WO2024144689A2 - Development of a new electrochemical sensor for the diagnosis of parkinson's disease from real samples - Google Patents
Development of a new electrochemical sensor for the diagnosis of parkinson's disease from real samples Download PDFInfo
- Publication number
- WO2024144689A2 WO2024144689A2 PCT/TR2023/051704 TR2023051704W WO2024144689A2 WO 2024144689 A2 WO2024144689 A2 WO 2024144689A2 TR 2023051704 W TR2023051704 W TR 2023051704W WO 2024144689 A2 WO2024144689 A2 WO 2024144689A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- disease
- parkinson
- diagnosis
- sample
- sweat
- Prior art date
Links
- 208000018737 Parkinson disease Diseases 0.000 title description 12
- 238000003745 diagnosis Methods 0.000 title description 12
- 238000011161 development Methods 0.000 title description 2
- 238000000034 method Methods 0.000 claims description 7
- 239000011521 glass Substances 0.000 claims description 5
- 238000005259 measurement Methods 0.000 claims description 3
- 230000008021 deposition Effects 0.000 claims description 2
- 238000000151 deposition Methods 0.000 claims 2
- 238000009718 spray deposition Methods 0.000 claims 1
- 210000004243 sweat Anatomy 0.000 description 18
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 16
- 239000000523 sample Substances 0.000 description 16
- 201000010099 disease Diseases 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 229960003638 dopamine Drugs 0.000 description 8
- 239000010409 thin film Substances 0.000 description 8
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 5
- 229960004373 acetylcholine Drugs 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 238000013473 artificial intelligence Methods 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 238000003759 clinical diagnosis Methods 0.000 description 2
- 239000013068 control sample Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000003291 dopaminomimetic effect Effects 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- 241001573498 Compacta Species 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 238000004082 amperometric method Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000004579 marble Substances 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Definitions
- Parkinson's disease is a disease that is usually seen in individuals over the age of 60 and affects individuals with neurodegenerative damage. Most of the findings relating to diagnosis of Parkinson's disease are provided by data obtained as a result of a number of experiments. Among these, the determination of symptoms is based on data obtained from force sensors collected by attaching them to the soles of the feet.
- Parkinson's disease is based on the identification of features related to dopamine deficiency, which is a result of degeneration of the substantia nigra pars compacta. Additionally, non-dopaminergic and non-motor symptoms are sometimes present before diagnosis and almost inevitably occur with disease progression. Non-motor symptoms dominate the clinical picture of advanced Parkinson's disease and contribute to severe disability, impaired quality of life, and shortened life expectancy.
- the change in the amount of dopamine and acetylcholine in the unknown sample will be determined with the calibration curve equation that will be obtained as a result of monitoring the change in flow by using very low volume sweat samples such as 10 pL. It is related to the easy clinical diagnosis of Parkinson's disease by the person herself/himself or by the physicians Detailed Description of the Invention
- the change as a result of applying a constant current to a 10 mL sweat sample taken from individuals by the amperometric method will be determined and the amount of dopamine and acetylcholine in the patient samples will be determined by using the equation of standard graphs obtained from the current-time graphs of dopamine and acetylcholine substances of known amounts.
- FeO thin film layers were formed by the USP-Spray spraying method.
- the amount of dopamine, the amount of acetylcholine and the current change related to the amount of dopamine and acetylcholine in sweat samples are determined by using an amperometer.
Landscapes
- Investigating Or Analysing Biological Materials (AREA)
Description
DEVELOPMENT OF A NEW ELECTROCHEMICAL SENSOR FOR THE DIAGNOSIS OF PARKINSON'S DISEASE FROM REAL SAMPLES
Technical Field
This invention enables disease diagnosis in samples taken from physiological samples during diseases. However, there is no diagnosis of Parkinson's disease from any known sample. Our patent proposal relates to a method to be used to develop sensors for the diagnosis of the disease from sweat samples of Parkinson patients.
Prior Art
Parkinson's disease is a disease that is usually seen in individuals over the age of 60 and affects individuals with neurodegenerative damage. Most of the findings relating to diagnosis of Parkinson's disease are provided by data obtained as a result of a number of experiments. Among these, the determination of symptoms is based on data obtained from force sensors collected by attaching them to the soles of the feet.
Clinical diagnosis of Parkinson's disease is based on the identification of features related to dopamine deficiency, which is a result of degeneration of the substantia nigra pars compacta. Additionally, non-dopaminergic and non-motor symptoms are sometimes present before diagnosis and almost inevitably occur with disease progression. Non-motor symptoms dominate the clinical picture of advanced Parkinson's disease and contribute to severe disability, impaired quality of life, and shortened life expectancy.
Unlike dopaminergic symptoms of the disease that the treatment is available, non-motor symptoms are not often recognized enough and inadequately treated.
The main diagnostic methods currently available for Parkinson's disease are traditional empirical diagnosis by doctors and the use of artificial intelligence to help diagnose the disease. However, diagnosis by physicians is a timeconsuming and labor-intensive approach, and even if the number of patients that can be diagnosed in a weekly outpatient clinic is limited for doctors, many tests are often required for patients to support the diagnosis.
There are some studies carried out in the field. However, all of them are more related to monitoring the differentiation of hand and foot behaviors and detecting this with artificial intelligence. In addition, it is aimed to keep the dopamine level in the blood constant due to continuous drug use since the beginning of the disease. No sensors have been developed to detect dopamine levels in the course of the disease. However, it can only be detected in body samples taken (blood, serum, plasma, etc.) using chromatographic devices such as HPLC, LC- MS.
This invention will make it possible to detect a small amount of sweat sample, such as 10 pL, which can be easily obtained physiologically, by dropping it onto the electrode surface with a sensor system based on current change. This aspect relates to the method of using the sensor at the bedside of patients.
Brief Description of the Invention
This invention offers a sensor that will eliminate the difficulties experienced in the diagnosis of Parkinson's disease and enable simple, easy and bedside use from sweat samples.
The change in the amount of dopamine and acetylcholine in the unknown sample will be determined with the calibration curve equation that will be obtained as a result of monitoring the change in flow by using very low volume sweat samples such as 10 pL. It is related to the easy clinical diagnosis of Parkinson's disease by the person herself/himself or by the physicians
Detailed Description of the Invention
With this invention, the change as a result of applying a constant current to a 10 mL sweat sample taken from individuals by the amperometric method will be determined and the amount of dopamine and acetylcholine in the patient samples will be determined by using the equation of standard graphs obtained from the current-time graphs of dopamine and acetylcholine substances of known amounts.
Parkinson's disease, which has not yet been diagnosed in the clinic, will be diagnosed. Within the scope of this invention, the synthesis of molecules containing primary carbamate groups with a new method are as follows;
FeO thin film layers formed by the SI LAR method on the glass silica surface will be used in the diagnosis of Parkinson's disease. For this purpose, the glass plate was dipped in FeCI2 solution, then dipped in ammonia solution, and in the last stage, it was washed with pure water. After Cycle 1 was completed, Cycle 2 was started and repeated. This process was repeated until the deposition of FeO NPs on the surface was completed. The process steps are summarized in Figure 1.
In addition, FeO thin film layers were formed by the USP-Spray spraying method. The amount of dopamine, the amount of acetylcholine and the current change related to the amount of dopamine and acetylcholine in sweat samples are determined by using an amperometer.
10 pL samples were dropped each time onto the FeO thin films placed on the marble surface, which was specially made for the device used for this purpose, and the current change was monitored on the connected computer screen as a result of the constant current applied with the Keithley 2002 8.5 Digit Multimeter with Scanning, USA device. The results are given with the Current-Time graph.
Measurements were taken before and after adding the sample and the changes were calculated using the following formula:
S: % Sensivity krst: The current value shown by the empty sample before the sweat sample was dropped. hast: It refers to the current value passing through the sample after the sweat sample is dropped.
First of all, before dropping the sweat sample onto this contact film, a constant voltage was applied for approximately 150 s, and the change in the current passing through the sample was measured depending on time. Then, 10 pL sweat samples are dropped equally onto the FeO nanostructured thin film structures and followed for 150 seconds to perform sweat detection analyzes by means of the change in current.
It is about taking measurements of sweat samples obtained for samples of five different concentrations, ordered from low concentration to high concentration.
When the flow change graph obtained from the control sample is compared with the graph of Parkinson's patients, it is determined that there is a difference in both formal and perceived current values.
While it is observed that there was an increase in the current value as a result of dropping small amounts of sweat sample, such as 10 pL, into the nanostructured FeO thin film structure, when the concentration goes from 1 mg/mL to 0.0001 mg/mL, it was determined that the detection performance was also significantly affected and its response increased in direct proportion to the increase in sweat concentration.
Graph of the change of current passing over the sample depending on time, formed by dropping a healthy person sweat sample at a concentration of 1 - 0.0001 mg/mL onto the nano-structured FeO thin film structure.
Graph of the change of current passing over the sample depending on time, formed by dropping sweat samples from Parkinson's patients (A: 1st Parkinson's patient, B: 2nd Parkinson's patient) at a concentration of 1 -0.0001 mg/mL onto the nano-structured FeO thin film structure.
When the flow change graph obtained from the control sample was compared with the graph of Parkinson's patients, it was determined that there was a difference in both formal and perceived current values.
While it is observed that there is an increase in the current value as a result of dropping small amounts of sweat sample, such as 10 pL, into the nano-structured FeO thin film structure, when the concentration goes from 1 mg/mL to 0.0001 mg/mL, it was about that the perception performance is also significantly affected and its response increases in direct proportion to the increase in sweat concentration.
Claims
1. Creation of smooth surfaces by depositing FeO NP on glass surfaces cleaned by SI LAR method or, USP - FeO deposition on glass surfaces at 400 °C by spray deposition on glass surfaces, characterized in that; prevent contact with the electrodes when the sample is dripped on the surfaces and direct current application, measurements are made before and after the sample is added and the significance of the results is determined by comparing the results with standard graphs.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2022022096 | 2022-12-31 | ||
| TR2022/022096 TR2022022096A2 (en) | 2022-12-31 | DEVELOPMENT OF A NEW ELECTROCHEMICAL SENSOR FOR THE DIAGNOSIS OF PARKINSON'S DISEASE FROM REAL SAMPLES |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2024144689A2 true WO2024144689A2 (en) | 2024-07-04 |
Family
ID=91719363
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/TR2023/051704 WO2024144689A2 (en) | 2022-12-31 | 2023-12-26 | Development of a new electrochemical sensor for the diagnosis of parkinson's disease from real samples |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2024144689A2 (en) |
-
2023
- 2023-12-26 WO PCT/TR2023/051704 patent/WO2024144689A2/en unknown
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