Gel microdrops in genetic analysis

Abstract

The invention provides methods of nucleic acid analysis. Such methods entail forming a population of gel microdrops encapsulating a population of biological entities, each entity comprising a nucleic acid, whereby at least some microdrops in the population each encapsulate a single entity. The population of gel microdrops is then contacted with a probe under conditions whereby the probe specifically hybridizes to at least one complementary sequence in the nucleic acid in at least one gel microdrop. At least one gel microdrop is then analyzed or detected. The biological entities can be cells, viruses, nuclei and chromosomes.

1 - 35 . (canceled) 
     
     
         36 . A method of clinical analysis comprising:
 encapsulating biological entities in gel microdrops, wherein said biological entities are from a tissue sample from a patient;   storing the microdrops for at least an hour; and   performing a clinical analysis on said encapsulated biological entities.   
     
     
         37 . The method of  claim 36 , wherein the microdrops are stored for at least six months. 
     
     
         38 . The method of  claim 36 , wherein the clinical analysis is performed on chromosomes from the microdrops. 
     
     
         39 . The method of  claim 36 , wherein the clinical analysis comprises
 contacting the microdrops with a probe that is complementary to a nucleic acid molecule, the presence of which is indicative of a disease state and;   diagnosing the existence or prognosis of the disease from the hybridization or lack of hybridization of the probe to a nucleic acid molecule within an encapsulated cell.   
     
     
         40 . The method of  claim 39 , wherein the disease is a disease associated with a genetic defect. 
     
     
         41 . The method of  claim 39 , wherein the disease is cancer. 
     
     
         42 . The method of  claim 39 , wherein the probe is complementary to at an exonic segment of a gene. 
     
     
         43 . The method of  claim 39 , wherein the probe is complementary to at least two successive exons of a gene and specifically hybridizes to RNA expressed from the gene. 
     
     
         44 . The method of  claim 39 , wherein the disease comprises the presence of a virus. 
     
     
         45 . The method of  claim 39 , wherein the virus is a retrovirus. 
     
     
         46 . A method of storing a biological entity in a gel microdrop, comprising: forming a population of gel microdrops encapsulating a population of biological entities within a gel matrix; and storing at least a portion of the population of gel microdrops under conditions to preserve the biological entities intact. 
     
     
         47 . The method of  claim 46 , wherein the biological entities comprise cells, viruses, organelles, mitochondria, chloroplasts, nuclei, chromosomes, proteins, nucleic acids, or fragments thereof. 
     
     
         48 . The method of  claim 46 , wherein the population of gel microdrops is stored for at least one hour, for at least one day, for at least one week, for at least one month, for at least six months, for at least one year, for at least two years, or for at least five years. 
     
     
         49 . The method of  claim 46 , wherein the gel microdrop comprises agarose. 
     
     
         50 . The method of  claim 46 , wherein at least a portion of the population of gel microdrops encapsulate a single biological entity. 
     
     
         51 . The method of  claim 50 , wherein the biological entity comprises a nucleic acid hybridized to a probe comprising a complementary sequence prior to storage. 
     
     
         52 . The method of  claim 46 , further comprising releasing the gel microdrop encapsulated biological entity by digesting the gel matrix. 
     
     
         53 . A method of storing a patient sample in a gel microdrop, comprising: obtaining a biological sample from a patient; forming a population of gel microdrops encapsulating the biological sample within a gel matrix; and storing at least a portion of the population of gel microdrops under conditions to preserve the patient sample intact and without degradation. 
     
     
         54 . The method of  claim 53 , wherein the biological sample from the patient comprises one or more cells taken from a tissue or blood sample. 
     
     
         55 . The method of  claim 54 , wherein the one or more cells are propagated prior to encapsulation within the population of gel microdrops. 
     
     
         56 . The method of  claim 54 , wherein the tissue sample is obtained from a location within the patient suspected of comprising a genetic abnormality or an indicia of suspected disease. 
     
     
         57 . The method of  claim 56 , wherein the suspected disease is a cancer, an autoimmune disease, or a disease of the central nervous system. 
     
     
         58 . The method of  claim 53 , wherein the population of gel microdrops is stored for at least one hour, for at least one day, for at least one week, for at least one month, for at least six months, for at least one year, for at least two years, or for at least five years. 
     
     
         59 . The method of  claim 53 , wherein at least a portion of the population of gel microdrops encapsulate a single biological entity from the sample, the biological entity comprising a cell, a chromosome, or a nucleic acid. 
     
     
         60 . The method of  claim 53 , further comprising releasing the gel microdrop encapsulated biological sample by digesting the gel matrix.