A method for enhancing sensor chip sensitivity and reusability by covering with parylene
By growing a parylene film on a VCSEL sensor chip and removing it with a tetrahydrofuran solution, the problems of high cost and difficulty in reusing biosensors were solved, and the sensitivity of the sensor was improved and it became reusable.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- BEIJING UNIV OF TECH
- Filing Date
- 2022-12-27
- Publication Date
- 2026-07-03
AI Technical Summary
Existing biosensors suffer from high costs and difficulty in reusing, especially due to the high costs associated with precious metals and precision manufacturing processes, as well as the potential damage to sensor performance caused by chemical or magnetic field treatments.
A 20 nm thick parylene film was grown on a VCSEL sensor chip as the sensing layer medium. The sensor was reused by combining chemical vapor deposition and tetrahydrofuran solution. The chemical stability and solubility of parylene were utilized, and the LSPR effect was combined to improve the sensor sensitivity.
This achieves improved sensor sensitivity and reusability, ensuring that the sensor surface remains undamaged during parylene removal and that performance remains consistent.
Smart Images
Figure CN116147766B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the fields of semiconductor photodetectors and biochemical sensing. Specifically, the method involves attaching a layer of parylene to a VCSEL sensing chip to improve the sensitivity of the sensing chip, and removing the parylene by immersion to make the sensing chip reusable. Background Technology
[0002] In recent years, biosensors have been widely researched and applied as disease diagnostic and analytical devices. They can convert external biological analytes into electrical or optical signals, thereby analyzing the type and concentration of the substances. The fabrication of most high-sensitivity biosensors and their nanostructured sensing layers requires precious metals and sophisticated processing techniques, resulting in very high costs, which is one of the major obstacles to their application. Therefore, if the chip can be reused, it will significantly reduce the cost of optical biosensors and promote their application. One method for chip reuse involves chemically removing residual antibodies and then using new antibodies for additional detection (Hsu, H.-F.; Lin, Y.-T.; Huang, Y.-T.; Lu, M.-F.; Chen, C.-H. In Situ Regeneration of Si-Based ARROW-B Surface Plasmon Resonance Biosensors. J. Med. Biol. Eng. 2015, 35, 305-314.). However, this chemical treatment may contaminate the sensor surface and degrade sensor performance. An external magnetic field is used to remove a layer of magnetic particles trapped on a solid substrate, and a new layer of magnetic particles is fixed on the chip surface for additional sensing (Yoo, H.; Shin, J.; Sim, J.; Cho, H.; Hong, S. Reusable Surface Plasmon Resonance Biosensor Chip for the Detection of H1N1 Influenza Virus. Biosens. Bioelectron. 2020, 168, 112561.). However, the introduction of a magnetic field increases the complexity of the sensing system. Therefore, we need to develop a simpler and more efficient method to make biosensors reusable. Parylene is a polymer material with excellent chemical stability and low thermal conductivity, often used as a thermal insulation material, and it can be grown on any material surface. Parylene can effectively adsorb antibodies. If it is used as a binding medium between the chip and the antibody, it can be dissolved and removed with a suitable solvent after measurement, thus achieving the purpose of chip reuse. Therefore, we demonstrated through testing different concentrations of NaCl solution that coating the sensitive layer of the sensor chip with parylene resulted in higher sensitivity than not coating it with parylene. Furthermore, we used tetrahydrofuran (THF) immersion to remove parylene without damaging the sensing surface of the VCSEL biosensor, and the experimental results proved that the chip can be reused using parylene. Summary of the Invention
[0003] This invention aims to provide a method for improving the sensitivity of biosensors and making high-cost chips reusable. The method involves growing parylene using chemical vapor deposition and a special coating system (PDS2010 type). Parylene is grown on a sensing layer (gold nanograting) above the light-emitting aperture of a VCSEL. Because the gold nanograting exhibits the LSPR effect, it can highly sensitively detect changes in the refractive index of the external environment. Therefore, the optical power (PIV) curves of different concentrations of NaCl solutions were first obtained by measuring the PIV curves on a VCSEL sensor chip without parylene growth. Then, parylene was grown on the same sensor chip, and the PIV curves of different NaCl solution concentrations were tested again. By comparing the PIV curves obtained before and after the tests, it can be found that the measured power is higher and the change is greater after growing parylene on the sensor chip, resulting in a higher sensitivity response. Furthermore, after immersing the chip in tetrahydrofuran solution for 6 hours, the parylene film was softened and loosened from the surface of the sensing layer by ultrasonication with ethanol. The power curve after removing parylene was found to be basically the same as the power curve obtained in the initial test, indicating that the substrate surface was protected and undamaged, and no intermediate derivatives were generated during the removal process.
[0004] The process features of this invention are as follows: First, a gold grating nanostructure is etched on the light-emitting end face of the laser. The fabricated polydimethylsiloxane (PDMS) is then integrated with the VCSEL chip using a fixture. Next, different concentrations of NaCl solutions are added to the PDMS reservoir, and the optical power is tested and recorded. After testing, the solution is cleaned with deionized water before further testing and recording. Then, parylene is grown on the nanostructure on the light-emitting end face of the VCSEL. After growth, the aforementioned series of tests using different concentrations of NaCl solutions are performed and recorded.
[0005] ① The fixture is a fixture designed specifically for VCSELs and suitable for chip layout. Its upper fixture has the same structure as PDMS, so that there is a liquid reservoir above the VCSEL to be tested to store the solution to be tested.
[0006] ② The NaCl concentrations were configured as 5%, 10%, 15%, 20%, and 25%, and their refractive indices were 1.3424, 1.3516, 1.3609, 1.3701, and 1.3793, respectively.
[0007] ③ The thickness of the grown parylene is 20 nm.
[0008] The experimental preparation process mainly involves the following steps: First, a gold grating structure is etched on the light-emitting end face of the VCSEL sensor chip. The VCSEL and PDMS are integrated using a fixture. Different concentrations of NaCl solutions are sequentially added to the reservoir using a hand pipette for the first PIV test, and the results are recorded. After the test, the chip is rinsed thoroughly with deionized water. Second, parylene is grown on the VCSEL sensor chip. The NaCl solution is tested again on its original laser. After the test, parylene is removed using tetrahydrofuran. Third, the NaCl solution is tested again on the same laser. By processing the test data, it can be found that the power curve obtained after growing parylene with the same NaCl solution has higher sensitivity than the power curve obtained before growth. Furthermore, after removing parylene, the power curve and sensitivity of the same NaCl solution are almost identical to those obtained in the first test, indicating that parylene has been almost completely removed and parylene can be grown again for repeated testing.
[0009] The innovation of this invention lies in using parylene as an intermediate linker between the VCSEL sensing layer and the test solution. It can not only be reused by removing and regenerating it, but also improve the sensitivity of the sensing chip. Attached Figure Description
[0010] Figure 1 Overall test flowchart.
[0011] In the diagram: 1.1 - Gold grating; 1.2 - VCSEL sensor chip; 1.3 - NaCl solution; 1.4 - PDMS; 1.5 - Parylene. ① The gold grating structure was etched using FIB; ② After covering with PDMS, different concentrations of NaCl solutions were tested for the first time; ③ After rinsing the sensor chip with deionized water, parylene was grown on the nanostructure; ④ The grown VCSEL was covered with PDMS, and different concentrations of NaCl solutions were tested again; ⑤ After testing, it was removed by soaking in tetrahydrofuran, allowing for repeated testing and reuse.
[0012] Figure 2 Results of optical power and sensitivity tests on NaCl solutions of different concentrations on a gold grating and after covering and removing parylene.
[0013] In the figure: 2.1 - The first test of PIV of different concentrations of NaCl solution after grating is completed; 2.2 - The sensitivity fit of 2.1; 2.3 - The PIV of different concentrations of NaCl solution measured after growing parylene on the gold grating; 2.4 - The sensitivity corresponding to 2.3; 2.5 - The optical power curves of different concentrations of NaCl solution measured again after removing parylene; 2.6 - The sensitivity corresponding to 2.5.
[0014] Figure 3 The optical power curves and sensitivity curves of three different concentrations of NaCl solution were combined into one graph for comparison.
[0015] In the figure: 3.1 - Optical power curves of NaCl in three tests; 3.2 - Optical power histograms of NaCl solutions in three tests; 3.3 - Corresponding sensitivity of the three tests. Detailed Implementation
[0016] The method proposed in this invention, which enables the reuse of sensor chips and improves sensing sensitivity, is implemented as follows:
[0017] 1. First, 10nm Ti and 50nm AU are sputtered onto the light-emitting end face of the VCSEL. The desired grating structure for sensing is then etched using a FIB focused ion beam. An initial PIV test is performed to determine whether the measured object has been cleaned by comparing the test data later.
[0018] 2. By preparing NaCl solutions with concentrations of 5%, 10%, 15%, 20%, and 25% using deionized water, the corresponding refractive indices are 1.3424, 1.3516, 1.3609, 1.3701, and 1.3793, respectively.
[0019] 3. PDMS is placed over the VCSEL sensor chip. PDMS prepolymer is prepared using a high-precision electronic balance with a PDMS:hardener ratio of 10:1. After preparation, the prepolymer is stirred for at least 3-5 minutes to fully integrate the two materials. After stirring, the PDMS prepolymer is placed in a vacuum chamber for approximately 30 minutes to defoam. The PDMS prepolymer is then transferred to a master mold wrapped in aluminum foil and heated on a heating plate at 80°C for curing. Once formed, the PDMS prepolymer is removed and allowed to cool to room temperature before demolding. Finally, the PDMS is integrated with the VCSEL sensor chip using a fixture.
[0020] 4. Using a hand pipette, sequentially add the prepared NaCl solutions of different concentrations into the storage tank. Then, using the testing system, record the optical power curves of the sensor chip after introducing NaCl solutions of different concentrations.
[0021] 5. After testing with different concentrations of NaCl solution, rinse repeatedly with deionized water. By testing the optical power curve, until the optical power is almost the same as the power when the grating was first etched, it indicates that the VCSEL sensor chip has been cleaned.
[0022] 6. The VCSEL sensor chip cleaned in the previous step is used to grow 20nm parylene through chemical vapor deposition and a special coating system (PDS2010 type). Then, the PIV curves are tested with different concentrations of NaCl solution.
[0023] 7. After testing the NaCl solution on parylene, the VCSEL sensor chip containing parylene and NaCl was immersed in tetrahydrofuran solution for 6 hours, and then sonicated in ethanol for 15 minutes to remove parylene. The optical power curve was measured again, and it was almost identical to the power measured in the first measurement of the gold grating, indicating that parylene and the NaCl on its surface had been removed and the chip could be reused.
[0024] 8. The power curves obtained by measuring different concentrations of NaCl solution again with VCSEL after removing parylene were compared with the power measured in the first measurement without the growth of parylene.
Claims
1. A method for covering parylene to improve the sensitivity and reusability of a sensing chip, characterized in that: (1) A layer of parylene is grown on the light-emitting end face of the laser with the prepared nanostructure as a connection layer between the sensing chip and the substance to be tested; (2) Prepare NaCl solutions of different concentrations as the test substances; (3) Integrate the VCSEL sensor chip with polydimethylsiloxane PDMS using a fixture, feed the prepared NaCl solution into it, and measure its PIV curve; (4) After removing parylene, test the optical power curve of the same NaCl solution again; (5) Process the data, compare them, and draw preliminary conclusions.
2. The method of claim 1, wherein the parylene coating improves the sensitivity and reusability of the sensor chip. A 20-nanometer-thickness parylene film was grown on the laser end face. Simulation results showed that the 20-nanometer parylene film had the best effect on improving sensitivity.
3. The method for enhancing sensor chip sensitivity and reusability by covering with parylene according to claim 1, characterized in that: The NaCl solution was removed by repeated rinsing with deionized water. Therefore, by testing different concentrations of NaCl solution, it is possible to confirm that growing parylene improves the sensitivity of the sensor chip and also to demonstrate its reusability.
4. The method for enhancing sensor chip sensitivity and reusability by covering with parylene according to claim 1, characterized in that: The NaCl solutions were prepared with concentrations of 5%, 10%, 15%, 20%, and 25%, and their corresponding refractive indices increased sequentially to 1.3424, 1, 3516, 1.3609, 1.3701, and 1.3793, respectively.
5. The method for enhancing sensor chip sensitivity and reusability by covering with parylene according to claim 1, characterized in that: The prepared NaCl solutions were pipetted from low to high concentration into the storage tank, and the power curves were recorded sequentially.
6. The method for enhancing sensor chip sensitivity and reusability by covering with parylene according to claim 1, characterized in that: Parylene was removed by soaking in tetrahydrofuran solution for 6 hours, followed by ultrasonic oscillation with ethanol to remove the parylene film and the analyte on it.