# US 11,079,718 B2 · Specific malaria detection with digital holographic microscopy

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- Number: US 11,079,718 B2
- Document ID: US11079718B2
- Status: Granted
- Kind: B2
- Application number: 16/651,996
- Filed: 2018-09-25
- Published: 2020-08-20
- Granted: 2021-08-03
- Earliest claimed: 2017-09-29
- Assignees: Siemens Healthcare GmbH
- Applicants: Siemens Healthcare GmbH
- Inventors: Oliver Hayden; Lukas Richter; Matthias Ugele; Gaby Marquardt; Manfred Stanzel
- Web page: https://patentgrep.com/patent/US11079718B2

## CPC

- G03H 1/0443: {Digital holography, i.e. recording holograms with digital recording means (holobject computation G03H1/0866)}
- G01N 15/1434: Optical arrangements
- G01N 15/147: {the analysis being performed on a sample stream}
- G01N 15/1484: {microstructural devices}
- G01N 33/4915: {using flow cells (flow cytometry G01N15/14)}
- G01N 15/14: Optical investigation techniques, e.g. flow cytometry
- G01N 2015/012: {Red blood cells}
- G01N 2015/1006: {for cytology}
- G01N 2015/1454: {using phase shift or interference, e.g. for improving contrast}
- G03H 2001/005: {in microscopy, e.g. digital holographic microscope [DHM]}
- G03H 2001/0471: {Object light being transmitted through the object, e.g. illumination through living cells}
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- G03H: HOLOGRAPHIC PROCESSES OR APPARATUS (holograms, e.g. point holograms, used as ordinary optical elements G02B5/32; producing stereoscopic or other three-dimensional effects G02B30/00; diffraction-grating systems G02B27/44; systems using moiré fringes G02B27/60; optical logic elements G02F3/00; stereo-photography G03B35/00; photosensitive materials or processes for photographic purposes G03C; {stereo-photographic or similar processes G03C9/00}; apparatus for processing exposed photographic materials G03D; analogue computers performing mathematical operations with the aid of optical elements G06E3/00; authentication by radiation, of concealed information carried by holograms or diffraction gratings G06K19/16; holographic storage G11B7/0065, G11C13/04; {stereoscopic or other three dimensional effects in television systems H04N13/00})
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present invention relates to a method of detecting a possible infection of malaria in a patient using a digital optical microscope.

## Claims

### Claim 1

A method of detecting a possible infection of malaria in a patient, comprising:
providing a digital holographic microscope (DHM),
obtaining or providing a sample comprising at least one red blood cell suspected of being affected by malaria obtained from the patient,
mixing the sample comprising the at least one red blood cell with a buffer solution to form the at least one red blood cell into a sphere shape to form a sphere-shaped red blood cell, and introducing the buffer solution comprising the at least one sphere-shaped red blood cell into a microfluidic device, wherein at least one part of a channel of the microfluidic device is comprised in a focal area of the DHM, or introducing the sample comprising the at least one red blood cell into a microfluidic device, and mixing the sample comprising the at least one red blood cell with a buffer solution to form the at least one red blood cell into a sphere shape to form a sphere-shaped red blood cell, wherein at least one part of a channel of the microfluidic device is comprised in a focal area of the DHM,
guiding the at least one sphere-shaped red blood cell into the focal area of the DHM,
detecting the at least one sphere-shaped red blood cell with the DHM, and
determining whether the at least one red blood cell is affected by malaria to determine whether the patient is infected by malaria.

### Claim 2 (depends on 1)

The method of claim 1, wherein the detecting the at least one sphere-shaped red blood cell with the DHM comprises reconstructing the phase and amplitude image obtained by the DHM.

### Claim 3 (depends on 1)

The method of claim 1, wherein a cell volume or cell diameter of the at least one sphere-shaped red blood cell is determined with the DHM to identify a development stage and species of a malaria parasite.

### Claim 4 (depends on 1)

The method of claim 1, wherein at least ⅔ of a volume of the at least one sphere-shaped red blood cell is detected with the DHM.

### Claim 5 (depends on 1)

The method of claim 1, wherein malaria tertiana, malaria tropica, and malaria quartana are differentiated using the DHM.

### Claim 6 (depends on 5)

The method of claim 5, wherein a multitude of red blood cells is detected using the DHM, wherein different stages of malaria species are determined for the multitude of red blood cells.

### Claim 7 (depends on 6)

The method of claim 6, wherein a parasitemia of the multitude of red blood cells is determined comprising determining the ratio of a number of infected cells to a number of total cells.

### Claim 8 (depends on 6)

The method of claim 6, wherein 1*104 to 1*106 red blood cells are detected.

### Claim 9 (depends on 1)

The method of claim 1, wherein the at least one red blood cell is isolated from an original sample of the patient, the original sample comprising the at least one red blood cell.

### Claim 10 (depends on 9)

The method of claim 9, wherein the original sample of the patient comprises a blood sample.
