Although blood-biomarker-based tests help in the early diagnosis of Alzheimer’s disease, the low abundance of blood protein biomarkers related to Alzheimer’s disease and the complexity of the human serum environment pose a challenge in diagnosis and treatment.
Due to the small size of nanomaterials, they are considered promising candidates for constructing biosensors with high sensitivity. Moreover, fabricating nanomaterials-containing transistor-based biosensors is challenging on a large scale and often lacks sensitivity and reproducibility in complex physiological fluids.
In an article recently published in the journal ACS Sensors, mass production of field-effect transistor (FET) biosensors based on carbon nanotube thin films was reported to realize high selectivity and sensitivity toward the detection of Alzheimer’s disease blood biomarkers of beta (β)-amyloid (Aβ).
The mass-produced carbon nanotube FET-sensors were combined with oligonucleotide aptamers to achieve efficient bioreceptors that enable reproducible and reliable Aβ42 and Aβ40 peptide detection in human serum with sub-femtomolar detection sensitivity, thus outperforming other existing detection methods towards Alzheimer’s disease.
Application of Carbon Nanotube Network Films Toward Alzheimer’s Disease Detection
Alzheimer’s disease is the common cause of dementia and leads to progressive cognitive decline. Moreover, Alzheimer’s disease is incurable and irreversible after the outset of cognitive symptoms. Hence, early diagnosis and disease-modifying treatments before the onset of symptoms are critical for Alzheimer’s disease treatment.
In Alzheimer’s disease diagnosis, Aβ protein level measurement in cerebrospinal fluid (CSF) and Aβ positron emission tomography (PET) imaging are currently applied detection methods. However, these are not extensively applied because obtaining CSF fluid involves an invasive lumbar puncture, and PET imaging is an expensive procedure.
To this end, diagnosis based on Alzheimer’s disease blood biomarkers can be a better alternative to previously mentioned methods due to simple peripheral blood sample requirement, minimal invasion, and the low cost of the procedure. However, the low concentration of Alzheimer’s disease proteins in the blood, the significant presence of interferants in the blood that cause masking effects, and protein’s large dynamic range are a few challenges posed by Alzheimer’s disease blood biomarkers-based diagnosis.
Nanomaterials-based FET sensors are next-generation, highly sensitive, and label-free methods with high- integration capability. Despite the outstanding performance of nano-FET sensors, their clinical application for blood-based biomarkers detection remains challenging to facilitate their application in diagnosing Alzheimer’s disease.
Semiconducting carbon nanotube network films are promising nanomaterials to construct FET biosensors with ultra-sensitivity. However, large-scale fabrication of carbon nanotube FET-based biosensors to detect ultralow biomarker concentrations with quick response in complex physiological environments remains unexplored.
Aptamer-Functionalized Carbon Nanotube FET Biosensors for Alzheimer’s Disease Diagnosis
In the present work, carbon nanotube FETs functionalized with nucleic acid aptamers were manufactured via a high-throughput fabrication process. In doing so, the team was able to achieve a highly selective and sensitive biosensor array for detecting Aβ proteins in serum at low concentrations and thereby promoting the clinical application of carbon nanotube FET-based sensor in early diagnosis of Alzheimer’s disease.
This FET sensor leverages the advantages of semiconducting carbon nanotube network film and DNA aptamers that are modified on a floating gate (FG) insulator. These modified DNA aptamers serve as Aβ40 and Aβ42 peptide selective receptors for the early detection of Alzheimer’s disease.
DNA aptamer-functionalized carbon nanotube FETs can detect Aβ40 and Aβ42 peptides in undiluted serum and single-strength phosphate buffer saline with a limit of detection (LoD) of 50 attomoles. The DNA aptamer-functionalized carbon nanotube FET sensors were highly selective towards Aβ peptides, immunoglobin G (IgG), and albumin masking proteins. Thus, carbon nanotube FET sensors outperform other Alzheimer’s disease sensing methods.
Moreover, the biological substrate’s adsorption to carbon nanotube FET biosensor has enhanced the selectivity ratios of up to 800% (Aβ42) and 730% (Aβ40). The DNA aptamer-functionalized carbon nanotube FET biosensor showed a quick response, wide dynamic range, low variation, and reduced overall cost, making this rapid detection method applicable for mass screening and early diagnosis of Alzheimer’s disease.
Conclusion
To summarize, aptamer-functionalized carbon nanotube FET biosensors were fabricated and explored for early diagnosis of Alzheimer’s disease by detecting the corresponding serum biomarkers in undiluted and single-strength PBS human serum. The aptamer-functionalized carbon nanotube FETs showed a broad analytical range with LoDs as low as 45 attomoles for Aβ42 and 55 attomoles for Aβ40.
The multi-blocking step reduced the nonspecific adsorption of biological matrix on aptamer-functionalized carbon nanotube FETs. Despite the presence of structurally similar proteins in the biological matrix solution, the selectivity ratio was improved by 800%. Moreover, these aptamer-functionalized carbon nanotube FETs showed a high recovery rate of 88 to 108%, high accuracy, serum-based long-term stability, and high reproducibility with less than 10% device-to-device variation.
Due to the high reliability and outstanding sensing properties, aptamer-functionalized carbon nanotube FET biosensors showed great potential as a cost-effective, reliable, and quick clinical platform, contributing toward advancements in mass screening tests and early diagnosis for Alzheimer’s disease.
News
NIH Scientists Discover Gene Responsible for Rare Eye Disease
Findings supported by the NIH pave the way for the development of genetic testing, clinical trials, and therapies. Researchers at the National Institutes of Health (NIH) and their collaborators have discovered a gene linked to certain [...]
Alzheimer’s Breakthrough: Synthetic THC Pill Proves Effective in Clinical Trial
Patients tolerated synthetic THC (dronabinol) well, without the adverse effects commonly associated with existing Alzheimer’s agitation medications. A study conducted by researchers from Johns Hopkins University School of Medicine and Tufts University School of Medicine found that a pill form [...]
The Future of Rare Disease Treatment with Precision Medicine
Understanding rare diseases Rare diseases affect less than 5 people out of 10,000. However, this still amounts to about 7% of the world’s population, with over 10,000 such conditions. Almost all are genetic in [...]
Doctors issue warning for upcoming ‘tripledemic
The term ‘tripledemic’ has hit headlines this week as the NHS begins its Covid and fluvaccine roll-out for vulnerable adults. As the cold weather sets in, many of us have experienced a decline in health, and this may [...]
The FDA approved a gel that can stop bleeding from wounds in seconds
Aug 15 (Reuters) - The U.S. Food and Drug Administration has cleared Cresilon's gel to quickly control bleeding, the privately held company said on Thursday, potentially giving emergency medical technicians and combat medics a [...]
High levels of microplastics found in prostate tumors, possibly linked to take-out food
The presence of microplastics in prostate tumors points to potential health risks, and researchers are calling for urgent studies to explore how take-out food may be driving this exposure. In a recent study published [...]
AI outperforms radiologists in brain tumor diagnosis
As artificial intelligence advances, its uses and capabilities in real-world applications continue to reach new heights that may even surpass human expertise. In the field of radiology, where a correct diagnosis is crucial to ensure [...]
Breakthrough Study Reveals Molecular Clues to Dementia Origins
Work could lead to the discovery of new therapeutic targets. For the first time, researchers have identified “molecular markers” linked to degeneration—detectable changes in cells and their gene-regulating networks—that are common across several types [...]
Better than blood tests? Nanoparticle potential found for assessing kidneys
In a study published July 29 in Advanced Materials, University of Texas at Dallas researchers found that X-rays of the kidneys using gold nanoparticles as a contrast agent might be more accurate in detecting kidney [...]
Greener nanomaterials could transform how our everyday stuff is made
Tiny nanoparticles are at the forefront of materials science—with special properties that make them great at absorbing light in solar panels, cleaning wastewater, and delivering drugs precisely. Some nanoparticles take the form of sheets or fibers. But nanomaterials all [...]
AI could predict breast cancer risk via ‘zombie cells’
Women worldwide could see better treatment with new AI technology, which enables better detection of damaged cells and more precisely predicts the risk of getting breast cancer, shows new research from the [...]
Through the eyes of a cat – biomimicry of feline eyes may revolutionize robotic vision
In a recent study published in the journal Science Advances, researchers leveraged crucial aspects of feline eyes, particularly their tapetum lucidum and vertically elongated pupils (VP), to develop a monocular artificial vision system capable of [...]
New Alzheimer’s Therapy Shows Remarkable Results in Animal Trials
A study from TUM demonstrates a promising therapeutic approach. Researchers at the Technical University of Munich (TUM) have made promising advances in preventing Alzheimer’s by developing a new therapeutic strategy. Their approach focuses on targeting the amyloid beta [...]
Rewriting Cancer’s Blueprint: New Study Challenges Old Theories
A new study argues for a revised clonal evolution model of cancer, incorporating genetic and non-genetic factors to improve understanding and treatment. Like all living organisms, cancer cells are driven by the fundamental need [...]
Microplastics Everywhere: Experts Demand Worldwide Treaty Before It’s Too Late
A new report calls for global action on plastic pollution, urging reductions in plastic production and microplastic emissions. Researchers stress the importance of addressing plastic pollution through both scientific and social science perspectives. A [...]
Blood tests could soon predict your risk of Alzheimer’s
Scientists are closing in on biomarkers that reflect the progression of Alzheimer’s disease and could improve treatments. Like many Alzheimer’s researchers, neurologist Randall Bateman is not prone to effusiveness, having endured disappointments in his [...]
