Pressure driven fluidic injection for chemical separations
Methods, systems and devices that allow independently applied pressures to a BGE reservoir and a sample reservoir for pressure-driven injection that can inject a discrete sample plug into a separation channel that does not require voltage applied to the sample reservoir and can allow for in-channel focusing methods to be used. The methods, systems and devices are particularly suitable for use with a mass spectrometer.
1. A method of sample processing, comprising:
providing a microfluidic device with at least one separation channel in fluid communication with a background electrolyte (BGE) reservoir, and a sample reservoir connected to the separation channel through a sample channel;
injecting a fluid sample from the sample reservoir into the at least one separation channel by concurrently applying pressurized gas to the BGE reservoir and the sample reservoir;
delivering fluid from the BGE reservoir into the at least one separation channel to define a plug of the sample in the at least one separation channel by reducing a gas pressure in the sample reservoir, so that a gas pressure in the BGE reservoir is greater than the gas pressure in the sample reservoir;
concentrating an analyte component of the sample within the at least one separation channel; and
performing at least one of:
(a) electrospraying the concentrated analyte component from at least one emitter in fluid communication with the at least one separation channel; and
(b) measuring an electrical signal corresponding to the concentrated analyte component in or emerging from the separation channel.
2. The method of claim 1 , wherein the microfluidic device comprises a waste reservoir connected to the separation channel through a waste channel, the method further comprising maintaining a gas pressure differential between the sample reservoir and the waste reservoir to inject the fluid sample.
3. The method of claim 2 , wherein the waste reservoir is connected to the at least one separation channel at a location downstream from a location at which the sample channel is connected to the at least one separation channel.
4. The method of claim 1 , wherein concentrating the analyte component comprises performing transient isotachophoresis to concentrate the analyte component.
5. The method of claim 4 , comprising introducing a leading electrolyte solution into the sample prior to injecting the sample.
6. The method of claim 5 , wherein the leading electrolyte solution has a higher electrophoretic mobility than the analyte component of the sample.
7. The method of claim 5 , wherein the leading electrolyte solution comprises a concentration of an electrolyte species that is at least 5 times larger than a concentration of the electrolyte species in the sample.
8. The method of claim 4 , comprising introducing a leading electrolyte solution into the at least one separation channel prior to injecting the sample.
9. The method of claim 8 , wherein the leading electrolyte solution has a higher electrophoretic mobility than the analyte component of the sample.
10. The method of claim 1 , wherein the injecting is performed without applying a voltage to the sample reservoir.
11. The method of claim 1 , comprising adjusting a duration of the pressure applied to at least one of the sample reservoir and the BGE reservoir to adjust a volume of the injected sample.
12. The method of claim 1 , comprising clearing a trailing end of the injected sample from the sample channel and flowing fluid from the BGE reservoir into the at least one separation channel to inject the sample as a plug.
13. The method of claim 12 , wherein clearing the trailing end of the injected sample comprises applying a higher gas pressure to the BGE reservoir than to the sample reservoir.
14. The method of claim 1 , further comprising discharging the concentrated analyte component from the microfluidic device via at least one emitter on the microfluidic device toward at least one of a collection device or an entrance of a mass spectrometer.
15. The method of claim 14 , comprising discharging the concentrated analyte component by electro-osmotic pumping.
16. The method of claim 1 , wherein the gas pressure within the BGE reservoir and the sample reservoir during the injection of the sample are each between 0.1 psi and 50 psi.
17. The method of claim 1 , wherein reducing the gas pressure in the sample reservoir comprises venting gas from the sample reservoir.
18. The method of claim 1 , wherein the sample comprises at least one member of the group consisting of amino acids, polar metabolites, charged molecules, peptides, and proteins.
19. The method of claim 1 , wherein one or more components of the sample are derived from at least one member of the group consisting of biofluids, blood, serum, urine, dried blood, cell growth media, lysed cells, beverages, and food.
20. The method of claim 1 , wherein the measured electrical signal corresponds to ions of the concentrated analyte component.