Abstract
A major impediment to improving the treatment of concussion is our current inability to identify patients that will experience persistent problems after the injury. Recently, brain-derived exosomes, which cross the blood-brain barrier and circulate following injury, have shown great potential as a noninvasive biomarker of brain recovery. However, clinical use of exosomes has been constrained by their small size (30–100 nm) and the extensive sample preparation (>24 hr) needed for traditional exosome measurements. To address these challenges, we developed a smartphone-enabled optofluidic platform to measure brain-derived exosomes. Sample-to-answer on our chip is 1 hour, 10x faster than conventional techniques. The key innovation is an optofluidic device that can detect enzyme amplified exosome biomarkers, and is read out using a smartphone camera. Using this approach, we detected and profiled GluR2+ exosomes in the post-injury state using both in vitro and murine models of concussion.
Highlights
Mild traumatic brain injury, i.e. concussion, occurs in 1.7–2 million people each year[1,2]
There is a great interest in developing biomarkers for both the detection and treatment of concussion, the molecular biomarkers are difficult to detect for clinical use in Mild traumatic brain injury (mTBI) because the blood-brain barrier (BBB) remains intact after injury[7,8,9]
Using two different models of mTBI – controlled cortical impact (CCI)[27] and exposure to a controlled shock wave28 – we demonstrated that our assay could detect an increased level of glutamate receptor 2 (GluR2)+exosomes following mTBI (Fig. 6a)
Summary
Our smartphone-based mTBI diagnostics, μMED, offers rapid, portable, and cost effective technology that can monitor mTBI and prognose secondary brain injury, which are otherwise extremely expensive (brain MRI ~$5000) and hard to predict. Extracting exosomes that originate in a specific target organ from a blood sample presents an exciting diagnostic potential for additional diseases beyond TBI. The specificity of these tests will rely heavily on the identification of exosome surface markers that are unique to the relevant tissue or cell type. Due to the modular nature of our chip, it can be further improved to profile multiple exosomal biomarkers at once on the same chip resulting in an increasingly specific and detailed picture of the recovering brain[7] These features allow the μMED chip to be a powerful tool suitable for practical use in the clinic
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