Comparison of GFAP and UCH-L1 Measurements from Two Prototype Assays: The Abbott i-STAT and ARCHITECT Assays

Abstract

Glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) may aid in the evaluation of traumatic brain injury (TBI). The objective of this analysis was to compare GFAP and UCH-L1 values measured using a handheld device compared with a core laboratory platform. We analyzed plasma samples from patients with TBI and healthy controls enrolled in the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) cohort study. GFAP and UCH-L1 were measured twice in each subject using prototype assays, first with the Abbott i-STAT TM handheld device, and second with the Abbott ARCHITECT â platform. We then quantified the agreement in biomarker values obtained using these two methods. GFAP and UCH-L1 were measured twice in 570 and 572 samples, respectively. GFAP values measured by the ARCHITECT platform (median 143.3 [interquartile range (IQR): 19.8-925.8] pg/mL) were higher than values measured by the i-STAT (median 116.0 [IQR: 9.2-856.5] pg/mL). GFAP values from the two platforms were strongly correlated ( p = 0.985). Similarly, UCH-L1 values measured by the ARCHITECT platform (median 163.9 [IQR: 82.5-412.4] pg/mL) were higher than values measured by the i-STAT (median 122.5 [IQR: 63.0-297.3] pg/mL). UCH-L1 values from the two platforms were strongly correlated ( p = 0.933). Passing-Bablok regression equations were developed to estimate the relationship between the two platforms, specifically to predict i-STAT values from the ARCHITECT platform. GFAP and UCH-L1 values measured using the prototype assays on the Abbott i-STAT and ARCHITECT platforms are strongly correlated and values from either platform may be converted to the other.

The Current State of Traumatic Brain Injury Biomarker Measurement Methods

“…The first clinical parameter is the choice of biomarker. GFAP and UCH-L1 are FDA cleared for assessing TBIs in the United States, and S100B is approved in Europe [23,24], but only 9 out of 25 devices described in the literature measured GFAP, 7 devices measured S100B, and not a single device measured UCH-L1. To improve the chances of device translation, the measured biomarkers should already have proven clinical utility.…”

“…To achieve testable prototypes as quickly as possible, TBI biomarker measurement device development should focus on multiplexing, assay evaluation with complex samples (serum, plasma, and/or whole blood), usability, and robustness. GFAP and UCH-L1 must be measured together in the United States to assess the need for a head CT scan [23], and panels of three or more biomarkers have been proposed [130,131]. Therefore, a TBI biomarker device is only clinically useful if it can measure at least two biomarkers simultaneously.…”

“…To capture the diversity of injured cell types, panels of biomarkers have been proposed to assess traumatic brain injuries [5,21,22]. As of June 2021, only GFAP and ubiquitin c-terminal hydrolase L1 (UCH-L1) are FDA cleared to aid in determining the need for evaluation with a head CT scan in the United States [23]. S100B is currently used for the same purpose in Europe and may result in a decrease in head CT utilization [24].…”

“…A positive result necessitates a head CT scan while a negative result rules out the need for a head CT [117]. TRACK-TBI (Transforming Research and Clinical Knowledge in Traumatic Brain Injury) studies using the i-STAT have recently concluded [17,23], and the device is set to be deployed in select hospitals in the United States by the end of 2021.…”

A Variable Height Microfluidic Device for Multiplexed Immunoassay Analysis of Traumatic Brain Injury Biomarkers

“…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. Glial fibrillary acidic protein (GFAP) and ubiquitin c-terminal hydrolase L1 (UCH-L1) are currently FDA approved to aid in determining the need for evaluation with a head CT scan [ 6 ]. However, TBI biomarker discovery and validation is an ongoing area of research, and multiple candidate molecules and proteins have been proposed [ 1 , 4 , 7 , 8 , 9 ].…”