ISOVOLUMETRIC SPHERING OF RED BLOOD CELLS

Abstract

An automatic analyzer for analyzing a medical probe includes an analysis cell for the probe, a piezo element, and an analysis device. The piezo element can be operated by applying a voltage and a frequency, and in the process an acoustic wave field is generated. A probe located in the analysis cell is located in the acoustic wave field when the piezo element is being operated.

Claims

1. An automatic analyzer for analyzing a medical sample, the analyzer comprising an analysis cell for the sample, a piezo element, and an analysis device, wherein the piezo element can be operated by application of a voltage and a frequency and generates an acoustic wave field, wherein a sample situated in the analysis cell is situated in the acoustic wave field during operation of the piezo element.

2. The automatic analyzer as claimed in claim 1, wherein a sample situated in the analysis cell is heated by the wave field during operation of the piezo element to at least 48 degrees Celsius.

3. The automatic analyzer as claimed in claim 1, wherein the analysis cell is a flow cell.

4. The automatic analyzer as claimed in claim 3, wherein the sample moves within the analysis cell at a flow rate between 0.002 and 5 mm per second.

5. The automatic analyzer as claimed in claim 1, wherein the analysis device comprises an optical microscope for analysis of a sample situated in the analysis cell.

6. The automatic analyzer as claimed in claim 5, wherein the microscope comprises a 20× to 60× objective.

7. The automatic analyzer as claimed in claim 1, wherein a sample is situated in the analysis cell and the sample comprises human or animal cells.

8. A method for sphering a cell of a medical sample comprising: providing the cell situated in an analysis cell; and generating an acoustic wave field using a piezo element operated at a voltage and a frequency wherein the cell is situated in the wave field and is heated and thereby sphered by the wave field.

9. The method as claimed in claim 8, wherein the sphering is done isovolumetrically.

10. The method as claimed in claim 8, wherein the cell is heated to at least 48 degrees Celsius.

11. The method as claimed in claim 8, wherein the analysis cell is a flow cell.

12. The method as claimed in claim 8, further comprising moving the cell within the analysis cell at a flow rate between 0.002 and 5 mm per second.

13. The method as claimed in claim 8, further comprising analyzing or imaging the cell with an analysis device comprising an optical microscope after the sphering, wherein the cell is situated in a focus region of the microscope during the analyzing or imaging.

14. The method as claimed in claim 13, further comprising bringing or holding the cell in the focus region of the microscope by simultaneous use of acoustic and microfluidic forces.

15. The method as claimed in claim 13, wherein the analyzing or imaging the cell occurs within 0.05 to 1 second after the sphering.

16. The method as claimed in claim 8, wherein the cell is a human or animal cell.

17. The method as claimed in claim 13, wherein the cell is a red blood cell and the analyzing of the cell comprises a volume determination or a determination of single-cell hemoglobin (MCH) or a detection of malaria parasites.

18. The method as claimed in claim 8, wherein the cell is heated to at least 50 degrees Celsius.

19. The method as claimed in claim 8 further comprising moving the cell within the analysis cell at a flow rate between 0.002 and 0.1 mm per second.

20. The automatic analyzer as claimed in claim 5, wherein the optical microscope is a digital holographic microscope (DHM).

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0041] The invention will be more particularly elucidated once more by a specific exemplary embodiment with reference to the attached drawings. The example shown is a preferred embodiment of the invention. In the figures:

[0042] FIG. 1 shows an analysis cell (9) in which red blood cells (7) are situated without acoustophoretic heating, wherein a piezo element (1) is operated at 23 volts,

[0043] FIG. 2 shows an analysis cell (9) in which sphered red blood cells (7) are situated with acoustophoretic heating, wherein a piezo element (1) is operated at 75 volts,

[0044] FIG. 3 shows an analysis cell (9) in which red blood cells (7) are situated, wherein a piezo element (1) is operated at 23 volts,

[0045] FIG. 4 shows an analysis cell (9) in which sphered red blood cells (7) are situated, wherein a piezo element (1) is operated at 75 volts.

DETAILED DESCRIPTION OF THE INVENTION

[0046] The analysis cell (9) shown in FIG. 1 comprises channel walls (2) and a piezo element (1) and is part of an automatic analyzer for analyzing cells in a sample. The analyzer comprises an analysis device (10) which is configured as an optical microscope and which comprises a light source for illumination of a sample in the analysis cell (9) and a converging lens for convergence and focusing of light beams proceeding from the illuminated sample. The sample is a blood sample which contains red blood cells (7). The sample is situated in the analysis cell (9), which is configured as a microfluidic flow cell. Furthermore, the microscope comprises a camera comprising a digital recorder, the recorder comprising a CCD chip or a CMOS chip, for recording of the light field imaged in the microscope. The analysis cell (9) and the microscope are configured such that red blood cells (7) situated in an optical window (4) can be imaged and analyzed. The piezo element (1) is arranged in the outer region on the channel wall (2) immediately before the optical window (4) in flow direction x of the red blood cells (7). A velocity profile (8) of the red blood cells (7) moving in direction x within the flow cell is represented as a vector depending on the position of the red blood cells in direction y.

[0047] The piezo element (1) is operated at a voltage of 25 volts and a frequency of about 1 MHz, preferably 1.113 MHz, or at a voltage of 25 volts and a frequency of about 5 MHz, preferably 5.397 MHz. The temperature of the red blood cells (7) is less than 48 degrees Celsius and the red blood cells (7) are present in their native state and are not sphered.

[0048] FIG. 2 shows the same analysis cell (9) as in FIG. 1. Now, the piezo element (1) is operated at a voltage of 75 volts and a frequency of about 1 MHz, preferably 1.113 MHz, or at a voltage of 75 volts and a frequency of about 5 MHz, preferably 5.397 MHz. The temperature of the red blood cells (7) is at least 48 degrees Celsius and the red blood cells (7) are sphered.

[0049] FIG. 3 shows a further analysis cell (9) in which a red blood cell (7) is situated. A velocity profile (8) of the red blood cells (7) moving in direction x within the flow cell is represented as a vector depending on the position of the red blood cells in direction z. A piezo element (1) (not shown) is arranged in the region of the outer side of the channel wall and is operated at a voltage of 23 volts and a frequency of about 1 MHz, preferably 1.113 MHz, or at a voltage of 23 volts and a frequency of about 5 MHz, preferably 5.397 MHz. The temperature of the red blood cells (7) is 36 degrees Celsius and the red blood cell (7) is present in its native state and is not sphered. What is shown is the progression of the acoustic wave (5) generated by the piezo element (1). An acoustic wave node (6) is present in the region of the channel half-height (3) and of the red blood cell (7). Owing to acoustic forces, the red blood cell (7) is drawn into the region of the acoustic wave node and held there.

[0050] FIG. 4 shows the same analysis cell (9) as in FIG. 3. The piezo element (1) is operated at a voltage of 75 volts and a frequency of about 1 MHz, preferably 1.113 MHz, or at a voltage of 75 volts and a frequency of about 5 MHz, preferably 5.397 MHz. The temperature of the red blood cell (7) is 48 degrees Celsius and the red blood cell (7) is completely sphered. What is shown is the progression of the acoustic wave (5) generated by the piezo element (1). An acoustic wave node (6) is present in the region of the channel half-height (3) and of the red blood cell (7). Owing to acoustic forces, the red blood cell (7) is drawn into the region of the acoustic wave node and held there.

LIST OF REFERENCE SIGNS

[0051] 1 Piezo element [0052] 2 Channel wall [0053] 3 Channel half-width [0054] 4 Optical window [0055] 5 Acoustic wave [0056] 6 Acoustic wave node [0057] 7 Red blood cell (RBC) [0058] 8 Velocity profile [0059] 9 Analysis cell