# US 2019/0170672 A1 · System and Method for Characterizing Bioreactor Fluids

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- Number: US 2019/0170672 A1
- Document ID: US20190170672A1
- Status: Published application
- Kind: A1
- Application number: 16/205,820
- Filed: 2018-11-30
- Published: 2019-06-06
- Earliest claimed: 2017-12-01
- Assignees: DEKA Products Limited Partnership
- Applicants: DEKA Products Limited Partnership
- Inventors: David Blumberg, JR.; Michael C. Tilley; Derek G. Kane; David C. Nivens
- Web page: https://patentgrep.com/patent/US20190170672A1

## CPC

- G01N 24/088: {Assessment or manipulation of a chemical or biochemical reaction, e.g. verification whether a chemical reaction occurred or whether a ligand binds to a receptor in drug screening or assessing reaction kinetics}
- C12M 47/04: {Cell isolation or sorting (purging biological preparations of unwanted cells C12N5/0081, determining the presence or kind of microorganism C12Q1/04)}
- G01R 33/307: {specially adapted for moving the sample relative to the MR system, e.g. spinning mechanisms, flow cells or means for positioning the sample inside a spectrometer}
- G01R 33/383: using permanent magnets
- G01R 33/3873: using ferromagnetic bodies {; Passive shimming}
- G01R 33/445: {MR involving a non-standard magnetic field B0, e.g. of low magnitude as in the earth's magnetic field or in nanoTesla spectroscopy, comprising a polarizing magnetic field for pre-polarisation, B0 with a temporal variation of its magnitude or direction such as field cycling of B0 or rotation of the direction of B0, or spatially inhomogeneous B0 like in fringe-field MR or in stray-field imaging}
- G01R 33/465: applied to biological material, e.g. in vitro testing
- H01F 7/0226: {PM with variable field strength (H01F7/0284 takes precedence)}
- G01N 24/085: {Analysis of materials for the purpose of controlling industrial production systems}
- 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)
- 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}
- G01R: MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES (indicating correct tuning of resonant circuits H03J3/12)
- H01F: MAGNETS; INDUCTANCES; TRANSFORMERS; SELECTION OF MATERIALS FOR THEIR MAGNETIC PROPERTIES

## Abstract

A magnetic resonance device for monitoring growth of tissue in one or more bioreactors. The device can include a first magnet and a second magnet that can form a uniform magnetic field of desired strength around at least one sample of effluent from at least one bioreactor. At the command of a controller, an RF signal can illuminate the at least one magnetized sample, and sensors can detect at least one echo signal from the at least one magnetized sample. The controller can characterize the at least one sample based on the at least one echo signal. A resonator can shape the at least one echo signal.

## Claims

### Claim 1

A method for characterizing at least one sample from at least one bioreactor using a magnetic resonance apparatus, the magnetic resonance apparatus having a first magnet and a second magnet, the first magnet and the second magnet positioned to set up a magnetic field, the method comprising:
determining a desired magnetic field strength for the magnetic field;
rotating the first magnet and positioning the second magnet to achieve the desired magnetic field strength;
circulating the at least one sample in the magnetic field;
periodically illuminating the at least one sample with an electronic signal;
sensing at least one echo signal between the illuminations; and
characterizing the at least one sample based on the sensed least one echo signal.

### Claim 2 (depends on 1)

The method as in claim 1 further comprising:
rotating the first magnet to achieve a changed magnetic field strength and a changed magnetic field;
circulating the at least one sample in the changed magnetic field;
periodically illuminating the at least one sample with the electronic signal;
sensing a second at least one echo signal between the illuminations; and
characterizing the at least one sample based at least on a comparison between the second at least one echo signal and the sensed least one echo signal.

### Claim 3 (depends on 2)

The method as in claim 2 wherein the characterizing comprises envelope detection and curve fit.

### Claim 4

An apparatus for identifying contents of effluent from at least one tissue bioreactor comprising:
a rotatable magnet;
at least one container including the effluent, the at least one container positioned in proximity to the rotatable magnet;
a second magnet positioned in proximity to the at least one container, the second magnet positioned to form a magnetic field across the effluent, magnetizing the effluent;
an adjustment means rotating the rotatable magnet to adjust the strength of the magnetic field;
a transmitter periodically transmitting at least one non-ionizing signal across the magnetized effluent, the at least one non-ionizing signal energizing the magnetized effluent;
a receiver receiving at least one echo signal from the magnetized energized effluent based on the at least one non-ionizing signal; and
a controller controlling the transmitter, the receiver, and the adjustment means by means of commands, the controller characterizing the at least one echo signal, the controller identifying the contents of the effluent based on the characterized at least one echo signal.

### Claim 5 (depends on 4)

The apparatus as in claim 4 further comprising:
a spreader operably positioned between the rotatable magnet and the second magnet, the spreader enabling uniformity of the magnetic field.

### Claim 6 (depends on 5)

The apparatus as in claim 5 wherein the rotatable magnet comprises a diametric magnetization vector, the diametric magnetization vector being substantially perpendicular to the spreader.

### Claim 7 (depends on 4)

The apparatus as in claim 4 further comprising:
a resonator shaping the transmitted at least one non-ionizing signal.

### Claim 8 (depends on 4)

The apparatus as in claim 4 further comprising:
a resonator shaping the received at least one echo signal.

### Claim 9 (depends on 4)

The apparatus as in claim 4 further comprising:
a positioner adjusting the strength of the magnetic field based on a position of the second magnet.

### Claim 10 (depends on 9)

The apparatus as in claim 9 wherein the positioner responds to the commands from the controller.

### Claim 11 (depends on 4)

The apparatus as in claim 4 further comprising an electronic signal generator, the generator supplying the at least one non-ionizing signal, the generator responding to the commands from the controller.

### Claim 12 (depends on 11)

The apparatus as in claim 11 further comprising:
a temperature sensor providing temperature data to the controller, the controller commanding the transmitter to adjust, based on the temperature data, a center frequency of the electronic signal to accommodate magnetic drift.

### Claim 13

A method for characterizing at least one sample from at least one bioreactor using a magnetic resonance apparatus, the magnetic resonance apparatus having a first magnet and a second magnet, the first magnet and the second magnet positioned a pre-selected distance from one another to set up a magnetic field, the first magnet and the second magnet positioned within an enclosure forming a path for the magnetic field, the method comprising:
positioning a first slug between the first magnet and the enclosure, the first slug including magnetic material;
positioning a second slug between the second magnet and the enclosure, the second slug including magnetic material;
shaping the uniformity of the magnetic field using variable reluctance, to create a uniform magnetic field, by adjusting the positions of the first slug and the second slug;
circulating the at least one sample in the uniform magnetic field, the at least one sample being associated with at least one coil;
periodically illuminating the at least one sample and the at least one coil with an electronic signal;
sensing at least one echo signal between the illuminations; and
characterizing the at least one sample based on the sensed least one echo signal.

### Claim 14 (depends on 13)

The method as in claim 13 further comprising:
directing the electronic signal using a resonator.

### Claim 15 (depends on 13)

The method as in claim 13 wherein the pre-selected distance between the first magnet and the second magnet comprises about 0.3 inches.

### Claim 16 (depends on 13)

The method as in claim 13 wherein the first slug and the second slug are surrounded by a non-stick material.

### Claim 17 (depends on 13)

The method as in claim 13 further comprising:
controlling the circulating, illuminating, sensing, and characterizing with an automatic controller.

### Claim 18

A system method for characterizing at least one sample from at least one bioreactor comprising:
an enclosure forming a path for a magnetic field, the enclosure including a plurality of cavities accommodating a first magnet, a second magnet, a first positioning means, a second positioning means, a first slug, and a second slug, the first magnet and the second magnet positioned a pre-selected distance from one another within two of the cavities, the first slug positioned between the first magnet and the enclosure, the first slug including magnetic material, the second slug positioned between the second magnet and the enclosure, the second slug including magnetic material; and
a controller controlling the first positioning means and the second positioning means to position the first slug and the second slug to shape the uniformity of the magnetic field using variable reluctance to create a uniform magnetic field, the controller enabling circulation of the at least one sample in the magnetic field, the at least one sample being associated with at least one coil, the controller periodically illuminating the at least one sample and the at least one coil with an RF signal, the controller sensing at least one echo signal between the illuminations, and the controller characterizing the at least one sample based on the sensed least one echo signal.

### Claim 19 (depends on 18)

The system as in claim 18 further comprising:
a sample tube encircled by the at least one coil, the sample tube resting between the first magnet and the second magnet, the sample tube providing a channel for the at least one sample.

### Claim 20 (depends on 18)

The system as in claim 18 further comprising:
a resonator shaping the at least one echo signal.
