IP Library Granted Patent US 12,013,391
Granted Patent B2
US 12,013,391 · App. 16/383,241 · Granted Jun 18, 2024

Stabilized cell acquisition for elemental analysis

Inventors: Vladimir Baranov (Richmond Hill, CA); Alexander Loboda (Thornhill, CA); Michael Sullivan (Ontario, CA)
Assignee: STANDARD BIOTOOLS CANADA INC.
G01N33/5306G01N33/58H01J49/105G01N2458/15G01N2560/00
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Quick Facts
Patent No.
US 12,013,391
App. No.
16/383,241
Granted
Jun 18, 2024
Kind
B2
Abstract

Analyzing samples injected into an inductively coupled plasma source can be improved by one or more of a stabilizing solution mixable with a sample prior to injection and a heated injector. The stabilizing solution can minimize the difference in osmotic pressure between the solution and the cells with a relatively low amount of dissolved solids (e.g., at or below about 0.2%). The stabilizing solution can contain a salt (e.g., ammonium nitrate) present in concentrations of at least 5 mM. The injector can be heated before and/or during injection. In some cases, heat from adjacent parts can be channeled into the injector to improve heating of the injector. An injector heated to sufficient temperatures can minimize solute buildup and can extend the usable time between cleanings. These improvements can be especially useful in elemental analysis, such as inductively coupled plasma mass spectrometry or inductively coupled plasma optical emission spectrometry.

Claims (28)

1. A sample-making kit, comprising element-tagged affinity reagent comprising an affinity reagent capable of specifically binding to an analyte and a metal-binding moiety bound to one or more metal elements; and

a stabilizing solution having a total dissolved solids at or below approximately 0.2%, wherein the stabilizing solution has a pH of between 5-9 and comprises a salt, wherein:

the salt is present in concentrations of 5 mM to 25 mM,

the salt is ammonium nitrate, and

the stabilizing solution prevents or reduces signal drop and deposition of the salt on an injector configured to convey a sample solution comprising the analyte, the element-tagged affinity reagent, and the stabilizing solution to an inductively coupled plasma.

2. The sample-making kit of claim 1 , wherein the affinity reagent is bindable to surface of whole cells.

3. The sample-making kit of claim 2 , wherein the stabilizing solution induces sufficiently low osmotic pressure on membranes of whole cells bound to the affinity reagent to avoid osmotic lysis of the whole cells.

4. The sample-making kit of claim 1 , wherein the metal-binding moiety includes a polymer linked to the affinity reagent and comprising at least one metal-binding pendant group that comprises at least one metal atom.

5. A method, comprising

providing an element-tagged analyte, wherein the element-tagged analyte comprises a sample containing whole cells each bound to an element-tagged affinity reagent, wherein each of the element-tagged affinity reagents comprises an affinity reagent and a metal-binding moiety wherein the affinity reagent is bound to the whole cell and the metal binding moiety is bound to one or more metal elements; and

mixing the element-tagged analyte with a stabilizing solution having a pH of between 5-9 and having a total dissolved solids at or below approximately 0.2%, wherein:

the stabilizing solution comprises a salt,

the salt is present in concentrations of 5 mM to 25 mM,

the salt is ammonium nitrate, and

the stabilizing solution prevents or reduces signal drop and deposition of the salt on an injector configured to convey a sample solution comprising the analyte, the element-tagged affinity reagent, and the stabilizing solution to an inductively coupled plasma.

6. The method of claim 5 , further comprising passing the stabilizing solution through the injector heated to a temperature of at least 100° C.

7. The sample-making kit of claim 1 , wherein the stabilizing solution does not comprise carbon.

8. The sample-making kit of claim 1 , wherein the stabilizing solution does not comprise a metal having an atomic mass unit greater than 80.

9. The sample-making kit of claim 1 , wherein the element-tagged affinity reagent comprises 145Nd-CD4.

10. The sample-making kit of claim 1 , wherein the salt is present in a concentration of 25 mM.

11. The sample-making kit of claim 1 , wherein the stabilizing solution has the total dissolved solids at or below 0.1%.

12. The sample-making kit of claim 1 , wherein the stabilizing solution further comprises one or more salts selected from the group consisting of ammonium acetate, ammonium phosphate, and ammonium formate.

13. The sample-making kit of claim 1 , wherein the one or more metal elements of the element-tagged affinity reagent is selected from the group consisting of 145Nd, 146Nd, 147Sm, 155Gd, 159Tb, 160Gd, and 171Yb.

14. The sample-making kit of claim 1 , wherein the affinity reagent is selected from the group consisting of an aptamer, a lectin, and a polysaccharide.

15. The sample-making kit of claim 1 , wherein the metal binding moiety of the element-tagged affinity reagent is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) or diethylenetriaminepentaacetic acid (DTPA).

16. The sample-making kit of claim 1 , wherein the stabilizing solution further comprises an azide-based salt.

17. The sample-making kit of claim 1 , further comprising a sample, wherein the stabilizing solution is mixed with the sample.

18. The sample-making kit of claim 17 , wherein the sample is a biological sample.

Assignments (2)
CHANGE OF NAME Recorded Sep 15, 2022
From: FLUIDIGM CANADA INC.
To: STANDARD BIOTOOLS CANADA INC.
Reel/Frame 062078/0806 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 11, 2019
From: BARANOV, VLADIMIR; LOBODA, ALEXANDER; SULLIVAN, MICHAEL
To: FLUIDIGM CANADA INC.
Reel/Frame 049437/0767 →
Continuity (2)
Provisional Application 62657332 · Apr 13, 2018
Related Publication 20190317082A1 · Oct 17, 2019