Acoustofluidic separation enables early diagnosis of traumatic brain injury based on circulating exosomes

Zeyu Wang,Mengxi Wu,Ryan Becker,Joseph Rufo,Tony Jun Huang,Shujie Yang,Jun Zou,Daniel T Laskowitz,Haichen Wang,Brian E Mace

doi:10.1038/s41378-021-00244-3

Zeyu Wang, Mengxi Wu + Show 8 more

Open Access

https://doi.org/10.1038/s41378-021-00244-3

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Abstract

Traumatic brain injury (TBI) is a global cause of morbidity and mortality. Initial management and risk stratification of patients with TBI is made difficult by the relative insensitivity of screening radiographic studies as well as by the absence of a widely available, noninvasive diagnostic biomarker. In particular, a blood-based biomarker assay could provide a quick and minimally invasive process to stratify risk and guide early management strategies in patients with mild TBI (mTBI). Analysis of circulating exosomes allows the potential for rapid and specific identification of tissue injury. By applying acoustofluidic exosome separation—which uses a combination of microfluidics and acoustics to separate bioparticles based on differences in size and acoustic properties—we successfully isolated exosomes from plasma samples obtained from mice after TBI. Acoustofluidic isolation eliminated interference from other blood components, making it possible to detect exosomal biomarkers for TBI via flow cytometry. Flow cytometry analysis indicated that exosomal biomarkers for TBI increase in the first 24 h following head trauma, indicating the potential of using circulating exosomes for the rapid diagnosis of TBI. Elevated levels of TBI biomarkers were only detected in the samples separated via acoustofluidics; no changes were observed in the analysis of the raw plasma sample. This finding demonstrated the necessity of sample purification prior to exosomal biomarker analysis. Since acoustofluidic exosome separation can easily be integrated with downstream analysis methods, it shows great potential for improving early diagnosis and treatment decisions associated with TBI.

Highlights

Traumatic brain injury (TBI) represents a significant public health issue in the United States and internationally[1]
Animal experiments indicated that after TBI treatment, the number of glial fibrillary acidic protein (GFAP) +/CD63+ exosomes in plasma increased over time, which suggests a potential role for exosomes as biomarkers for early screening and medical decisionmaking in patients with TBI
According to comparative tests using unprocessed plasma, an increase in GFAP+/CD63+ exosomes was not detected, suggesting that acoustofluidic separation played an important role in sample processing for exosome analysis

Summary

Introduction

Traumatic brain injury (TBI) represents a significant public health issue in the United States and internationally[1]. More than 50 million individuals are estimated to suffer from TBI annually, resulting in more than 50,000 deaths and 100,000 disabilities[2]. The complicated pathology and multiple forms of TBI result in unpredictable outcomes. Long-term complications from TBI—which include cognitive impairment, posttraumatic. Wang et al Microsystems & Nanoengineering (2021)7:20 unclear or minor symptoms do not receive imaging-based diagnostics, resulting in inaccurate diagnoses[6]. As an adjunctive approach for risk stratification in TBI, cerebrospinal fluid (CSF) is effective; the invasiveness of the procedure severely limits its utility[7]. To prevent high-risk individuals from suffering lifelong TBI-

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