Library Screen Protocol

 

 

á      Turn on hybridization oven (Fisher isotemp 13 247 31) and heat to 58¡C

á      Label the appropriate number of 300mm hybridization tubes (no more than 7 filters per tube)

 

á      Add 75ml Church buffer (see recipies) to each tube and place in the hybridization oven for at least 30 minutes

 

á      Heat 1L of church buffer to about 60¡C and place the filters facing down into a Clear Magazine Snap Case (14Óx 8 5/8Óx 3 7/8Ó The Container Store 584070).  Pour the church buffer over the filters into the container.  Flip the filters individually in order to ensure the filters are not sticking together and will hybridize properly.  They now should have the labels and DNA facing up.

 

á      Roll the filters up with the stamping and labeling facing inward and place into hybridization tubes (Fisher 13 247 300) and clearly label the tubes.  Multiple filters can be placed into the same tube, up to about 7 per tube.  The pre-hybridization church buffer in the container can be reused several times, so pour back into a 1L bottle. 

 

á      Incubate in oven for a minimum of 3 hours while labeling primers.  Make sure the filters unroll so they lay against the sides of the tubes.    If not, reverse the direction of the hybridization bottle. 

 

á      Set up labeling reaction (see Overgo worksheet)

 

á      To each hybridization bottle, add denatured anchor probe and test probe.  Typically, about 40ml of probe and 10µl of anchor.  Let incubate overnight at 58¡C.

 

á      Before the washes the next morning, for every two hybridization bottles, microwave one liter of 1.5X SSC/ 0.1% SDS for 3 minutes and place into a 62¡C water bath until ready for use. 

 

á      Empty the hybridization solution into radioactive liquid waste and add 150ml 2X SSC/ 0.1% SDS to each of the hybridization bottles.  Tighten the caps and place in the hybridization oven at 58¡C for 15 minutes.

 

á      While washing, place the 2 Pyrex Portables hot packs in the microwave for 3 minutes and 30 seconds.  Then place in the bottom of the Pyrex portable to heat the inside (see below if there is no shaking incubator available).

 

á      Empty the 2X wash into the radioactive liquid waste

 

á      With a long set of forceps (Fisher 10 316B), pull the filters out of the hybridization bottles and into the constructed Rubbermaid box.  13 is about the maximum number of filters per box.

 

á       For this next step we recommend a shaking water bath at 58¡C.  If this is not available, an insulated container can be constructed that maintains the temperature for the 30 minutes. Using a Clear Magazine Snap Case (14Óx 8 5/8Óx 3 7/8Ó The Container Store 584070), cut the two hinges from the top of the box so it will detach completely.  Cut a piece of packing Styrofoam to tightly fit into the lid.  Place the Styrofoam In a large Ziploc bag and wedge into the lid of the box.  Take a 15ml conical tube (Corning 430053) and cut in half.  Cut a hole in the lid of the box that goes through the Styrofoam and the Ziploc bag exactly the size of the conical tube (be sure it is not any larger so the lip on the tube will prevent the tube from going all the way through the hole.  Next slide the half of the tube with the cap through the hole all the way up to the lid and seal around the tube with a glue gun.  Get a funnel that fits in the conical tube.  Lastly, get  a 5 piece Pyrex Portable  with the hot packs and place the box inside for insulation.

 

á      Pour a little 2X SSC/ 0.1% SDS over the filters so they are a little manageable.  Flip the filters one by one so they face down trying to lay them stacked on one another.  This will prevent sticking of the filters to one another so they all get properly washed. 

 

á      Place the lid on the box and place inside the Pyrex Portable on top of the hot packs.  Remove the cap on the conical tube and place the funnel into the tube. 

 

á      Pour the 1.5X SSC/ 0.1% SDS into the funnel as quickly as possible to prevent the wash from cooling down.  Quickly remove the funnel and replace the cap in order to zip up the container.

 

á      Place on an orbital shaker (Fisher 14 512 24) for 30 minutes

 

á      As soon as you have the 2nd wash shaking, place the same amount of 1.0x SSC/ 0.1% SDS into the microwave (about 3 minutes for 1L and 5 minutes for 2 liters) to heat just above 58¡C then place in a water bath set at 62¡C until ready to use.

 

á      Repeat wash with 1.0x SSC using the same procedure as above

 

 

á      Cut a piece of blotting paper to fit the inside of the imaging cassette (Amersham RPN11643).  Tape the covered filter face up on to the filter paper.  Place the imaging screen (Amersham 63-0034-90) face down on to the covered filter and close the cassette for exposure.   Filters from ChildrenÕs Hospital Oakland Reasearch Institute, should be oriented with the pencil labeling across the top.  Filters from Arizona Genomics Institute and Clemson University Genomics Institute should be oriented with the serial number and filter label in the bottom right corner.  There is a difference in stamping and this will compensate when scoring the filters using Comboscreen.