# US 11,906,454 B2 · Highly sensitive microcalorimeters for cellular bioenergetics

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- Number: US 11,906,454 B2
- Document ID: US11906454B2
- Status: Granted
- Kind: B2
- Application number: 16/462,059
- Filed: 2017-11-13
- Published: 2019-12-19
- Granted: 2024-02-20
- Earliest claimed: 2016-11-11
- Assignees: President and Fellows of Harvard College
- Applicants: President and Fellows of Harvard College
- Inventors: Jinhye Bae; Joost J Vlassak
- Web page: https://patentgrep.com/patent/US11906454B2

## CPC

- G01N 25/4846: {for a motionless, e.g. solid sample}
- B01L 7/00: Heating or cooling apparatus (autoclaves B01J3/04); Heat insulating devices
- B01L 2300/023: Sending and receiving of information, e.g. using Bluetooth®
- B01L 2300/0663: Whole sensors
- B01L 2300/0848: Specific forms of parts of containers
- B01L 2300/12: Specific details about materials
- B01L 2300/1805: Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
- 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)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE

## Abstract

A microcalorimeter device capable of measuring cellular bioenergetics and systems that are limited in analytic volume. The microcalorimeter device provides sub-nWatt resolution and even tens of pico-Watt resolution, thus enabling resolution of the metabolic rate of a single cell.

## Claims

### Claim 1

A device for quantitatively measuring the metabolic rate of a single cell comprising:
a highly sensitive thermopile-based microcalorimetric sensor further comprising a plurality of individual sensor elements, wherein each individual sensor element comprises a membrane and a combination of at least one heating element and at least one thermopile disposed on the same membrane,
wherein the thermopile is fabricated of a material selected from a combination of a first alloy of Copper and Nickel and a second alloy of Nickel and Chrome, or a combination of the first alloy and a third alloy of Nickel and Chrome, the thermopile-based microcalorimetric sensor provides sub nano-Watt resolution, and the sub nano-Watt resolution measures energy production and consumption in the single cell in real time.

### Claim 2 (depends on 1)

The device of claim 1 wherein the first alloy is approximately 55 percent Copper and approximately 45 percent Nickel by weight, the second alloy approximately 80 percent Nickel and 20 percent Chrome by weight, and the third alloy is approximately 90% nickel and approximately 10% chromium by weight.

### Claim 3 (depends on 2)

The device of claim 2, wherein the first alloy is Constantan, and the second alloy is Nichrome.

### Claim 4 (depends on 1)

The device of claim 1, wherein each individual sensor element includes one centrally positioned sample loading area with a heating element disposed therein, and four separate reference loading areas disposed surrounding the sample loading area, and wherein the sample loading area and reference loading areas are disposed on the same membrane.

### Claim 5 (depends on 1)

The device of claim 1, wherein each individual sensor element includes a single sample loading area and a single reference loading area, wherein the sample loading area and the reference loading area are each provided with heating elements, and wherein the sample loading area and reference loading area are disposed on the same membrane.

### Claim 6 (depends on 1)

The device of claim 1, wherein each individual sensor element includes one centrally positioned reference loading area with four separate sample loading areas disposed surrounding the reference loading area, and wherein the sample loading areas and reference loading area are disposed on the same membrane.

### Claim 7 (depends on 1)

The device of claim 1, wherein the heating elements are configured to enable scanning measurements.

### Claim 8 (depends on 1)

The device of claim 1, wherein the sensor is calibrated by providing a direct link between an input power and a thermopile output.

### Claim 9 (depends on 1)

The device of claim 1, wherein the at least one heating element is serpentine shaped and is disposed within the sample loading area.

### Claim 10 (depends on 1)

The device of claim 1, wherein the thermopile-based microcalorimetric sensor provides tens of pico-Watt resolution.