Automated Protein Precipitation and/or Dispersive Solid Phase Extraction Using Filter Tips

A method of automated dispersive solid phase extraction, comprising:

• a) introducing a sample containing at least one target compound in a first sample well on a robotic liquid handler sample tray, wherein said first sample well contains a sorbent;
• b) mixing said sorbent and sample by repeatedly aspirating and dispensing with a top pipette tip attached to a motorized pipettor on a robotic liquid handler to load the target compounds onto said sorbent;
• c) aspirating said sorbent and sample into said top pipette tip;
• d) moving said top pipette tip with the robotic liquid handler to a pipette tip tray having at least one filter pipette tip;
• e) inserting said top pipette tip into a filter pipette tip to form a tip-on-tip device, wherein the filter pipette tip contains a screen or porous frit at a distal delivery end and a gasket at or below a hub at a proximal end, wherein said top pipette tip contacts said filter pipette tip at said gasket to form an air-tight seal between said top pipette tip and said filter pipette tip;
• and,
• f) dispensing said sorbent and sample through said filter pipette tip and into a second sample well to form a second solution, wherein said sorbent is retained by said screen or porous frit in said filter pipette tip.

A method of automated protein precipitation, comprising:

• a) introducing a biological sample containing protein in a first sample well on a robotic liquid handler sample tray;
• b) introducing a precipitation reagent in a second sample well on a robotic liquid handler sample tray;
• c) aspirating said biological sample containing protein into a wide bore pipette tip attached to a motorized pipettor on a robotic liquid handler;
• d) moving said wide bore pipette tip with the robotic liquid handler to a pipette tip tray having at least one filter pipette tip;
• e) inserting said wide bore pipette tip into a filter pipette tip, wherein the filter pipette tip contains a substrate and at least one screen or filter, such that a pressure fit forms between said wide bore pipette tip and said filter pipette tip to form a tip-on-tip device;
• f) moving said tip-on-tip device with the robotic liquid handler to said second sample well;
• g) dispensing said biological sample containing protein from said wide bore pipette tip onto said substrate in said filter pipette tip;
• h) aspirating said precipitating reagent into tip-on-tip device;
• i) mixing said precipitation reagent, said biological sample, and said substrate inside the filter tip by aspirating air to form a first mixture;
• j) dispensing said first mixture into said first or second sample well, and then repeatedly aspirating and dispensing said precipitation reagent and biological sample with said tip-on-tip device to form a protein precipitate/substrate solid and a first solution, wherein said first solution is substantially free of protein;
• and,
• k) dispensing said first solution through said tip-on-tip device and into the second sample well to form a second solution.

A device for robotic filtration comprising:

• a) a bottom pipette tip having a first distal delivery end opposite of a first hub, said hub sized so that said bottom pipette tip can be fitted to a robotic liquid handler;
• b) said bottom pipette tip having a filter inside bottom pipette tip located below said first hub and near said first distal delivery end;
• c) a top pipette tip having a second distal delivery end opposite a second hub, said hub sized so that said top pipette tip can be fitted to said robotic liquid handler;
• d) a gasket on either the inner surface of said bottom pipette tip located below said first hub and above said filter or on the outer surface of said top pipette tip;
• e) wherein said top pipette tip and said bottom pipette top are sized and shaped so that said top pipette tip can be inserted into said bottom pipette tip such that an outer surface of said second distal delivery end contacts said bottom pipette tip at said gasket to form an air-tight seal that can be made and removed with less than 10 Newtons of force and said top pipette tip does not reach said filter.