CN113465789A - Open micro-nano calorimeter system for cell metabolism heat detection - Google Patents
Open micro-nano calorimeter system for cell metabolism heat detection Download PDFInfo
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- CN113465789A CN113465789A CN202110746385.6A CN202110746385A CN113465789A CN 113465789 A CN113465789 A CN 113465789A CN 202110746385 A CN202110746385 A CN 202110746385A CN 113465789 A CN113465789 A CN 113465789A
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01K—MEASURING TEMPERATURE; MEASURING QUANTITY OF HEAT; THERMALLY-SENSITIVE ELEMENTS NOT OTHERWISE PROVIDED FOR
- G01K17/00—Measuring quantity of heat
- G01K17/006—Microcalorimeters, e.g. using silicon microstructures
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N25/00—Investigating or analyzing materials by the use of thermal means
- G01N25/20—Investigating or analyzing materials by the use of thermal means by investigating the development of heat, i.e. calorimetry, e.g. by measuring specific heat, by measuring thermal conductivity
Abstract
An open micro-nano calorimeter system for detecting cell metabolism heat comprises a thermopile sensor, a sample titration instrument, a PCB (printed circuit board), a digital source meter and a computer; the inner cavity of the thermopile sensor is used as a sample reaction chamber, a silicon substrate is arranged below the sample reaction chamber, a thin film is arranged at the upper part of the silicon substrate, the center of the thin film is used for bearing a sample, a plurality of thermopiles are uniformly distributed on the thin film on the circumference of the sample, and the thermopiles are in communication connection with a computer through a PCB (printed circuit board) and a digital source meter in sequence; a sample feeding port is arranged on a shell of the thermopile sensor above the sample reaction chamber, a glass plate is covered above the sample feeding port, a sample feeding hole is arranged in the center of the glass plate, and the sample feeding hole is sealed by glycerol; the sample titration instrument conveys a sample to the film through the sample conveying hole; the PCB circuit board is an amplifying circuit; the digital source meter is in communication connection with the PCB through a BNC connector; the computer is in communication connection with the digital source meter through a GPIB-USB-HS data line; the sample reaction chamber is directly contacted with air through a sample feeding port of the shell of the thermopile sensor.
Description
Technical Field
The invention belongs to the technical field of calorimeters, and particularly relates to an open micro-nano calorimeter system for detecting cell metabolic heat.
Background
In the past decades, traditional large-scale calorimeters have been successfully miniaturized through a nano manufacturing technology to form a micro-nano calorimeter with high response speed and high resolution, and an important application of the micro-nano calorimeter is to perform non-invasive characterization on a metabolic process of cells or microorganisms so as to reveal an unknown mechanism or activity of cell metabolism.
The existing micro-nano calorimeter can be divided into two types in structure, wherein one type is a closed micro-nano calorimeter, and the other type is an open micro-nano calorimeter. For a closed micro-nano calorimeter, a closed fluid chamber is used for conveying a sample, and in order to obtain higher sensitivity, vacuum is sometimes introduced into a calorimeter system, which means that the calorimeter system needs a highly complex structure, and the popularization and application of the closed calorimeter system are limited. For an open micro-nano calorimeter, the sample can be conveyed under the condition of not contacting a fluid chamber, and the open micro-nano calorimeter has the advantages of simple structure and easiness in liquid treatment, but has the defect of lower volumetric specific heat power resolution.
Although performance attributes such as sensitivity, signal-to-noise ratio, volumetric specific heat power resolution, etc. are closely related to the choice of sample volume, optimization of the sample volume is quite difficult. When the sample volume is small, although higher sensitivity can be obtained, its volumetric specific heat power resolution is reduced and the signal-to-noise ratio is also reduced. When the sample volume is large, signal degradation results. Thus, the performance improvement due to the change in sample volume is always offset by other factors.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides an open micro-nano calorimeter system for cell metabolic heat detection, which can meet the optimization of sample volume, not only can provide enough signal-to-noise ratio in the cell metabolic heat detection process, but also can meet the performance requirements of sensitivity and volume specific heat power resolution, and effectively improves the comprehensive performance of the open micro-nano calorimeter system.
In order to achieve the purpose, the invention adopts the following technical scheme: an open micro-nano calorimeter system for detecting cell metabolism heat comprises a thermopile sensor, a sample titration instrument, a PCB (printed circuit board), a digital source meter and a computer; the inner cavity of the thermopile sensor is used as a sample reaction chamber, a silicon substrate is arranged below the sample reaction chamber, a thin film is arranged on the upper part of the silicon substrate, the center of the thin film is used for bearing a sample, a plurality of thermopiles are uniformly distributed on the thin film in the circumferential direction of the sample, and the thermopiles are in communication connection with a computer sequentially through a PCB (printed circuit board) and a digital source meter; a sample feeding port is formed in the shell of the thermopile sensor above the sample reaction chamber, a glass plate covers the sample feeding port, and a sample feeding hole is formed in the center of the glass plate; the sample titration instrument delivers a sample to the membrane through the sample delivery aperture.
The PCB is an amplifying circuit and is used for receiving and amplifying voltage signals output by the thermopile sensor.
The digital source meter is in communication connection with the PCB through the BNC connector, and voltage signals output by the PCB are detected through the digital source meter.
The computer is in communication connection with the digital source meter through a GPIB-USB-HS data line, and the collected signal data are recorded through the computer.
When the sample titration instrument delivers the sample to the film through the sample delivery hole, the sample delivery hole is sealed by glycerol for thermal protection of the sample.
The sample reaction chamber is in direct contact with air through a sample feeding port on the shell of the thermopile sensor.
The invention has the beneficial effects that:
the open micro-nano calorimeter system for detecting the cell metabolic heat can meet the optimization of the sample volume, not only can provide enough signal-to-noise ratio in the cell metabolic heat detection process, but also can meet the performance requirements of sensitivity and volume specific heat power resolution, and effectively improves the comprehensive performance of the open micro-nano calorimeter system.
Drawings
FIG. 1 is a schematic diagram of the structure of an open micro-nano calorimeter system for detecting the heat of metabolism of cells according to the present invention;
FIG. 2 is a temperature change curve of a sample at different volumes under constant power based on a numerical model in the example;
FIG. 3 is a graph showing the thermal conductivity and thermal power sensitivity of samples of different volumes based on numerical models in the examples;
FIG. 4 is a signal-to-noise ratio curve of samples of different volumes based on numerical model in the example;
FIG. 5 is a graph showing the thermal power resolution and the volumetric specific thermal power resolution of samples at different volumes based on a numerical model in the example;
in the figure, 1-thermopile sensor, 2-sample titration instrument, 3-PCB circuit board, 4-digital source meter, 5-computer, 6-sample reaction chamber, 7-silicon substrate, 8-thin film, 9-sample, 10-thermopile, 11-glass plate, 12-sample feeding hole, 13-sample feeding port.
Detailed Description
The invention is described in further detail below with reference to the figures and the specific embodiments.
As shown in fig. 1, an open micro-nano calorimeter system for detecting cell metabolic heat comprises a thermopile sensor 1, a sample titration instrument 2, a PCB 3, a digital source meter 4 and a computer 5; the inner cavity of the thermopile sensor 1 serves as a sample reaction chamber 6, a silicon substrate 7 is arranged below the sample reaction chamber 6, a thin film 8 is arranged on the upper portion of the silicon substrate 7, the center of the thin film 8 is used for bearing a sample 9, a plurality of thermopiles 10 are uniformly distributed on the thin film 8 in the circumferential direction of the sample 9, and the thermopiles 10 are in communication connection with a computer 5 sequentially through a PCB 3 and a digital source meter 4; a sample feeding port 13 is formed in the shell of the thermopile sensor 1 above the sample reaction chamber 6, a glass plate 11 covers the sample feeding port 13, and a sample feeding hole 12 is formed in the center of the glass plate 11; the sample titration apparatus 2 delivers a sample 9 through a sample delivery aperture 12 onto a membrane 8.
In this embodiment, the thermopile sensor 1 is formed by transforming a commercial infrared sensor with a model number of S-25/Dexter Research, 20 Bi/SB thermopiles 10 are uniformly distributed on the film 8, and the temperature response is 3600 μ V/K, which is used for converting a thermal signal generated by the sample 9 into a voltage signal. Further, the width of the sample reaction chamber 6 was 2mm, and the depth of the sample reaction chamber 6 was 0.5 mm.
The PCB circuit board 3 is an amplifying circuit and is used for receiving and amplifying voltage signals output by the thermopile sensor 1. In this embodiment, the PCB 3 employs a zero drift dc chopper amplifier with a model number of AD8628, the gain is 1000 times, and the cutoff frequency is 1 Hz.
The digital source meter 4 is in communication connection with the PCB 3 through a BNC connector, and detects a voltage signal output by the PCB 3 through the digital source meter 4. In this embodiment, the digital source table 4 is Keithley 2400.
The computer 5 is in communication connection with the digital source meter 4 through a GPIB-USB-HS data line, and the collected signal data are recorded through the computer 5. In this embodiment, a LabVIEW program is embedded in the computer 5, and the voltage signal is recorded by the LabVIEW program.
After the sample titration apparatus 2 delivers the sample 9 to the membrane 8 through the sample delivery port 12, the sample delivery port 12 is sealed with glycerol for thermal protection of the sample 9.
The sample reaction chamber 6 is in direct contact with air through a sample feed port in the housing of the thermopile sensor 1.
The one-time use process of the present invention is described below with reference to the accompanying drawings:
in order to reveal the performance parameter information of the open micro-nano calorimeter system in the process of detecting the slow change of the thermal power of the cell metabolic heat, a numerical model of the micro-nano calorimeter can be established by using Comsol 5.4 software, and a thermal power step signal of 1 muW is specifically applied to the established micro-nano calorimeter counting value model, so that the corresponding thermal response can be obtained. Specifically, as shown in fig. 2, the temperature variation curve of the sample at different volumes under constant power is shown. According to the thermal response result, the relationship between each performance parameter and the volume of the micro-nano calorimeter can be further obtained, and finally the performance parameter information of the micro-nano calorimeter counting value model established at this time can be obtained. Specifically, as shown in fig. 3, the thermal conductance and thermal power sensitivity curves of the sample at different volumes are shown. As shown in fig. 4, the signal-to-noise ratio variation curves of the samples at different volumes are shown. As shown in FIG. 5, the thermal power resolution and the volumetric specific thermal power resolution of the sample are plotted against the volume.
According to the simulation result aiming at the micro-nano calorimetric counting value model, the signal-to-noise ratio and the thermal power resolution ratio are reduced along with the reduction of the sample volume, but the sensitivity and the volumetric thermal power resolution ratio are gradually improved, so that the sample volume can be reasonably optimized according to the simulation result to achieve the balance of various performance parameters, and the comprehensive performance of the open micro-nano calorimeter system is further improved.
Sample 9 was analyzed for tetrahymena pyriformis as an example. When the sample volume is 50nL, the signal-to-noise ratio is 1, the volumetric specific heat power is 3.58mW/L, the thermal power resolution is 0.18nW, the sensitivity is 48.98V/W, and the time constant is 1.78 s. When the sample volume is 240nL, the signal-to-noise ratio is 3, the volumetric specific heat power is 1.1mW/L, the thermal power resolution is 0.25nW, the sensitivity is 34V/W, and the time constant is 4.8 s.
It was found that at a sample volume of 50nL, no signal was observed at a signal-to-noise ratio of 1, and that the metabolic heat produced by Tetrahymena pyriformis could not be effectively detected at a thermal power resolution of 0.18 nW. When the optimum combination of performance parameters was achieved at the expense of some sensitivity and time constants, i.e., by balancing the performance parameters, it was found that the signal-to-noise ratio could reach 3 even at a sample volume of 240nL and that 0.792nW of metabolic heat generated by Tetrahymena pyriformis was sufficient to detect at a thermal power resolution of 0.25 nW.
Therefore, it can be seen from the above examples that the open micro-nano calorimeter system of the present invention has good applicability in the detection of the heat of metabolism of cells.
The embodiments are not intended to limit the scope of the present invention, and all equivalent implementations or modifications without departing from the scope of the present invention are intended to be included in the scope of the present invention.
Claims (6)
1. An open micro-nano calorimeter system for the detection of the heat of metabolism of cells, characterized in that: the device comprises a thermopile sensor, a sample titration instrument, a PCB (printed Circuit Board), a digital source meter and a computer; the inner cavity of the thermopile sensor is used as a sample reaction chamber, a silicon substrate is arranged below the sample reaction chamber, a thin film is arranged on the upper part of the silicon substrate, the center of the thin film is used for bearing a sample, a plurality of thermopiles are uniformly distributed on the thin film in the circumferential direction of the sample, and the thermopiles are in communication connection with a computer sequentially through a PCB (printed circuit board) and a digital source meter; a sample feeding port is formed in the shell of the thermopile sensor above the sample reaction chamber, a glass plate covers the sample feeding port, and a sample feeding hole is formed in the center of the glass plate; the sample titration instrument delivers a sample to the membrane through the sample delivery aperture.
2. An open micro-nano calorimeter system for the detection of heat of metabolism of cells, according to claim 1, wherein: the PCB is an amplifying circuit and is used for receiving and amplifying voltage signals output by the thermopile sensor.
3. An open micro-nano calorimeter system for the detection of heat of metabolism of cells, according to claim 1, wherein: the digital source meter is in communication connection with the PCB through the BNC connector, and voltage signals output by the PCB are detected through the digital source meter.
4. An open micro-nano calorimeter system for the detection of heat of metabolism of cells, according to claim 1, wherein: the computer is in communication connection with the digital source meter through a GPIB-USB-HS data line, and the collected signal data are recorded through the computer.
5. An open micro-nano calorimeter system for the detection of heat of metabolism of cells, according to claim 1, wherein: when the sample titration instrument delivers the sample to the film through the sample delivery hole, the sample delivery hole is sealed by glycerol for thermal protection of the sample.
6. An open micro-nano calorimeter system for the detection of heat of metabolism of cells, according to claim 1, wherein: the sample reaction chamber is in direct contact with air through a sample feeding port on the shell of the thermopile sensor.
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