Posted September 19, 2023

Dr. Tony Jun Huang, Duke University

From stethoscopes to ultrasounds, health care practitioners use sound technologies to determine the best way to treat their patients. Recent advancement in the field of acoustofluidics, a combination of acoustics (sound) and fluidics (how fluids move) may show promise in diagnosing neurodegenerative diseases.

Currently, Alzheimer’s disease and several other neurodegenerative disorders are diagnoses of exclusion, which means individuals must undergo several tests to rule out other potential disorders before they receive a diagnosis. This is a time-consuming process leading to delays in treatment and is often stated as an area of significant concern among those living with these disorders.

Dr. Tony Huang
Dr. Tony Huang
(Photo Provided)

Through a fiscal year 2017 (FY17) Convergence Science Research Award from the Peer-Reviewed Alzheimer’s Research Program, Dr. Tony Jun Huang, from Duke University, is addressing the need for more precise methods to diagnose neurodegenerative conditions. Several acoustofluidic devices developed by Dr. Huang’s research team demonstrate potential to aid in the diagnosis of neurological conditions such as Alzheimer’s disease and traumatic brain injury (TBI).

One device is an acoustofluidic multimodal diagnostic system to detect Alzheimer’s disease biomarkers, such as proteins, from human plasma. This approach first uses sound to remove microscopic contaminants from the raw plasma, preserving nanosized particles in a matter of seconds (Figure 1). The integrated system incorporates Alzheimer’s disease-specific antibodies (anti-Aß42 and anti-tau) to significantly improve the sensitivity, specificity, and accuracy of detection of nanosized Alzheimer’s disease-associated particles.

Dr. Tony Huang figure 1
Figure 1: Picture of the acoustofluidic separation chip for isolating biomarkers from biofluids such as plasma samples. Two separation modules arranged in series. Lower frequency (20 MHz) pair of transducers screen out micrometer-sized contaminants for the upstream separation module, whereas higher frequency (40 MHz) transducers at the downstream separation module screen out the submicrometer-sized contaminates. (Figure Provided)

A significant challenge with diagnostic technologies is that, in general, it is very difficult to detect the tiny amounts of biomarkers in patient blood. Alternative biofluids such as cerebrospinal fluid (CSF) utilize higher-risk collection procedures or other potential biosamples do not contain biomarker signatures at all. A key question therefore remains on what biomarkers can be detected in easy-to-obtain biosamples that help diagnose and perhaps prognose the development of dementia following TBI. To address this, Dr. Huang’s team developed an acoustofluidic device that separates bioparticles based on their size. This technology successfully isolated exosomes, a specific type of biomarker vesicles, from blood collected from a mouse model with TBI. The team successfully collected more higher-quality material in five minutes than conventional methods yield in over eight hours.

To demonstrate the utility of this device in aiding diagnosis following TBI, the investigators tested the amount of glial fibrillary acidic protein (GFAP), a biomarker associated with TBI, in their acoustically separated particles. Results show the number of GFAP-positive exosomes increased with time after TBI, in a matter of several hours to one day. These exosomes cannot be detected using unprocessed, conventional plasma samples. The much-improved sensitivity may aid in earlier diagnosis of TBI, Alzheimer’s disease, and other neurological conditions.

Dr. Huang and his team provide proof-of-concept data of the novel sound technology. With the ability to integrate with other diagnostic capabilities, the acoustofluidic devices have taken the first steps to point-of-care clinical diagnosis. Follow-on work from the PRARP award includes avenues for commercialization and collaboration worldwide supported by external sources. The new technologies have the potential to transform current diagnosis capabilities for TBIs, Alzheimer’s disease, and other dementias, making a positive impact for those living with these conditions and their families.

Gu Y, Chen C, Rufo J, et al. 2020. Acoustofluidic holography for micro- to nanoscale particle manipulation. ACS Nano 14(11):14635-14645. doi: 10.1021/acsnano.0c03754. Epub 2020. PMID: 32574491. PMCID: PMC7688555.

Gu Y, Chen C, Mao Z, et al. 2021. Acoustofluidic centrifuge for nanoparticle enrichment and separation. Sci Adv 7(1):eabc0467. doi: 10.1126/sciadv.abc0467. PMID: 33523836. PMCID: PMC7775782.

Wang Z, Wang H, Becker R, et al. 2021. Acoustofluidic separation enables early diagnosis of traumatic brain injury based on circulating exosomes. Microsyst Nanoeng 7:20. doi: 10.1038/s41378-021-00244-3. PMID: 34567734. PMCID: PMC8433131.

Hao N, Wang Z, Liu P, et al. 2022. Acoustofluidic multimodal diagnostic system for Alzheimer's disease. Biosens Bioelectron 196:113730. doi: 10.1016/j.bios.2021.113730. Epub 2021. PMID: 34736099. PMCID: PMC8643320.

Public and Technical Abstracts: Developing Biomarkers for Traumatic Brain Injury and Alzheimer's Disease via Acoustic Exosome Separation Devices

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