(610e) A Variable Height Microfluidic Device for Traumatic Brain Injury Diagnosis and Prognosis (Industry Candidate)

Traumatic brain injury (TBI) causes significant morbidity and mortality globally partially due to ineffective diagnostic and treatment methods [1]. Assessment of TBI injuries is typically done through neurological examination and neuroimaging techniques. While these methods are capable of identifying direct tissue damage to the brain, they cannot assess the secondary damage stemming from the initial injury. The primary tissue damage sets off a cascade of secondary injuries, such as neuronal cell death, blood brain barrier breakdown, edema, and upregulation of inflammatory markers [1]. Protein biomarkers have been proposed as a way of monitoring the progression of secondary TBI injury and of providing more sensitive diagnostic measures when used in conjunction with imaging and physical examination. FDA approved biomarkers, glial fibrillary acidic protein (GFAP) and ubiquitin c-terminal hydrolase L1 (UCH-L1), can currently only be measured in a hospital laboratory [2].

To make TBI biomarker data actionable in field and pre-hospital settings, we are developing a glass microfluidic device for protein quantification via bead-based immunoassay. The device consists of a single channel with a variable height profile fabricated by slowly lowering a glass wafer into hydrofluoric acid [3]. The device is capable of capturing and separating beads with diameters ranging from 1.5 to 4 µm (Figure 1B). We also developed bead-based QLISAs (quantum dot-linked immunosorbent assay) for GFAP, interleukin-6 (IL-6), and interleukin-8 (IL-8) by conjugating appropriate antibodies to 2.8, 4.5, and 1 µm diameter beads, respectively. The GFAP QLISA is capable of quantifying GFAP in the range of 0.01-50 ng/mL. We used the variable height device to capture the 2.8 µm GFAP assay beads and analyze the fluorescence intensity of buffer samples spiked with varying GFAP concentrations (Figure 1A).

The variable height device is an adaptable microfluidic platform with the potential to quantify multiple biomarkers simultaneously. By using different sized beads for the GFAP, IL-6, and IL-8 immunoassays, the microfluidic platform can analyze a panel of TBI biomarkers [4]. By changing out the bead size and antibodies used for each immunoassay, the variable height device is able to keep pace with the developing field of TBI biomarker discovery and validation. Once a fully point-of-care platform is realized with portable optics, our device has the potential to make TBI biomarker data actionable in both field and hospital settings.

[1] Loane, D. J., & Faden, A. I. (2010). Neuroprotection for traumatic brain injury: translational challenges and emerging therapeutic strategies. Trends in pharmacological sciences, 31(12), 596-604.

[2] Papa, L., et. al. (2016). Time course and diagnostic accuracy of glial and neuronal blood biomarkers GFAP and UCH-L1 in a large cohort of trauma patients with and without mild traumatic brain injury. JAMA neurology, 73(5), 551-560.

[3] de Beer, M. (2020). Advances in additive manufacturing and microfluidics. (Doctoral dissertation, University of Michigan, Ann Arbor, MI, USA).

[4] Morganti-Kossman, M. C., et. al. (1997). Production of cytokines following brain injury: beneficial and deleterious for the damaged tissue. Molecular psychiatry, 2(2), 133-136.