Method and system for producing laser ablation plumes without ablation recoil products

Patent metadata

Field	Value
Publication number	US-10622201-B2
Application number	US-201716320976-A
Country	US
Kind code	B2
Filing date	Jul 25, 2017
Priority date	Jul 25, 2016
Publication date	Apr 14, 2020
Grant date	Apr 14, 2020

Abstract

A method for preparing thin layers from liquid samples is disclosed. Such thin layers can be useful when analyzing samples with probes whose penetration length in these samples is short The method consists of squeezing a certain amount of a liquid sample between two approximately flat and parallel surfaces separated by a small distance then cooling down the liquid sample until it freezes in a way that the frozen sample adheres only to one of these two flat surfaces. Removing the non-adhered flat surface leaves the frozen sample layer with the thickness approximately equal to the initial distance between the two parallel surfaces.

First claim

Therefore what is claimed:

1. A method of laser ablation of a liquid sample which avoids production of ablation recoil products, comprising the steps of:
a) preparing a thin solid layer of a liquid sample by
i) providing a substrate member having a flat surface and a cover member having a flat surface, and one of said substrate and cover members having spacers of preselected thickness on its flat surface such that when said substrate and cover members are aligned and mated with said flat surfaces facing each other said substrate and cover members are separated by distance equal to the preselected thickness of said spacers,
ii) depositing a sample volume of the liquid sample on the flat surface of the substrate member and mating the cover member to the substrate member to sandwich the liquid sample between the flat surfaces, and securing the substrate and cover member together;
b) cooling the substrate and cover members to a temperature below a freezing point of the liquid sample to freeze the liquid sample thereby forming a solid thin film of liquid sample of thickness substantially equal to the preselected thickness of said spacers;
c) removing the cover member to expose the frozen thin film of sample;
d) irradiating the exposed frozen thin film of sample with a pulsed laser, said preselected thickness of the frozen thin film of sample is selected such that an absorption length of light emitted by the pulsed laser in the frozen thin film of sample is of an order of the preselected thickness such that an ablation plume of the sample is released from the frozen thin film of sample which is characterized by a lack of ablation recoil products.

2. The method according to claim 1 , where the cover member further comprises a non-adhesive coating at its flat surface where said non-adhesive coating facilitates detachment of said cover member from said frozen thin film of sample.

3. The method according to claim 1 , where said freezing of the liquid sample is assisted by a disturbance device that creates a mechanical disturbance within said thin film of sample layer during the supercooling phase of said freezing process.

4. The method according to claim 3 , where said disturbance device is an ultrasonic transducer.

5. The method according to claim 3 , where said disturbance device is a pulsed laser that emits a laser pulse where said laser pulse gets absorbed within said supercooled thin film of sample thus creates a non-uniform thermo-elastic profile within said supercooled thin film of sample and where relaxation of said thermoelastic profile creates a disturbance that causes freezing of said thin film of sample.

6. The method according to claim 1 , further comprising directing a flow of a gaseous mixture above the frozen sample, and wherein said gas flow contains molecules that are mostly present in the vapor that evaporates from said frozen sample layer and where partial pressures of said molecules in said gas flow are approximately equal to the saturation vapor pressure of said molecules immediately above the said frozen sample layer thus stabilizing the thickness and composition of said frozen sample layer.

7. The method according to claim 1 , wherein said liquid sample is a biosample liquid.

8. The method according to claim 7 , wherein the biosample liquid is any one of blood, serum, plasma, saliva, urine and cerebrospinal fluid (CSF).

9. The method according to claim 1 , further comprising positioning a detector in proximity to said substrate such that upon production of the laser ablation plume, said detector is configured to detect selected properties of said laser ablation plume.

10. The method according to claim 9 wherein said detector is a mass spectrometer, and including directing an ionizing agent towards the laser ablation plume wherein ionizing agent ionizes at least some of the molecules of the laser ablation plume, and wherein said mass spectrometer is positioned to intercept ionized molecules of the laser ablation plume where they are analyzed by said mass spectrometer.

11. The method according to claim 10 wherein said ionizing agent is based on electrospray ionization (ESI); atmospheric pressure chemical ionization (APCI); atmospheric pressure photoionization (APPI); or photo-ionization.

12. The method according to claim 10 , where an additional electromagnetic system is introduced that create electric or magnetic fields that facilitate an ionization process.

13. The method according to claim 12 , where said electromagnetic system creates delayed extraction effect.

14. The method according to claim 10 where said plume created through said laser ablation is ejected and probed within vacuum.

15. The method according to claim 10 where said plume created through said laser ablation is ejected and probed within vacuum.

16. The method according to claim 10 where said plume created through said laser ablation is ejected and probed within a surrounding gas that has the pressure level close to the standard atmospheric pressure level.

17. A method of laser ablation of a liquid sample which avoids production of ablation recoil products, comprising the steps of:
a) preparing a thin solid layer of a liquid sample by
i) providing a substrate member having a flat surface and a cover member having a flat surface, and one of said substrate and cover members having spacers of preselected thickness on its flat surface such that when said substrate and cover members are aligned and mated with said flat surfaces facing each other said substrate and cover members are separated by distance equal to the preselected thickness of said spacers,
ii) depositing a sample volume of the liquid sample on the flat surface of the substrate member and mating the cover member to the substrate member to sandwich the liquid sample between the flat surfaces, and securing the substrate and cover member together;
b) cooling the substrate and cover members to a temperature below a freezing point of the liquid sample to freeze the liquid sample thereby forming a solid thin film of liquid sample of thickness substantially equal to the preselected thickness of said spacers;
c) heating the cover member up to a melting point temperature of the solid thin film of sample such that a surface of the frozen thin film of sample in contact with the optically flat surface of the cover member melts;
d) removing the cover member to expose the frozen thin film of sample;
e) irradiating the exposed frozen thin film of sample with a pulsed laser, said preselected thickness of the frozen thin film of sample is selected such that an absorption length of light emitted by the pulsed laser in the frozen thin film of sample is of an order of the preselected thickness such that an ablation plume of the sample is released from the frozen thin film of sample which is characterized by a lack of ablation recoil products.

Assignees

• Franjic Kresimir
• Synaptive Medical Barbados Inc

Inventors

• Franjic Kresimir

Classifications

• G01N1/286

  involving mechanical work, e.g. chopping, disintegrating, compacting, homogenising (microtomes G01N1/06; pulverising in general B02C; mixing in general B01F) · CPC title

• H01J49/0463

  Desorption by laser or particle beam, followed by ionisation as a separate step (sample holder per se H01J49/0418) · CPC title

• H01J49/168

  field ionisation, e.g. corona discharge (atmospheric pressure corona discharge per se H01T19/00) · CPC title

• H01J49/165

  Electrospray ionisation · CPC title

• H01J49/145

  using chemical ionisation · CPC title