaining^a^comparison^result,^based^ on^the^comparison^result,^deriving^setting^data^and / or^a^setting^command,^in^particular^designed^for^ setting^ the^ optical^ engine^ 20,^ and^ depending^ on^ the^ comparison^ result^ and / or^ based^ on^ the^setting^ data^ and / or^ the^ setting^ command^ conditionally^ setting^ the^ optical^ engine^ 20^ and / or^ its^operation^ for^ further^ images^ to^ be^ captured.^ Also,^ an^ image^ acquisition^ system^ 1^ is^ suggested,^which^is^configured^to^capture^one^or^plural^images^of^or^from^a^sample^carrier^supported^in^or^on^a^ microscopy^arrangement^and^to^perform,^to^use^and / or^to^be^used^in^the^image^acquisition^method.

[0002] List^of^Reference^Signs1 image^acquisition^system10 control^system11 immersion^control^unit12 position / positioning^control^unit^for^X^and^Y^directions13 position / positioning^control^unit^for^Z^direction14 illumination^control^unit15 camera^control^unit16 filter^control^unit17 optic^control^unit20 optical^engine21 immersion^unit22 stage^for^positioning^in^X^and^Y^directions23-1 stage^for^positioning^in^Z^direction23-2 auto^focus / autofocus^unit24 illumination^unit(s)25 camera^unit(s)26 filter^selector^unit(s)^ / ^filter^unit(s)27 (primary)^optic^unit27-1 objective^lens27-2 correction^collar27-3 temperature^adjusting^means27-4 tube^lens27-5 mirror27-6 passive / active^optical^component30 image^analyzer^unit40 data^transfer^unit / data^storage^unit50 supply^of^(desired)^images^from^sample / specimen^carrierA supply^ of^ setting / control^ data^ to^ the^ immersion^ unit^ 21^ (in^ particular^ for^supplying / discharging^immersion^fluid / liquid)B supply^of^setting / control^data^to^X / Y^stage^22^(in^particular^for^new / adapted^X / Y^position^data)C supply^ of^ setting / control^ data^ to^ X / Y^ stage^ 23-1^ and / or^ 2^ or^ autofocus^ unit^ 23-2^ (in^ particular^for^new / adapted^Z^position^data)D supply^ of^ setting / control^ data^ to^ one^ or^ plural^ illumination^ units^ 24^ (in^ particular^ with^respect^ to^an^ illumination^channel,^an^ illumination^ intensity,^an^ illumination^spectrum,^an^illumination^direction)E supply^of^setting / control^data^to^one^or^plural^camera^units^25^(in^particular^with^respect^to^image^setting^data,^imaging^region,^resolution,^repetition^rate)F supply^of^setting / control^data^to^one^or^plural^filter^units^26^(in^particular^with^respect^to^filter^attenuation,^filter^spectrum)^G supply^of^data^of^captured^images^and / or^of^setting / control^data^to^the^control^system^10H supply^ of^ image^ data^ of^ captured^ images^ and / or^ of^ setting / control^ data^ to^ one^ or^ plural^image^analyzer^units^30I supply^of^analysis^and / or^setting / control^data^ to^one^or^plural^data^ transfer / data^storage^units^40J supply^of^analysis^and / or^setting / control^data^to^the^control^system^10O supply^of^setting / control^data^to^one^or^plural^components^of^the^optic^unit^27x spatial^directionX direction^of^the^longitudinal / length^extensiony spatial^directionY direction^of^the^transversal / width^extensionz spatial^directionZ direction^of^the^height^extension

Claims

Claims1. Image^acquisition^method,^comprising,^in^particular^in^a^repeating,^continuous,^conditional^closed-loop^and / or^conditional^feedback^manner,^processes^of: -capturing^one^or^plural^images^of^or^from^a^sample^carrier^supported^on^a^microscopy^arrangement^by^using^an^optical^engine^(20), -analyzing^ one^ or^ plural^ of^ already^ captured^ images^ and^ deriving^ imaging^ status^ data^therefrom^by^using^one^or^plural^image^analyzer^units^(30), -comparing^ said^ derived^ imaging^ status^ data^ with^ predefined^ imaging^ target^ data^ and^obtaining^a^comparison^result, -based^ on^ the^ comparison^ result,^ deriving^ setting^ data^ and / or^ a^ setting^ command,^ in^particular^designed^for^setting^the^optical^engine^(20),^and -depending^on^the^comparison^result^and / or^based^on^the^setting^data^and / or^the^setting^command^conditionally^setting^the^optical^engine^(20)^and / or^ its^operation^ for^ further^images^to^be^captured.

2. Image^acquisition^method^according^to^claim^1,^wherein^the^process^of^analyzing^said^one^or^ plural^ captured^ images^ is^ configured^ to^ identify^ the^ presence^ or^ absence^ of^ an^ image^artifact,^in^particular^with^respect^to^the^presence^or^absence^of^at^least^one^ (i) of^bubbles^of^an^underlying^immersion^fluid,(ii) of^a^misalignment^of^a^sample^carrier^in^the^underlying^microscopy^arrangement,(iii) of^a^misalignment^of^a^sample^or^specimen^on^a^sample^carrier,^and(iv) of^detachment^of^a^sample^or^specimen^or^a^part^thereof^from^a^sample^carrier.

3. Image^acquisition^method^according^to^any^one^of^the^preceding^claims,^wherein^the^setting^data^and / or^the^setting^command^comprise^at^least^one^ (a) of^positioning^or^repositioning^of^one^or^plural^first^stage^units^(22)^for^positioning^the^sample^ or^ specimen^ carrier^ in^ a^ longitudinal^ or^ length^ direction^ (x,^ X)^ and / or^ a^transversal^or^width^direction^(y,^Y), (b) of^ positioning^ or^ repositioning^ of^ one^ or^ plural^ second^ stage^ units^ (23-1)^ for^positioning^the^sample^or^specimen^carrier^in^a^vertical^or^height^direction^(z,^Z), (c) of^positioning^and / or^setting^of^a^focus^or^autofocus^unit^(23-2),(d) of^ setting,^ activating,^ and / or^ deactivating^ an^ immersion^ unit^ (21),^ in^ particular^ for^starting^ and / or^ stopping^ supply^ of^ an^ immersion^ fluid^ to^ the^ optical^ engine^ and^ in^particular^to^an^imaging^area^in^the^vicinity^of^the^sample^or^specimen^carrier,(e) of^setting,^activating,^and / or^deactivating^one^or^plural^illumination^units^(24),(f) of^setting,^activating,^and / or^deactivating^one^or^plural^cameras^units^(25),(g) of^setting,^activating,^and / or^deactivating^one^or^plural^filter^selector^and / or^filter^units^(26).

4. Image^acquisition^method^according^to^any^one^of^the^preceding^claims,^wherein:- a^sample^or^specimen^carrier^ is^used^ that^comprises^one^or^plural^predefined^ imaging^targets,^in^particular^fiducial^markers^as^test^and / or^adjusting^samples,^and -one^or^plural^images^of^said^predefined^imaging^targets^or^fiducial^markers^are^captured^and^are^analyzed^as^reference^images.

5. Image^acquisition^method^according^to^any^one^of^the^preceding^claims,^wherein^based^on^the^ comparison^ result,^ the^ setting^data,^ and / or^ the^ setting^ command^optical^ components^and / or^the^first^and / or^second^stages^(22,^23-1)^are^calibrated.

6. Image^acquisition^system^(1),^which^is^configured^to:- capture^one^or^plural^images^of^or^from^a^sample^carrier^supported^in^or^on^a^microscopy^arrangement^and -perform,^use^and / or^to^be^used^in^a^method^according^to^any^one^of^the^preceding^claims.^7. Image^acquisition^system^(1)^according^to^claim^6,^which^comprises^a^control^system^(10)^that^is^configured^to^perform^and / or^to^initiate^a^method^according^to^any^one^of^claims^1^to^ 5.

8. Image^ acquisition^ system^ (1)^ according^ to^ claim^ 6,^ wherein^ the^ control^ system^ (10)^comprises^at^ least^one^of^an^ immersion^control^unit^(11),^a^position^control^unit^(12,^13),^and^illumination^control^unit^(14),^a^camera^control^unit^(15),^and^a^filter^control^unit^(16).

9. Image^acquisition^system^(1)^according^ to^any^one^of^claims^6^ to^8,^comprising^an^optical^engine^ (20)^ comprising^ one^ or^ plural^ stage^ units^ (22,^ 23-1)^ for^ receiving,^ supporting,^carrying^and / or^controllably^positioning^a^primary^sample^or^specimen^carrier.

10. Image^acquisition^system^(1)^according^to^any^one^of^claims^6^to^8,^comprising^one^or^plural^image^ analyzer^ units^ (30)^ which^ are^ configured^ in^ order^ to^ analyze^ said^ one^ or^ plural^captured^ images^ and / or^ to^ identify^ the^ presence^ or^ absence^ of^ an^ image^ artifact,^ in^particular^with^respect^to^the^presence^or^absence^of^at^least^one^(i) of^bubbles^of^an^underlying^immersion^fluid,(ii) of^a^misalignment^of^a^sample^carrier^in^the^underlying^microscopy^arrangement,(iii) of^a^misalignment^of^a^sample^or^specimen^on^a^sample^carrier,^and(iv) of^detachment^of^a^sample^or^specimen^or^a^part^thereof^from^a^sample^carrier.

Images