Efficient algorithm for PCR testing of blood samples

Abstract

Systems, processes, and devices are provided which are useful for testing blood or plasma donations to detect those specific donations which are contaminated by a virus above a predetermined level. An apparatus and process is described which forms individual, separately sealed and connected sample containers from a flexible hollow tubing segment connected to a fluid donation container. The tubing segment is sealed at spaced-apart intervals along its length, with tubing segment portions in the intervals between the seals defining containers, each of which holds a portion of a plasma sample. The contents of the containers are formed into pools which are subsequently tested for virus contamination by a high-sensitivity test such as PCR. The pools are tested in accordance with an algorithm by which a sample from each donation is mapped to each element of an N-dimensional matrix or grid. Each element of the matrix is identified by a matrix identifier, X rcs , where rcs defines the dimensional index. An aliquot is taken from each sample, and subpools are formed, each subpool comprising aliquots of samples in which one dimensional index is fixed. All of the subpools are tested in one PCR test cycle. The dimensional indicia of each positive subpool is evaluated mathematically in accordance with a reduction by the method of minors, thereby unambiguously identifying a unique element in the grid, thereby unambiguously identifying a uniquely positive blood or plasma donation.

What is claimed is:  
     
         1 . A method for forming subpools for use in testing for presence of a specified agent in a set of fluid samples, the method comprising the operations of: 
 (a) associating each of the fluid samples with a distinct matrix element of an N-dimensional matrix, each of the matrix elements being identified by values of N indices, the N indices corresponding one-to-one to the N dimensions of the matrix;    (b) forming N aliquots from each of the fluid samples; and    (c) combining aliquots to form the subpools such that each of the subpools comprises one aliquot from each of the fluid samples associated with matrix elements that have an identical value for one of the N indices.    
     
     
         2 . The method of  claim 1 , further comprising the operations of: 
 (d) testing each of the subpools to detect presence of the specified agent; and    (e) producing a positive indication for one of the subpools when the presence of the specified agent is detected in said subpool.    
     
     
         3 . The method of  claim 2 , further comprising the operations of: 
 (f) combining identities of all subpools that have a positive indication to identify at least one corresponding positively indicated fluid sample.    
     
     
         4 . The method of  claim 1 , wherein the N indices have an identical range of values.  
     
     
         5 . The method of  claim 1 , wherein N is equal to 3.  
     
     
         6 . The method of  claim 2 , wherein operation (d) is a high-sensitivity test.  
     
     
         7 . The method of  claim 6 , wherein the high-sensitivity test is a polymerase chain reaction (PCR) test.  
     
     
         8 . The method of  claim 3 , wherein N is equal to 3 and there are 3 sets of said subpools corresponding to the 3 indices, each subpool of the 3 sets of subpools being identified by a specific value of a corresponding one of the N indices.  
     
     
         9 . The method of  claim 8 , wherein operation (f) results in identifying K positively indicated fluid samples, K being an integer greater or equal to 1, when one of the N sets of subpools has K subpools having positive indication and each of the remaining N-1 sets of subpools has only one subpool having positive indication.  
     
     
         10 . The method of  claim 8 , wherein operation (f) results in identifying a set of candidates for positively indicated fluid samples when more than one of the N sets of subpools has more than one subpool having positive indication.  
     
     
         11 . The method of  claim 10 , further comprising the operation of: 
 forming a new aliquot from each of the candidates for positively indicated fluid samples;    testing each of the new aliquots to detect presence of the specified agent; and    producing a positive indication for one of the new aliquots when presence of the specified agent is detected in said new aliquot, said new aliquot identifying a corresponding positively indicated fluid sample.