CN-115468684-B - Microcalorimeter chip based on flexible printed circuit technology and preparation method thereof

CN115468684BCN 115468684 BCN115468684 BCN 115468684BCN-115468684-B

Abstract

The invention discloses a microcalorimeter chip based on a flexible printed circuit process and a preparation method thereof. The microcalorimeter chip comprises a substrate, a virtual reaction cavity and a temperature sensitive unit, wherein the virtual reaction cavity is arranged in a central detection area of the substrate and is used for wrapping a sample, the virtual reaction cavity is formed by adding mineral oil to the surface of the substrate subjected to oleophobic treatment, and the temperature sensitive unit is arranged at the bottom of the substrate and is used for detecting the temperature of the sample in the reaction process. According to the invention, mineral oil is added to the surface of the substrate subjected to oleophobic treatment to form a virtual reaction cavity, and the sample is packaged by using vacuum oil with low saturated vapor pressure, so that the evaporation of the sample in a vacuum environment can be prevented, and the processing technology of a microfluidic channel is simplified by the open reaction cavity.

Inventors

ZHU HANLIANG
WANG LAN
Pavel Noitzl

Assignees

西北工业大学
西北工业大学

Dates

Publication Date: 20260421
Application Date: 20220830
Priority Date: 20220830

Claims (5)

1. A microcalorimeter chip based on a flexible printed circuit process is characterized by comprising a substrate, a virtual reaction cavity and a plurality of temperature sensitive units, wherein the substrate is made of a flexible polyimide film and is prepared by adopting the flexible printed circuit process, the virtual reaction cavity is arranged in a central detection area of the substrate and is used for wrapping a sample, the virtual reaction cavity is formed by adding mineral oil into the central detection area of the substrate subjected to oleophobic treatment, the temperature sensitive units are arranged at the bottom of the central detection area of the substrate and are used for detecting the temperature of the sample in the reaction process, and the temperature sensitive units adopt standardized Pt1000 thermal resistors or semiconductor thermal resistors; Firstly, adding mineral oil to the surface of a substrate subjected to oleophobic treatment for wrapping sample liquid drops, and then injecting the sample into the oil drops by using a nanoliter injector to form a stable 'water-in-oil' virtual reaction cavity; when tested in a vacuum environment, the samples were encapsulated with vacuum oil having a low saturated vapor pressure; the substrate is of a hollowed-out structure.
2. The micro calorimeter chip based on the flexible printed circuit process according to claim 1, wherein the preparation method of the micro calorimeter chip based on the flexible printed circuit process comprises the following steps: Preparing a flexible polyimide substrate; welding a plurality of temperature sensitive units with the same nominal resistance value to corresponding positions of a substrate through a surface mounting technology; Mineral oil is added to the central detection zone of the substrate to form a virtual reaction chamber.
3. The microcalorimeter chip based on the flexible printed circuit process according to claim 2, wherein said preparing a flexible polyimide substrate comprises: forming a required circuit pattern on the copper foil plate by adopting an etching process to obtain a patterned copper foil plate; Placing the patterned copper foil plate and the polyimide film into a pressing machine for hot-press bonding to obtain a flexible circuit board; Machining the flexible circuit board according to the design pattern by using a numerical control machine tool; And electroplating a nickel layer on the surface of the copper foil, and then electroplating a gold layer at a required position to serve as a bonding pad by using dry film photoetching as a barrier layer.
4. A microcalorimeter chip according to claim 3 based on the flexible printed circuit process, wherein the desired circuit pattern is formed on the copper foil plate by etching process to obtain a patterned copper foil plate, comprising: and pasting a dry film on the copper foil board by a hot pressing method, exposing under ultraviolet light to transfer the pattern on the mask plate onto the dry film, then developing to remove unnecessary non-structural parts, etching unnecessary copper in copper etching liquid by using the dry film as a barrier layer to form a necessary circuit pattern, and removing the residual dry film to obtain the patterned copper foil board.
5. The microcalorimeter chip according to claim 2, further comprising, prior to adding mineral oil to said substrate surface to form a virtual reaction chamber: and (3) carrying out hydrophobic and oleophobic treatment on the surface of the substrate, and forming an additional perfluoro decyl triethoxysilane monomolecular layer on the surface of the substrate by adopting a chemical vapor deposition method, so that the contact angles of water and oil on the surface of the substrate reach 99.4 degrees and 55.2 degrees respectively.

Description

Microcalorimeter chip based on flexible printed circuit technology and preparation method thereof Technical Field The invention relates to the technical field of microcalorimeter chips, in particular to a microcalorimeter chip based on a flexible printed circuit process and a preparation method thereof. Background Many physical changes, chemical reactions and biological processes are associated with the generation or absorption of heat, so calorimetry is a powerful tool to study these reaction processes and to be able to directly detect the change in heat in the process. Later-developed microcalorimetry is a powerful tool for the study of biological thermodynamics and biological kinetics. The method is a label-free non-invasive detection scheme, and can directly monitor the metabolism of living cells and the heat change in the interaction process between biomacromolecules in real time. The micro-thermal techniques currently available for thermal analysis of fluid samples fall into two main categories, namely conventional micro-thermal instruments and micro-calorimeter chip systems manufactured based on microelectromechanical systems (microelectromechanical system, MEMS) technology. Conventional micro-thermal instruments typically use large-volume aluminum crucibles or hundreds of microliters of specialty containers to package the sample, which is large in sample usage, slow in thermal response time, and low in temperature resolution. While micro calorimeter chips manufactured based on MEMS technology can conduct rapid high-resolution thermal analysis research on micro liquid samples, their complex and expensive chip manufacturing process makes this technology still in laboratory research stage. In order to meet the requirement of real-time monitoring of heat balance in biochemical reaction process, especially high-precision measurement of single-cell metabolic heat and micro chemical reaction enthalpy change, a micro calorimeter is required to realize power resolution of nW or below. However, the current microcalorimeter chip needs a complicated micromachining process, in addition, the microcalorimeter chip working in a vacuum environment needs to encapsulate a water-based sample, which makes the chip processing process more complicated, and the temperature sensor processed based on the thin film technology has the problems of micromachining and material non-uniformity, so that the actual resistance of the temperature sensor is difficult to be completely consistent with the nominal resistance, namely, the resistance has certain dispersity. The difference in temperature sensor resistance must be compensated by external electronics, introducing noise sources into the system, such that the detection limit (limit of detection, LOD) of the system is high. Disclosure of Invention In view of the above, the present invention provides a microcalorimeter chip based on a flexible printed circuit process and a method for manufacturing the same. In order to achieve the above object, the present invention provides the following solutions: A microcalorimeter chip based on a flexible printed circuit process comprises a substrate, a virtual reaction cavity and a plurality of temperature sensitive units, wherein the virtual reaction cavity is arranged in a central detection area of the substrate and is used for wrapping a sample, the virtual reaction cavity is formed by adding mineral oil into the central detection area of the substrate subjected to oleophobic treatment, and the temperature sensitive units are arranged at the bottom of the central detection area of the substrate and are used for detecting the temperature of the sample in the reaction process. Alternatively, the substrate is made of polyimide film. Alternatively, the temperature sensitive unit employs a standardized Pt1000 thermal resistor or a semiconductor thermistor. Optionally, the substrate is a hollowed-out structure. The invention also provides a preparation method of the microcalorimeter chip based on the flexible printed circuit process, which comprises the following steps: Preparing a flexible polyimide substrate; welding a plurality of temperature sensitive units with the same nominal resistance value to corresponding positions of a substrate through a surface mounting technology; Mineral oil is added to the central detection zone of the substrate to form a virtual reaction chamber. Optionally, the preparation of the flexible polyimide substrate specifically includes: forming a required circuit pattern on the copper foil plate by adopting an etching process to obtain a patterned copper foil plate; Placing the patterned copper foil plate and the polyimide film into a pressing machine for hot-press bonding to obtain a flexible circuit board; Machining the flexible circuit board according to the design pattern by using a numerical control machine tool; And electroplating a nickel layer on the surface of the copper foil, and then electroplating a gold