Biochips and related automated analyzers and methods

Abstract

The present invention provides biochips that include: (a) a plurality of cards, each card having a plurality of card apertures extending therethrough, each respective card aperture having one or more cross sectional areas; and (b) a plurality of gaskets, at least one gasket residing intermediate two neighboring cards, each gasket having a plurality of gasket apertures extending therethrough. At least some of the gasket apertures have an area that is greater than that of at least one adjacent card aperture. Different sets of the gasket apertures and card apertures define a plurality of fluidic flow channels. Also provided herein are methods of making and using biochips.

That which is claimed: 
     
         1 . A biochip subassembly comprising:
 a flexible gasket having an array of substantially box shaped gasket apertures; and   a substantially rigid card affixed to the flexible gasket, the card having a bioactive material and having an array of substantially rectangular shaped card apertures with a width dimension being less than a width dimension of the gasket apertures, wherein the gasket resides over the card such that a respective gasket aperture resides over a corresponding card aperture with the card aperture residing proximate a side edge of the gasket aperture and wherein a surface of the card under the gasket aperture is exposed through the gasket aperture and accessible to contact with a fluid sample.   
     
     
         2 . A biochip comprising a plurality of the biochip subassemblies of  claim 1  in a stacked relationship and arranged so that adjacent first and second biochip subassemblies are configured with the first biochip subassembly having first card apertures positioned proximate a left side of first gasket apertures and the second biochip subassembly having second card apertures positioned proximate a right side of second gasket apertures. 
     
     
         3 . A biochip, comprising:
 a plurality of stackable card/gasket members, each member having an opposing upper and lower surface and a plurality of apertures extending therethrough, the stackable members being aligned so that the apertures define fluidic flow channels, wherein the channels have alternating substantially horizontal and substantially vertical surfaces, with at least some of the substantially horizontal surfaces defining at least one analytical site.   
     
     
         4 . The biochip of  claim 3 , wherein a surface of one or more than one card comprises predetermined optically readable indicia. 
     
     
         5 . The biochip of  claim 3 , wherein the biochip comprises x stackable card/gasket pairs, wherein x is an integer from one to 100,000. 
     
     
         6 . The biochip of  claim 3 , wherein the plurality of apertures between one and 1536. 
     
     
         7 . The biochip of any of  claim 3 , wherein each card and gasket of the stackable card/gaskets has an equal to the number of apertures. 
     
     
         8 . An automated or semi-automated analyzer comprising:
 a biochip having a plurality of releasably attached card/gasket pairs, wherein each card of the card/gasket pairs comprises a bioactive material or agent and each of the card/gasket pairs has an aligned array of apertures extending therethrough, wherein the aligned apertures define microfluidic flow channels, with a portion of a horizontal surface of each card defining at least one analytical site in the channels;   a fluid delivery system in communication with an upper or lower portion of the biochip for flowing fluid samples through the biochip;   a signal reader configured to engage at least one analytical site of a card of the biochip and detect a signal from the analytical site;   a card holder member configured to releasably serially engage the card/gasket pairs and present the card to the signal reader; and   a control circuit configured to communicate with the signal reader and the card holder to direct automated operation of the card holding member.   
     
     
         9 . An analyzer according to  claim 8 , wherein the signal reader is in communication with or comprises an analyzer that programmatically analyzes the obtained signal and compares the signal to an electronic library of reference signals. 
     
     
         10 . The analyzer of  claim 8 , wherein the control circuit comprises a controller that is configured to direct the signal reader to obtain signal from a region of a respective card that comprises predetermined authenticity or test data indicia. 
     
     
         11 . An automated method of analyzing multiple fluid samples exposed to multiple analytical sites in a single biochip, comprising:
 a) introducing fluid samples into an automated bioanalyzer;   b) flowing the introduced fluid samples through a biochip having a plurality of releasably attached card/gasket pairs, each of the card/gasket pairs having an aligned array of apertures extending therethrough, wherein sets of the apertures define microfluidic flow channels, wherein at least one card of the biochip comprises at least one bioactive material that contacts a sample flowing thereover and defines at least one analytical site in the channels;   c) serially presenting a card of the biochip to a signal reader;   d) obtaining a signal from at least one analytical site of the presented card; and   e) analyzing the obtained signal to determine the presence or absence of an analyte.   
     
     
         12 . The method of  claim 11 , wherein the bioactive material comprises one or more of the following: an antibody, an antigen, a nucleic acid, a peptide nucleic acid, a ligand, a receptor, avidin, biotin, Protein A, Protein G, Protein L, a substrate for an enzyme and any combination thereof. 
     
     
         13 . The method of  claim 11 , wherein the bioactive material is an antigen and a signal is detected if an antigen/antibody complex is formed. 
     
     
         14 . The method of  claim 11 , wherein the bioactive material is an antibody and a signal is detected if an antigen/antibody complex is formed. 
     
     
         15 . The method of  claim 11 , wherein the bioactive material is a nucleic acid or peptide nucleic acid and a signal is detected if a hybridization complex is formed.