# US 11,442,010 B2 · Measuring system, such as an interaction measuring system and a measuring method

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- Number: US 11,442,010 B2
- Document ID: US11442010B2
- Status: Granted
- Kind: B2
- Application number: 16/701,866
- Filed: 2019-12-03
- Published: 2020-04-02
- Granted: 2022-09-13
- Earliest claimed: 2019-12-03
- Assignees: Ibis Technologies B.V.
- Applicants: Ibis Technologies B.V.
- Inventors: Richard Bernardus Maria Schasfoort
- Web page: https://patentgrep.com/patent/US11442010B2

## CPC

- G01N 21/553: {and using surface plasmons (fluorescence excitation G01N21/648; enhanced Raman G01N21/658)}
- B01L 3/502715: {characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces}
- B01L 3/502738: {characterised by integrated valves (throttle valves in microfluidic sample containers B01L3/502746)}
- G01N 21/05: Flow-through cuvettes (G01N21/09 takes precedence; handling fluid samples G01N1/10)
- G01N 35/08: using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
- G01N 35/1095: {for supplying the samples to flow-through analysers (for a specific analyser see relevant groups, e.g. under G01N15/00, G01N21/00, G01N27/00, G01N30/00, H01J49/00)}
- B01L 3/502784: {specially adapted for droplet or plug flow, e.g. digital microfluidics}
- B01L 2300/0663: Whole sensors
- B01L 2300/0877: Flow chambers
- 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)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE

## Abstract

The present invention relates to a method for the measurement of at least one sample by the interaction with the surface in the field of at least one sensor surface, such as surface plasmon resonance measurement, comprising the steps of: i) sampling the sample and a buffer; ii) transporting the sample and the buffer to at least one flow cell which is in liquid contact with the sensor surface of at least one sensor for measuring a parameter of a sample by interaction of the sample at the sensor surface in the field of the sensor surface; iii) transporting the sample into the flow cell into contact with the sensor surface; iv) handling a separation fluidum by inserting and/or removing the separation fluidum by between the sample and the buffer upstream and/or downstream of the sensor surface; v) measuring the interaction of the sample at the sensor surface; and vi) dispensing the sample from the flow cell, and to a measuring system for such method.

## Claims

### Claim 1

A system for measurement of at least one sample, comprising:
at least one sensor having at least one sensor surface;
at least one flow cell which is in liquid contact with the at least one sensor surface,
wherein the at least one flow cell comprises:
a flow cell inlet connected to an inlet port of an upstream part of the flow cell; and
a flow cell outlet connected to an outlet port of a downstream part of the flow cell;
sampling means connected via first tubing to the flow cell inlet, wherein the sampling means is configured to supply at least one sample and separation fluid to the first tubing filled with a buffer such that the at least one sample is separated from the buffer by the separation fluid;
handling means configured to handle the separation fluid upstream of the at least one sensor surface of the at least one sensor, wherein the handling means comprises an inlet parking line connected at a first connection to the first tubing between the sampling means and the flow cell inlet for handling the separation fluid upstream of the at least one sensor surface; and
transport means connected via second tubing to the flow cell outlet,
wherein the transport means is connected to the flow cell inlet via the inlet parking line,
wherein the transport means is configured to transport the at least one sample, the separation fluid, or the buffer through the first tubing, the second tubing, and the at least one flow cell, and
wherein the handling means is configured to remove the separation fluid from in between the at least one sample and the buffer from the first tubing in the upstream part of the flow cell.

### Claim 2 (depends on 1)

The system according to claim 1,
wherein the handling means further comprises an outlet parking line connected at a second connection to the second tubing between the flow cell outlet and the transport means,
wherein the outlet parking line is configured to handle the separation fluid downstream of the at least one sensor surface, and
wherein the handling means is further configured to:
handle the separation fluid upstream of the at least one sensor surface;
handle the separation fluid downstream of the at least one sensor surface; and
insert the separation fluid in between the at least one sample and the buffer in the second tubing in the downstream part of the flow cell.

### Claim 3 (depends on 2)

The system according to claim 2, wherein the handling means is further configured to remove the separation fluid from in between the at least one sample and the buffer from the second tubing in the downstream part of the flow cell.

### Claim 4 (depends on 1)

The system according to claim 1, wherein the transport means is configured for a back and forth movement of liquids, and wherein a distance of the second connection to the outlet port of the flow cell is such that, during the back and forth movement, the separation fluid will not contact the at least one sensor surface.

### Claim 5 (depends on 4)

The system according to claim 4, wherein the distance is such that a volume between the second connection and the outlet port is greater than:
a volume of the separation fluid between the at least one sample and the buffer; and
a stroke volume of a back-and-forth stroke.

### Claim 6 (depends on 5)

The system according to claim 5, wherein a sample volume is larger than a liquid volume between the first connection and the second connection.

### Claim 7 (depends on 1)

The system according to claim 1, further comprising
at least one sample parking line connected to
the inlet parking line.

### Claim 8 (depends on 1)

The system according to claim 1, further comprising a detection unit configured to measure at least one parameter of the at least one sample caused by interaction of the at least one sample at the at least one sensor surface in a field of the at least one sensor surface, wherein the system is a surface plasmon resonance measuring system, and wherein the detection unit is an optical unit for measuring a surface plasmon resonance angle of light incidence at the at least one sensor surface.

### Claim 9 (depends on 1)

The system according to claim 1, wherein the at least one sensor surface comprises binding ligands which selectively capture a target compound.

### Claim 10 (depends on 1)

The system according to claim 1, wherein removing the separation fluid from in between the at least one sample and the buffer from the first tubing upstream of the flow cell comprises taking up some of the buffer, the separation fluid, and some of the at least one sample.

### Claim 11 (depends on 2)

The system according to claim 2, wherein inserting the separation fluid in between the at least one sample and the buffer into the second tubing downstream of the flow cell comprises tuning to a front of the at least one sample by pinching off a mixing/diffusion region of an interface between the at least one sample and the buffer.
