Manipulating and detecting biological samples

Abstract

Disclosed herein, inter alia, are compositions and methods for efficient transfer and analyses of cellular material, tissue samples, such as tissue sections, using carrier substrates.

What is claimed is: 
     
         1 - 64 . (canceled) 
     
     
         65 . A method of obtaining an image of a portion of a tissue section, said method comprising:
 A) immobilizing the tissue section onto a hydrogel carrier substrate to generate a sample-carrier construct comprising the carrier substrate and the tissue section;   B) removing a portion of the sample-carrier construct, wherein the portion comprises a portion of the carrier substrate and a portion of the tissue section;   C) contacting the tissue section of the portion of the sample-carrier construct with a receiving substrate to generate an immobilized tissue section;   D) removing the hydrogel carrier substrate from the immobilized tissue section; and   E) imaging the tissue section, thereby obtaining an image of a portion of the tissue section.   
     
     
         66 . The method of  claim 65 , wherein prior to step E), the method further comprises permeabilizing the immobilized tissue section. 
     
     
         67 . The method of  claim 65 , wherein prior to step E), the method does not comprise permeabilizing the immobilized tissue section. 
     
     
         68 . The method of  claim 65 , wherein step E) comprises phase-contrast microscopy, bright-field microscopy, Nomarski differential-interference-contrast microscopy, dark field microscopy, electron microscopy, or cryo-electron microscopy. 
     
     
         69 . The method of  claim 65 , wherein prior to step E), the method further comprises contacting the immobilized tissue section with one or more imaging reagents or stains. 
     
     
         70 . The method of  claim 69 , wherein the one or more imaging reagents or stains comprise hematoxylin and eosin (H&E) staining reagents. 
     
     
         71 . The method of  claim 69 , wherein the one or more imaging reagents or stains comprise phase-contrast microscopy, bright-field microscopy, Nomarski differential-interference-contrast microscopy, or dark field microscopy imaging reagents. 
     
     
         72 . The method of  claim 69 , wherein the one or more imaging reagents or stains comprise electron microscopy or cryo-electron microscopy imaging reagents. 
     
     
         73 . The method of  claim 65 , wherein the thickness of the tissue section is about 1 µm to about 20 µm. 
     
     
         74 - 75 . (canceled) 
     
     
         76 . The method of  65 , wherein the tissue section is embedded in an embedding material comprising paraffin wax, polyepoxide polymer, polyacrylic polymer, agar, gelatin, celloidin, cryogel, optimal cutting temperature (OCT) compositions, glycols, or a combination thereof. 
     
     
         77 . The method of  claim 76 , further comprising removing the embedding material. 
     
     
         78 . The method of  claim 76 , further comprising removing the embedding material prior to step C). 
     
     
         79 . The method of  claim 65 , wherein the hydrogel carrier substrate comprises agarose, amylose, amylopectin, alginate, gelatin, cellulose, polyolefin, polyethylene glycol, polyvinyl alcohol, and/or acrylate polymers and copolymers thereof. 
     
     
         80 . The method of  claim 65 , wherein the hydrogel carrier substrate comprises agarose, amylose, or amylopectin. 
     
     
         81 . The method of  claim 65 , wherein the hydrogel carrier substrate comprises less than about 5% agarose. 
     
     
         82 . The method of  claim 65 , wherein the hydrogel carrier substrate further comprises a support scaffold. 
     
     
         83 . The method of  claim 82 , wherein the support scaffold comprises a thermoplastic elastomer. 
     
     
         84 . (canceled) 
     
     
         85 . The method of  claim 65 , wherein the hydrogel carrier substrate comprises a Young’s modulus of about 5 kPa to about 30 kPa. 
     
     
         86 . The method of  claim 65 , wherein the sample-carrier construct comprises interfacial water, wherein the interfacial water is between the carrier substrate and the tissue section. 
     
     
         87 . The method of  claim 65 , wherein the hydrogel carrier substrate comprises about 80% to about 99% water. 
     
     
         88 . The method of  claim 65 , wherein the receiving substrate comprises a functionalized glass surface or a functionalized plastic surface. 
     
     
         89 . The method of  claim 88 , wherein the functionalized glass surface comprises (3-aminopropyl)triethoxysilane (APTES), (3-Aminopropyl)trimethoxysilane (APTMS), γ-Aminopropylsilatrane (APS), N-(6-aminohexyl)aminomethyltriethoxysilane (AHAMTES), polyethylenimine (PEI), 5,6-epoxyhexyltriethoxysilane, or triethoxysilylbutyraldehyde, or a combination thereof. 
     
     
         90 . The method of  claim 65 , wherein prior to step C), the sample-carrier construct is stored for one or more days. 
     
     
         91 - 92 . (canceled) 
     
     
         93 . The method of  claim 90 , wherein the sample-carrier construct is stored at less than about 25° C. 
     
     
         94 - 95 . (canceled) 
     
     
         96 . The method of  claim 65 , wherein step D) comprises physically removing, thermally removing, chemically removing, or enzymatically removing. 
     
     
         97 - 98 . (canceled) 
     
     
         99 . The method of  claim 65 , wherein the sample-carrier construct comprises substantially uniform adhesion between the tissue section and the carrier substrate. 
     
     
         100 . The method of  claim 65 , wherein the tissue section is immobilized onto the surface of the hydrogel carrier substrate. 
     
     
         101 . The method of  claim 65 , wherein substantially all of the tissue section of the portion is immobilized to the receiving substrate. 
     
     
         102 . The method of  claim 65 , wherein prior to step A), the hydrogel carrier substrate is solid or semi-solid. 
     
     
         103 . A method of immobilizing a portion of a tissue section to a receiving substrate, wherein the tissue section comprises a thickness of about 1 µm to about 50 µm, said method comprising: contacting the tissue section with a hydrogel carrier substrate to generate a sample-carrier construct comprising the carrier substrate and the tissue section; removing a portion of the sample-carrier construct, wherein the portion comprises a portion of the carrier substrate and a portion of the tissue section; contacting the tissue section of the portion of the sample-carrier construct with the receiving substrate thereby immobilizing the tissue section to the receiving substrate.