# US 11,110,488 B1 · Systems and methods to eliminate bubbles using ultrasonic energy

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- Number: US 11,110,488 B1
- Document ID: US11110488B1
- Status: Granted
- Kind: B1
- Application number: 17/308,971
- Filed: 2021-05-05
- Granted: 2021-09-07
- Earliest claimed: 2021-05-05
- Applicants: Rafaela Frota
- Inventors: Rafaela Frota
- Web page: https://patentgrep.com/patent/US11110488B1

## CPC

- B06B 1/0215: {for generating pulses, e.g. bursts of oscillations, envelopes}
- B06B 1/0637: {Spherical array}
- C12M 41/02: {of foam (foam prevention during gasification of liquids B01D19/02)}
- G06T 7/0004: {Industrial image inspection}
- G06T 7/0008: {checking presence/absence}
- G10K 11/346: {using phase variation}
- G10K 15/043: {producing shock waves (G10K15/046, G10K15/06 take precedence; generating seismic energy G01V1/02)}
- B06B 2201/70: Specific application
- G06T 2207/30024: Cell structures in vitro; Tissue sections in vitro
- B06B: METHODS OR APPARATUS FOR GENERATING OR TRANSMITTING MECHANICAL VIBRATIONS OF INFRASONIC, SONIC, OR ULTRASONIC FREQUENCY, {e.g.} FOR PERFORMING MECHANICAL WORK IN GENERAL (for particular applications, see the relevant subclasses, e.g. B07B1/40, B23Q17/12, B24B31/06; measurement of mechanical vibrations G01H; in direction finding, locating, distance or velocity measuring G01S; {generating seismic energy G01V1/02}; control of mechanical vibrations in general G05D; sound-producing devices, e.g. bells, sirens, whistles G10K, {e.g. methods or devices for transmitting, conducting, or directing sound in general G10K11/00}; generation of electrical oscillations H03B; electromechanical resonators in general H03H; electromechanical transducers {for communication techniques, e.g. microphones, speakers} H04R)
- C12M: APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; {APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS}
- G06T: IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
- G10K: SOUND-PRODUCING DEVICES; METHODS OR DEVICES FOR PROTECTING AGAINST, OR FOR DAMPING, NOISE OR OTHER ACOUSTIC WAVES IN GENERAL; ACOUSTICS NOT OTHERWISE PROVIDED FOR

## Abstract

A system to reduce surface bubbles from cell culture media using ultrasonic pulses is disclosed. The system includes a plurality of ultrasonic transducers, a photodetector, a camera, a control circuit, and a cell culture container that includes a cell culture media. The control circuit is communicatively coupled to the plurality of ultrasonic transducers, the temperature sensor, and the camera. The photodetector is used to determine a presence of a surface bubble on the cell culture media. The camera is used to determine a location of the surface bubble when the presence of the surface bubble is determined. The plurality of ultrasonic transducers is used to position an ultrasonic pulse at the location of the surface bubble and thereby reduce the presence of the surface bubble on the cell culture media when the location of the surface bubble is determined.

## Claims

### Claim 1

A system to reduce surface bubbles from cell culture media using ultrasonic pulses, the system comprising:
a plurality of ultrasonic transducers;
a photodetector;
a camera;
a control circuit;
a cell culture container comprising a cell culture media;
wherein the control circuit is communicatively coupled to the plurality of ultrasonic transducers, the temperature sensor, and the camera;
wherein the control circuit is configured to:
determine, via the photodetector, a presence of a surface bubble on the cell culture media;
determine, via the camera, a location of the surface bubble when the presence of the surface bubble is determined;
position, via the plurality of ultrasonic transducers, an ultrasonic pulse at the location of the surface bubble and thereby reduce the presence of the surface bubble on the cell culture media when the location of the surface bubble is determined.

### Claim 2 (depends on 1)

The system of claim 1, wherein to determine the presence of the surface bubble the control circuit is configured to:
illuminate, via a light source communicatively coupled to the control circuit, the cell culture media;
capture, via the photodetector, a spectra reading of the cell culture media;
compare the spectra reading with a base spectra reading of the cell culture media; and
determine the presence of the surface bubble when the spectra reading is greater than the base spectra reading.

### Claim 3 (depends on 2)

The system of claim 2, wherein to determine the location of the surface bubble the control circuit is configured to:
capture, via the camera, an image of the cell culture container when the surface bubble is detected;
convert the image to a raster image;
enhance a contrast of the raster image using a filter to yield a processed image comprising a final pixel count reading;
compare the processed image with a base value pixel count reading of the cell culture media to generate a pixel count reading difference value;
determine a location of the surface bubble when the pixel count reading difference value is greater than a threshold percentage.

### Claim 4 (depends on 3)

The system of claim 3, wherein
the plurality of ultrasonic transducers is arranged as a parametric ultrasonic transducer array that produces a standing wave when activated.

### Claim 5 (depends on 4)

The system of claim 4, wherein
in positioning the ultrasonic pulse, the control circuit is configured to:
activate the parametric ultrasonic transducer array to produce the standing wave; and
position the standing wave on the surface bubble using an ultrasonic beam focusing method.

### Claim 6 (depends on 5)

The system of claim 5, wherein
the surface bubble comprises a bubble resonant frequency;
the standing wave comprises a beam resonant frequency; and
the presence of surface bubble is reduced when the beam resonant frequency matches the bubble resonant frequency.

### Claim 7 (depends on 6)

The system of claim 6, wherein
the plurality of ultrasonic transducers is concavely arranged proximate to the cell culture container.

### Claim 8 (depends on 7)

The system of claim 7, wherein
the light source is oriented orthogonal to the photodetector.

### Claim 9 (depends on 8)

The system of claim 8, further comprising:
a communications device communicatively coupled to the control circuit;
wherein the control circuit is configured to:
transmit, via the communications device, a notification when one or more of the following occur:
the presence of the surface bubble on the culture media is determined; and
the location of the surface bubble is determined.

### Claim 10

A method to reduce surface bubbles from cell culture media, the method comprising:
determining, via a photodetector communicatively coupled to a control circuit, a presence of a surface bubble on a cell culture media, a cell culture container comprising the cell culture media;
determine, via a camera communicatively coupled to the control circuit, a location of the surface bubble when the presence of the surface bubble is determined; and
positioning, via a plurality of ultrasonic transducers communicatively coupled to the control circuit, an ultrasonic pulse at the location of the surface bubble and thereby reduce the presence of the surface bubble on the cell culture media when the location of the surface bubble is determined.

### Claim 11 (depends on 10)

The method of claim 10, wherein determining the presence of the surface bubble comprises:
illuminating, via the control circuit, the cell culture media using a light source;
capturing, via the control circuit, a spectra reading of the cell culture media using the photodetector;
comparing, via the control circuit, the spectra reading with a base spectra reading of the cell culture media; and
determining, via the control circuit, the presence of the surface bubble when the spectra reading is greater than the base spectra reading.

### Claim 12 (depends on 11)

The method of claim 11, wherein determining the location of the surface bubble comprises:
capturing, via the control circuit, an image of the cell culture container using the camera when the surface bubble is detected;
converting, via the control circuit, the image to a raster image;
enhancing, via the control circuit, a contrast of the raster image using a filter to yield a processed image that includes a final pixel count reading;
comparing, via the control circuit, the processed image with a base value pixel count reading of the cell culture media to generate a pixel count reading difference value;
determining, via the control circuit, a location of the surface bubble when the pixel count reading difference value is greater than a threshold percentage.

### Claim 13 (depends on 12)

The method of claim 12, wherein
the plurality of ultrasonic transducers arranged a parametric ultrasonic transducer array that produces a standing wave when activated.

### Claim 14 (depends on 13)

The method of claim 13, wherein positioning the ultrasonic pulse comprises:
activating, via the control circuit, the parametric ultrasonic transducer array to produce the standing wave; and
positioning, via the control circuit, the standing wave on the surface bubble using an ultrasonic beam focusing method.

### Claim 15 (depends on 14)

The method of claim 14, wherein
the surface bubble comprises a bubble resonant frequency;
the single standing wave comprises a beam resonant frequency;
the presence of the surface bubble is reduced when the bubble resonant frequency matches the beam resonant frequency.

### Claim 16 (depends on 15)

The method of claim 15, wherein
the plurality of ultrasonic transducers is concavely arranged and positioned proximate to the cell culture container.

### Claim 17 (depends on 16)

The method of claim 16, wherein
the light source is oriented orthogonal to the photodetector.

### Claim 18 (depends on 17)

The method of claim 17, further comprising:
transmitting, via a communications device communicatively coupled to the control circuit, a notification to a computing device for display on a user interface when one or more of the following occur:
the presence of the surface bubble on the culture media is determined; and
the location of the surface bubble is determined.