Magnetic flow cytometry for individual cell detection

Patent metadata

Field	Value
Publication number	US-9316575-B2
Application number	US-201113820866-A
Country	US
Kind code	B2
Filing date	Aug 29, 2011
Priority date	Sep 8, 2010
Publication date	Apr 19, 2016
Grant date	Apr 19, 2016

Abstract

The disclosure relates to flow cytometry. A method for precise individual cell detection and cell measurement of cells in the flow is disclosed. A pair of magnetoresistive components are used to produce a characteristic measuring signal profile from which the following information can be obtained: number of measurement deviations, measurement deviation distances, measurement deviation amplitudes, measurement deviation direction and measurement deviation direction sequence. The flow speed and the cell diameter can also be determined. Also, the signal noise ratio can be determined using the measurement deviation amplitude.

First claim

What is claimed is:

1. A method for magnetic flow measurement of cells, the method comprising the following steps:
starting up a sensor arrangement, wherein at least a first and a second magnetoresistive component being connected in a Wheatstone bridge in a diagonal arrangement or parallel arrangement, and wherein the first and second magnetoresistive components are arranged with a distance between one another in the direction of flow of the cells, and wherein the distance between the first magnetoresistive component and the second magnetoresistive component is selected based on a type of cell to be detected in the flow of cells,
performing a magnetic marking of the cells,
generating flow of the cells over the sensor arrangement, the flow of the cells firstly being guided via the first and subsequently via the second magnetoresistive component,
detecting individual cells in the flow of the cells, wherein a measurement signal with a characteristic pattern of at least three measurement deviations is produced by the magnetic field of an individual magnetically marked cell that flows over the sensor arrangement, and
evaluating the measurement signal wherein the measurement signal is identified as individual cell detection based on the measurement deviation direction sequence.

2. The method of claim 1 , comprising evaluating at least a further information item from the characteristic measurement signal pattern selected from the group consisting of a measurement deviation number, measurement deviation distances, and measurement deviation amplitudes.

3. The method of claim 1 , wherein the evaluation comprises calculating the flow velocity based on the known distance between the magnetoresistive components.

4. The method of claim 1 , wherein the evaluation comprises calculating a cell diameter based on the measurement deviation distance.

5. The method of claim 1 , wherein the evaluation comprises calculating a signal-to-noise ratio based on the measurement deviation amplitude.

6. The method of claim 1 , wherein superparamagnetic markers are used for the magnetic marking of the cells.

7. The method of claim 1 , wherein the method is performed for magnetic flow measurement of cells of a prescribed type with a characteristic cell diameter, wherein the first and the second magnetoresistive component are arranged at a distance between one another in the flow direction that is at most twice the characteristic cell diameter.

8. The method of claim 1 , wherein:
for the startup of the sensor arrangement four magnetoresistive components are connected to form a first and a second pair in a Wheatstone bridge in a parallel arrangement, and are arranged in series such that a flow of the cells can be guided firstly via the first, subsequently via the second, subsequently via the third, and subsequently via the fourth magnetoresistive component,
wherein the flow of the cells is guided via the four magnetoresistive components in just this sequence, and
wherein the flow velocity is calculated in the evaluation based on the known pair distance between the first and second pair of magnetoresistive components.

9. A device for magnetic flow measurement of magnetically marked cells, comprising:
a flow chamber configured to flow magnetically marked cells therethrough in a direction of flow;
a sensor arrangement, positioned in the flow chamber, comprising at least one Wheatstone bridge with at least a first and a second magnetoresistive component, wherein the magnetoresistive components are connected in a diagonal arrangement or a parallel arrangement, wherein the first and second magnetoresistive components are positioned at least partly transverse to the direction of flow of the magnetically marked cells, and wherein the first and second magnetoresistive components are arranged with a distance between one another in the direction of flow of the magnetically marked cells, and wherein the distance between the first magnetoresistive component and the second magnetoresistive component being selected based on a cell type to be detected in the flow of magnetically marked cells, and wherein the sensor arrangement being configured to detect a measurement signal,
wherein the sensor arrangement is positioned in the flow chamber so that the flow of the magnetically marked cells are firstly guided via the first and subsequently via the second magnetoresistive components,
wherein the distance of the magnetoresistive components has a value such that the magnetic field of an individual magnetically marked cell that flows over the sensor arrangement produces a characteristic measurement signal pattern with at least three measurement deviations, and
evaluation electronics configured to identify the measurement signal as individual cell detection based on the measurement deviation direction sequence.

10. The device of claim 9 , wherein the distance between the magnetoresistive components is at most 50 μm.

11. The device of claim 9 , wherein the evaluation electronics are configured to calculate the flow velocity from the measurement signal pattern based on the known distance between the magnetoresistive components.

12. The device of claim 9 , wherein the evaluation electronics are configured to calculate the cell diameter based on the measurement deviation distance.

13. The device of claim 9 , wherein the evaluation electronics are configured to determine the signal-to-noise ratio based on the measurement deviation amplitude.

14. The device of claim 9 , wherein the sensor arrangement comprises four magnetoresistive components of a Wheatstone bridge, which are connected to form a first and a second pair of magnetoresistive components in a parallel arrangement, and which are arranged in series such that a flow of the cells is guidable firstly via the first, subsequently via the second, subsequently via the third, and subsequently via the fourth magnetoresistive component, and wherein the evaluation electronics are configured to calculate the flow velocity based on the known pair distance between the first and second pair of magnetoresistive components.

15. The device of claim 14 , wherein the pair distance between the first and second pair of magnetoresistive components is greater than the distance between the individual magnetoresistive components within a pair.

Assignees

• Hayden Oliver
• Helou Michael Johannes
• Tedde Sandro Francesco
• Siemens Ag

Inventors

• Hayden Oliver
• Helou Michael Johannes
• Tedde Sandro Francesco

Classifications

• G01N27/72

  by investigating magnetic variables · CPC title

• G01N15/1031 Primary

  by measuring electrical or magnetic effects · CPC title