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Blood-Based Multiplexed Diagnostic Sensor Helps to Accurately Detect Alzheimer’s Disease
A research team at KAIST reported clinically accurate multiplexed electrical biosensor for detecting Alzheimer’s disease by measuring its core biomarkers using densely aligned carbon nanotubes. Alzheimer’s disease is the most prevalent neurodegenerative disorder, affecting one in ten aged over 65 years. Early diagnosis can reduce the risk of suffering the disease by one-third, according to recent reports. However, its early diagnosis remains challenging due to the low accuracy but high cost of diagnosis. Research team led by Professors Chan Beum Park and Steve Park described an ultrasensitive detection of multiple Alzheimer's disease core biomarker in human plasma. The team have designed the sensor array by employing a densely aligned single-walled carbon nanotube thin films as a transducer. The representative biomarkers of Alzheimer's disease are beta-amyloid42, beta-amyloid40, total tau protein, phosphorylated tau protein and the concentrations of these biomarkers in human plasma are directly correlated with the pathology of Alzheimer’s disease. The research team developed a highly sensitive resistive biosensor based on densely aligned carbon nanotubes fabricated by Langmuir-Blodgett method with a low manufacturing cost. Aligned carbon nanotubes with high density minimizes the tube-to-tube junction resistance compared with randomly distributed carbon nanotubes, which leads to the improvement of sensor sensitivity. To be more specific, this resistive sensor with densely aligned carbon nanotubes exhibits a sensitivity over 100 times higher than that of conventional carbon nanotube-based biosensors. By measuring the concentrations of four Alzheimer’s disease biomarkers simultaneously Alzheimer patients can be discriminated from health controls with an average sensitivity of 90.0%, a selectivity of 90.0% and an average accuracy of 88.6%. This work, titled “Clinically accurate diagnosis of Alzheimer’s disease via multiplexed sensing of core biomarkers in human plasma”, were published in Nature Communications on January 8th 2020. The authors include PhD candidate Kayoung Kim and MS candidate Min-Ji Kim. Professor Steve Park said, “This study was conducted on patients who are already confirmed with Alzheimer’s Disease. For further use in practical setting, it is necessary to test the patients with mild cognitive impairment.” He also emphasized that, “It is essential to establish a nationwide infrastructure, such as mild cognitive impairment cohort study and a dementia cohort study. This would enable the establishment of world-wide research network, and will help various private and public institutions.” This research was supported by the Ministry of Science and ICT, Human Resource Bank of Chungnam National University Hospital and Chungbuk National University Hospital. < A schematic diagram of a high-density aligned carbon nanotube-based resistive sensor that distinguishes patients with Alzheimer’s Disease by measuring the concentration of four biomarkers in the blood. > Profile: Professor Steve Park firstname.lastname@example.org Department of Materials Science and Engineering http://steveparklab.kaist.ac.kr/ KAIST Profile: Professor Chan Beum Park parkcb at kaist.ac.kr Department of Materials Science and Engineering http://biomaterials.kaist.ac.kr/ KAIST
Light Driven Drug-Enzyme Reaction Catalytic Platform Developed
Low Cost Dye Used, Hope for Future Development of High Value Medicinal Products to Treat Cardiovascular Disease and Gastric Ulcers A KAIST research team from the Departments of Materials Science and Engineering and of Chemical and Biomolecular Engineering, led respectively by Professors Chan Beum Park and Ki Jun Jeong, has developed a new reaction platform to induce drug-enzyme reaction using light. The research results were published in the journal Angewandte Chemie, International Edition, as the back cover on 12 January 2015. Applications of this technology may enable production of high value products such as medicine for cardiovascular disease and gastric ulcers, for example Omeprazole, using an inexpensive dye. Cytochrome P450 is an enzyme involved in oxidative response which has an important role in drug and hormone metabolism in organisms. It is known to be responsible for metabolism of 75% of drugs in humans and is considered a fundamental factor in new drug development. To activate cytochrome P450, the enzyme must receive an electron by reducing the enzyme. In addition, NADPH (a coenzyme) needs to be present. However, since NADPH is expensive, the use of cytochrome P450 was limited to the laboratory and has not yet been commercialized. The research team used photosensitizer eosin Y instead of NADPH to develop “Whole Cell Photo-Biocatalysis” in bacteria E. coli. By exposing inexpensive eosin Y to light, cytochrome P450 reaction was catalyzed to produce the expensive metabolic material. Professor Park said, “This research enabled industrial application of cytochrome P450 enzyme, which was previous limited.” He continued, “This technology will help greatly in producing high value medical products using cytochrome P450 enzyme.” The research was funded by the National Research Foundation of Korea and KAIST's High Risk High Return Project (HRHRP). Figure 1: Mimetic Diagram of Electron Transfer from Light to Cytochrome P450 Enzyme via Eosin Y, EY Figure 2: The back cover of Angewandte Chemie published on 12 January 2015, showing the research results
Professor Chan Beum Park, requested for joint international research by a German biotechnology enterprise.
- Bitop AG (Germany) requested a joint development of medicines for Alzheimer’s disease - The meaning of the financial support by European enterprise to the research result of domestic university. Professor Chan Beum Park (Department of Materials Science and Engineering in KAIST/ President Nam Pyo Suh) has been entrusted with a joint international research for the development of medicines for Alzheimer’s disease from Bitop AG, German biotechnology enterprise. KAIST recently agreed with Bitop AG to cooperate for a research program pursuing the development of inhibitors that inhibit the formation of plaque relevant to amyloid diseases like Alzheimer’s disease. Based on this agreement, KAIST will be provided with a financial support of sixty thousands Euro (about 74 million won) from Bitop AG. Professor Park will perform the screening of inhibitors, which are the core of the research, and KAIST will share patent rights from the research with Bitop AG. It is known that various degenerative nerve diseases like Alzheimer’s disease, Parkinson’s disease, mad cow disease, and so on arise mainly from the accumulation of pathological protein plaque termed amyloid, and environmental stress accelerates the diseases. So far, no effective remedy has been developed for amyloid diseases. Recently, the use of chemicals inhibiting the formation of amyloid has been raised as a potential remedy. Natural small stress molecules extracted from microbes growing in extreme environments like volcanic region on the bottom of the deep sea, etc. are gaining attention as an amyloid inhibitor. Professor Park found out for the first time in the world that Anti-stress materials are effective in inhibiting the formation of amyloid plaque and published that fact in several renowned European scientific journals. After that, Professor Park was requested by Bitop AG for a joint research and has studied for the development of medicines for Alzheimer’s disease using various kinds of Anti-stress materials. Professor Park said, “I’d like to grant a highly valuable meaning to this entrustment since it implies that European enterprises perceive the value of the research result by domestic universities and hope to promote research and development by providing practical financial support, etc. I wish this time’s entrustment will be a momentum to advance Korea’s research level one step higher through active joint researches with enterprises or institutes in U.S. and Europe as well as Bitop AG.” Bitop AG is a German enterprise that produces various Anti-stress materials coming from extreme-loving microbes. Currently, Anti-stress materials are being sold mainly as protein and cell protectants, cosmetic additives, health supplement, etc. Anti-stress materials extracted from microbes well growing in extreme environment of one hundred centigrade or more are expected to perform a role of inhibitors that inhibit the formation of amyloid plaque, the main factor of stress-related degenerative nerve diseases like Alzheimer’s disease, etc. Such Anti-stress materials are gaining attention as a future medicine for Alzheimer’s disease, etc.
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