# US 2019/0170705 A1 · Encapsulated pre-analytic workflows for flow-through devices, liquid chromatography and mass spectrometric analysis

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- Number: US 2019/0170705 A1
- Document ID: US20190170705A1
- Status: Published application
- Kind: A1
- Application number: 16/321,222
- Filed: 2017-07-28
- Published: 2019-06-06
- Earliest claimed: 2016-07-28
- Assignees: Waters Technologies Corporation
- Applicants: Waters Technologies Corporation
- Inventors: Kevin Daniel Wyndham; Darryl W. Brousmiche
- Web page: https://patentgrep.com/patent/US20190170705A1

## CPC

- G01N 30/06: Preparation
- G01N 30/50: Conditioning of the sorbent material or stationary liquid
- G01N 30/72: Mass spectrometers {(mass spectrometers per se H01J49/00)}
- G01N 30/7233: {interfaced to liquid or supercritical fluid chromatograph (interfaces in general for introducing or extracting samples to be analysed with specially adapted mass spectrometer, see H01J49/04)}
- G01N 30/88: Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
- G01N 2030/521: {form}
- G01N 2030/524: {structural properties}
- G01N 2030/8822: {involving blood}
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

This invention relates to encapsulated workflow reagents comprising an encapsulating material and a workflow reagent encapsulated within the encapsulating material for sample and workflow preparation prior to chromatographic, spectroscopic or other analytical systems, use thereof, and devices comprising the same.

## Claims

### Claim 1

An encapsulated workflow reagent comprising an encapsulating material and a workflow reagent encapsulated within the encapsulating material.

### Claim 2 (depends on 1)

The encapsulated workflow reagent according to claim 1, wherein the encapsulating material is attached to a surface of a scaffolding material.

### Claim 3 (depends on 1)

The encapsulated workflow reagent according to claim 1, wherein the workflow reagent encapsulated within the encapsulating material is attached to or adsorbed onto the surface of a chromatographic material.

### Claim 4 (depends on 1)

The encapsulated workflow reagent according to claim 1, wherein the encapsulating material is one or more polymers capable of providing a controlled release of the workflow reagents.

### Claim 5 (depends on 2)

The encapsulated workflow reagent according to claim 2, wherein the scaffolding material is a solid, a porous solid, a non-porous solid, a macroporous solid, a mesoporous solid, a microporous solid, a nanoporous solid, a superficially porous solid, a perfusive solid, a controlled pore solid, an amorphous solid, a radially aligned porous solid, a non-radially aligned porous solid, a circular ordered porous solid, a crystalline solid, a sintered solid, a liquid, a hydrogel, an aerogel, a xerogel, a cryo-gel, a soft-gel, a gel-like material, a wall-anchored monolith, a wall-anchored polymeric high internal phase material, a particle, a monolith, a membrane, a poly-HIPE, a mesh, a fiber, a screen, an anodized filter, or a frit-like material.

### Claim 6 (depends on 3)

The encapsulated workflow reagent according to claim 3, wherein the chromatographic material is a solid, a porous solid, a non-porous solid, a macroporous solid, a mesoporous solid, a microporous solid, a nanoporous solid, a superficially porous solid, a perfusive solid, a controlled pore solid, an amorphous solid, a radially aligned porous solid, a non-radially aligned porous solid, a circular ordered porous solid, a crystalline solid, a sintered solid, a hydrogel, an aerogel, a xerogel, a cryo-gel, a soft-gel, a gel-like material, a particle material, or a monolith material.

### Claim 7 (depends on 2)

The encapsulated workflow reagent according to claim 2, wherein the encapsulated workflow reagent material has the formula
[(B)—(Y)n)]o-EM (Formula I)
EM represents the encapsulating material;
B represents a scaffolding material;
Y is a linker group between the encapsulating material and a surface of the scaffolding material;
o is an integer greater than or equal to 0; and
n is an integer greater than or equal to 1.

### Claim 8 (depends on 7)

The encapsulated workflow reagent according to claim 7, wherein the linker group is of the formula represented by Formula II
wherein
n1 an integer from 0-30;
n2 an integer from 0-30;
each occurrence of R1, R2, R3 and R4 independently represents hydrogen, fluoro, methyl, ethyl, n-butyl, t-butyl, i-propyl, lower alkyl, a protected or deprotected alcohol, a zwiterion, or a group Z;
Z represents:
a) a surface attachment group having Formula III:
(B1)x(R5)y(R6)zSi— Formula III:
wherein x is an integer from 1-3,
y is an integer from 0-2,
z is an integer from 0-2,
and x+y+z=3
each occurrence of R5 and R6 independently represents methyl, ethyl, n-butyl, iso-butyl, tert-butyl, iso-propyl, thexyl, substituted or unsubstituted aryl, cyclic alkyl, branched alkyl, lower alkyl, a protected or deprotected alcohol, or a zwiterion group;
B1 represents —OR7, —NR7′R7″, —OSO2CF3, or —Cl; where each of R7′ R7′ and R7″ represents hydrogen, methyl, ethyl, n-butyl, iso-butyl, tert-butyl, iso-propyl, thexyl, phenyl, branched alkyl or lower alkyl;
b) an attachment to a surface group through a direct carbon-carbon bond formation or through a heteroatom, ester, ether, thioether, amine, amide, imide, urea, carbonate, carbamate, heterocycle, triazole, or urethane linkage; or
c) an adsorbed, surface group that is not covalently attached to the surface of the material;
Y′ represents a direct bond; a heteroatom linkage; an ester linkage; an ether linkage; an thioether linkage; an amine linkage; an amide linkage; an imide linkage; a urea linkage; a thiourea linkage; a carbonate linkage; a carbamate linkage; a heterocycle linkage; a triazole linkage; a urethane linkage; a diol linkage; a polyol linkage; an oligomer of styrene, ethylene glycol, or propylene glycol; a polymer of styrene, ethylene glycol, or propylene glycol; a carbohydrate group, a multi-antennary carbohydrates, a dendrimer or dendrigraphs, or a zwitterion group; and
A represents attachment to the encapsulating material by a ionic group, non-covalently attachment group or by a direct bond including (but not limited to): a heteroatom linkage; an ester linkage; an ether linkage; an thioether linkage; an amine linkage; an amide linkage; an imide linkage; a urea linkage; a thiourea linkage; a carbonate linkage; a carbamate linkage; a heterocycle linkage; a triazole linkage; a urethane linkage; a diol linkage; a polyol linkage; an oligomer of styrene, ethylene glycol, or propylene glycol; a polymer of styrene, ethylene glycol, or propylene glycol; a carbohydrate group, a multi-antennary carbohydrates, a dendrimer or dendrigraphs, or a zwitterion group.

### Claim 9 (depends on 1)

The encapsulated workflow reagent according to claim 1, wherein the workflow reagent is an enzyme, a surfactant, a labeling reagent, a reactive compound, an internal standard, an external standard or a combination thereof.

### Claim 10 (depends on 1)

The encapsulated workflow reagent according to claim 1, wherein the workflow reagent is released over a period of time.

### Claim 11 (depends on 2)

The encapsulated workflow reagent according to claim 2, wherein the primary encapsulation shell further encapsulates one or more additional encapsulation shells comprising one or more independent workflow reagents.

### Claim 12 (depends on 11)

The encapsulated workflow reagent according to claim 11, wherein the one or more additional encapsulation shells are in the form of microcapsules separately contained within the primary encapsulation shell.

### Claim 13 (depends on 12)

The encapsulated workflow reagent according to claim 12, wherein the one or more additional workflow reagents are released at the same time.

### Claim 14 (depends on 12)

The encapsulated workflow reagent according to claim 12, wherein the one or more additional workflow reagents are released sequentially.

### Claim 15 (depends on 11)

The encapsulated workflow reagent according to claim 11, wherein the one or more additional encapsulation shells are in the form of concentric encapsulation shells such that the workflow reagents are sequentially released.

### Claim 16 (depends on 1)

A sample preparation device comprising an encapsulated workflow reagent according to claim 1.

### Claim 17 (depends on 16)

The sample preparation device according to claim 16, wherein the device is selected from the group consisting of chromatographic columns, thin layer plates, filtration membranes, sample cleanup devices and microtiter plates; packings for HPLC columns; solid phase extraction (SPE); ion-exchange chromatography; magnetic bead applications; affinity chromatographic and SPE sorbents; sequestering reagents; solid supports for combinatorial chemistry; solid supports for oligosaccharide, polypeptides, and/or oligonucleotide synthesis; solid supported biological assays; capillary biological assay devices for mass spectrometry, templates for controlled large pore polymer films; capillary chromatography; electrokinetic pump packing materials; packing materials for microfluidic devices; polymer additives; catalysis supports; and packings materials for microchip separation devices.

### Claim 18 (depends on 1)

A method for a method for preparing a sample for analysis comprising the steps of:
providing a sample preparation device comprising an encapsulated workflow reagent according to claim 1;
introducing a sample to the sample preparation material; and
allowing the sample to remain with the sample preparation material for sufficient time to release the encapsulated workflow reagent.

### Claim 19 (depends on 18)

The method for a method for preparing a sample for analysis according to claim 18 further comprising adding a pore forming agent to induce release of the encapsulated workflow reagent.
