Chromatographic-like separation using sample droplet ejection
Disclosed are methods for separating target and non-target analytes in a sample. The methods can utilize an acoustic droplet ejector (ADE) and an open port interface (OPI) to achieve liquid chromatography (LC)-like separation for an analytical instrument such as, for example, a mass spectrometer.
1 . A method comprising:
combining separation media with a sample solution;
separating the separation media from the sample solution;
retaining the separation media in a reservoir containing an eluent to form an eluent solution having an eluent concentration;
generating a synthetic chromatogram by repeatedly:
ejecting a volume of eluent solution from the reservoir into a sampling interface,
capturing the volume of eluent solution with the sampling interface and transferring the captured volume to a mass spectrometer for mass analysis,
mass analyzing eluent ions, and
increasing the eluent concentration of the eluent solution until a target concentration is reached.
2 . The method of claim 1 , wherein the volume of eluent solution is ejected using an acoustic droplet ejector (ADE), a microinjector, a nanoinjector, or an inkjet printer nozzle.
3 . The method of claim 1 , wherein increasing the eluent concentration of the eluent solution comprises adding eluent to the eluent solution.
4 . The method of claim 1 , wherein increasing the eluent concentration of the eluent solution further comprises mixing the separation media.
5 . The method of claim 1 , wherein combining separation media with sample solution further comprises mixing.
6 . The method of claim 1 , wherein retaining the separation media in a reservoir or a plurality of reservoirs containing an eluent further comprises mixing.
7 . The method of claim 4 , wherein the mixing comprises electromagnetic mixing, mechanical agitation, or acoustic agitation to the reservoir.
8 . The method of claim 1 , wherein the sampling interface comprises an open port interface (OPI).
9 . The method of claim 1 , wherein the ejecting comprises ejecting one or more discrete droplets of eluent solution.
10 . The method of claim 1 , wherein the capturing the volume of eluent solution further comprises diluting the captured volume of eluent solution.
11 . The method of claim 1 , wherein the separation media comprises a solid phase media, a microparticle, a nanoparticle, a magnetic particle, an ion exchange moiety, a chelating moiety, a hydrophobic moiety, an affinity moiety, or a size exchange moiety.
12 . The method of claim 11 , wherein the separation media comprises a solid phase media that comprises a particle comprising an active surface coating or a resin.
13 . The method of claim 1 , wherein the retaining step comprises applying a magnetic field to the sample reservoir.
14 . The method of claim 1 , wherein the eluent comprises an organic compound, an ionic solution, or a binding agent that binds to an affinity resin.
15 . The method claim 1 , wherein increasing the concentration of the eluent solution comprises adding eluent using an acoustic ejector, a microinjector, a nanoinjector, or an inkjet printer nozzle.
16 . The method of claim 1 , wherein the reservoir or plurality of reservoirs comprises a sample well plate operatively configured to an ADE.
17 . The method of claim 1 , wherein the method separates two or more components in the sample solution.
18 . A method comprising:
combining separation media with a sample solution;
separating the separation media from the sample solution;
retaining the separation media in a plurality of reservoirs, each reservoir containing a different concentration of an eluent to form a plurality of eluent solutions at different eluent concentrations;
generating a synthetic chromatogram by:
sequentially ejecting from each reservoir of the plurality of reservoirs a volume of eluent solution into a sampling interface,
capturing the volume of eluent solution with the sampling interface and transferring the captured volume to a mass spectrometer to generate eluent ions for mass analysis, and
mass analyzing the eluent ions.
19 . The method of claim 18 , wherein the sampling interface comprises an open port interface (OPI).
20 . The method of claim 18 , wherein the volume of eluent solution is ejected using an acoustic droplet ejector (ADE), a microinjector, a nanoinjector, or an inkjet printer nozzle.