Multi-biomarker detection following traumatic brain injury

Brittney A. Cardinell, Caroline P. Addington, Sarah Stabenfeldt, Jeffrey LaBelle

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The Centers for Disease Control and Prevention estimates almost two million traumatic brain injuries (TBIs) occur annually in the U.S., resulting in nearly $80 billion of economic burden. Despite its prevalence, current TBI diagnosis methods mainly rely on cognitive assessments vulnerable to subjective interpretation, thus highlighting the critical need to develop effective unbiased diagnostic methods. The presented study aims to assess the feasibility of a rapid multianalyte TBI blood diagnostic. Specifically, two electrochemical impedance techniques were used to evaluate four biomarkers: glial fibrillary acidic protein, neuron specific enolase (NSE), S-100β, and tumor necrosis factor-α. First, these biomarkers were characterized in purified solutions (detection limit, DL = 2–5 pg/mL), then verified in spiked whole blood and plasma solutions (90% whole blood DL = 14–67 pg/mL). Finally, detection of two of these biomarkers was validated in a controlled cortical impact model of TBI in rats, where a statistical difference between NSE and S-100β concentrations differed several days postinjury (p = 0.02 and p = 0.06, respectively). A statistical difference between mild and moderate injury was found at the various time points. The proposed diagnostic method enabled preliminary quantification of TBI-relevant biomarkers in complex media without the use of expensive electrode coatings or membranes. Collectively, these data demonstrate the feasibility of using electrochemical impedance techniques to rapidly detect TBI biomarkers and lay the groundwork for development of a novel method for quantitative diagnostics of TBI.

Original languageEnglish (US)
Pages (from-to)193-206
Number of pages14
JournalCritical Reviews in Biomedical Engineering
Volume47
Issue number3
DOIs
StatePublished - Jan 1 2019

Fingerprint

Biomarkers
Brain
Blood
Neurons
Disease control
Rats
Proteins
Membranes
Plasmas
Coatings
Economics
Electrodes

Keywords

  • Electrochemical impedance spectroscopy
  • Glial fibrillary acidic protein
  • Impedance-time
  • Neuron specific enolase
  • S-100β
  • Traumatic brain injury
  • Tumor necrosis factor alpha

ASJC Scopus subject areas

  • Biomedical Engineering

Cite this

Multi-biomarker detection following traumatic brain injury. / Cardinell, Brittney A.; Addington, Caroline P.; Stabenfeldt, Sarah; LaBelle, Jeffrey.

In: Critical Reviews in Biomedical Engineering, Vol. 47, No. 3, 01.01.2019, p. 193-206.

Research output: Contribution to journalArticle

Cardinell, Brittney A. ; Addington, Caroline P. ; Stabenfeldt, Sarah ; LaBelle, Jeffrey. / Multi-biomarker detection following traumatic brain injury. In: Critical Reviews in Biomedical Engineering. 2019 ; Vol. 47, No. 3. pp. 193-206.
@article{b45e212c83dc4edd84fab39fb299099e,
title = "Multi-biomarker detection following traumatic brain injury",
abstract = "The Centers for Disease Control and Prevention estimates almost two million traumatic brain injuries (TBIs) occur annually in the U.S., resulting in nearly $80 billion of economic burden. Despite its prevalence, current TBI diagnosis methods mainly rely on cognitive assessments vulnerable to subjective interpretation, thus highlighting the critical need to develop effective unbiased diagnostic methods. The presented study aims to assess the feasibility of a rapid multianalyte TBI blood diagnostic. Specifically, two electrochemical impedance techniques were used to evaluate four biomarkers: glial fibrillary acidic protein, neuron specific enolase (NSE), S-100β, and tumor necrosis factor-α. First, these biomarkers were characterized in purified solutions (detection limit, DL = 2–5 pg/mL), then verified in spiked whole blood and plasma solutions (90{\%} whole blood DL = 14–67 pg/mL). Finally, detection of two of these biomarkers was validated in a controlled cortical impact model of TBI in rats, where a statistical difference between NSE and S-100β concentrations differed several days postinjury (p = 0.02 and p = 0.06, respectively). A statistical difference between mild and moderate injury was found at the various time points. The proposed diagnostic method enabled preliminary quantification of TBI-relevant biomarkers in complex media without the use of expensive electrode coatings or membranes. Collectively, these data demonstrate the feasibility of using electrochemical impedance techniques to rapidly detect TBI biomarkers and lay the groundwork for development of a novel method for quantitative diagnostics of TBI.",
keywords = "Electrochemical impedance spectroscopy, Glial fibrillary acidic protein, Impedance-time, Neuron specific enolase, S-100β, Traumatic brain injury, Tumor necrosis factor alpha",
author = "Cardinell, {Brittney A.} and Addington, {Caroline P.} and Sarah Stabenfeldt and Jeffrey LaBelle",
year = "2019",
month = "1",
day = "1",
doi = "10.1615/CritRevBiomedEng.2019026108",
language = "English (US)",
volume = "47",
pages = "193--206",
journal = "Critical Reviews in Biomedical Engineering",
issn = "0278-940X",
publisher = "Begell House Inc.",
number = "3",

}

TY - JOUR

T1 - Multi-biomarker detection following traumatic brain injury

AU - Cardinell, Brittney A.

AU - Addington, Caroline P.

AU - Stabenfeldt, Sarah

AU - LaBelle, Jeffrey

PY - 2019/1/1

Y1 - 2019/1/1

N2 - The Centers for Disease Control and Prevention estimates almost two million traumatic brain injuries (TBIs) occur annually in the U.S., resulting in nearly $80 billion of economic burden. Despite its prevalence, current TBI diagnosis methods mainly rely on cognitive assessments vulnerable to subjective interpretation, thus highlighting the critical need to develop effective unbiased diagnostic methods. The presented study aims to assess the feasibility of a rapid multianalyte TBI blood diagnostic. Specifically, two electrochemical impedance techniques were used to evaluate four biomarkers: glial fibrillary acidic protein, neuron specific enolase (NSE), S-100β, and tumor necrosis factor-α. First, these biomarkers were characterized in purified solutions (detection limit, DL = 2–5 pg/mL), then verified in spiked whole blood and plasma solutions (90% whole blood DL = 14–67 pg/mL). Finally, detection of two of these biomarkers was validated in a controlled cortical impact model of TBI in rats, where a statistical difference between NSE and S-100β concentrations differed several days postinjury (p = 0.02 and p = 0.06, respectively). A statistical difference between mild and moderate injury was found at the various time points. The proposed diagnostic method enabled preliminary quantification of TBI-relevant biomarkers in complex media without the use of expensive electrode coatings or membranes. Collectively, these data demonstrate the feasibility of using electrochemical impedance techniques to rapidly detect TBI biomarkers and lay the groundwork for development of a novel method for quantitative diagnostics of TBI.

AB - The Centers for Disease Control and Prevention estimates almost two million traumatic brain injuries (TBIs) occur annually in the U.S., resulting in nearly $80 billion of economic burden. Despite its prevalence, current TBI diagnosis methods mainly rely on cognitive assessments vulnerable to subjective interpretation, thus highlighting the critical need to develop effective unbiased diagnostic methods. The presented study aims to assess the feasibility of a rapid multianalyte TBI blood diagnostic. Specifically, two electrochemical impedance techniques were used to evaluate four biomarkers: glial fibrillary acidic protein, neuron specific enolase (NSE), S-100β, and tumor necrosis factor-α. First, these biomarkers were characterized in purified solutions (detection limit, DL = 2–5 pg/mL), then verified in spiked whole blood and plasma solutions (90% whole blood DL = 14–67 pg/mL). Finally, detection of two of these biomarkers was validated in a controlled cortical impact model of TBI in rats, where a statistical difference between NSE and S-100β concentrations differed several days postinjury (p = 0.02 and p = 0.06, respectively). A statistical difference between mild and moderate injury was found at the various time points. The proposed diagnostic method enabled preliminary quantification of TBI-relevant biomarkers in complex media without the use of expensive electrode coatings or membranes. Collectively, these data demonstrate the feasibility of using electrochemical impedance techniques to rapidly detect TBI biomarkers and lay the groundwork for development of a novel method for quantitative diagnostics of TBI.

KW - Electrochemical impedance spectroscopy

KW - Glial fibrillary acidic protein

KW - Impedance-time

KW - Neuron specific enolase

KW - S-100β

KW - Traumatic brain injury

KW - Tumor necrosis factor alpha

UR - http://www.scopus.com/inward/record.url?scp=85067994789&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067994789&partnerID=8YFLogxK

U2 - 10.1615/CritRevBiomedEng.2019026108

DO - 10.1615/CritRevBiomedEng.2019026108

M3 - Article

VL - 47

SP - 193

EP - 206

JO - Critical Reviews in Biomedical Engineering

JF - Critical Reviews in Biomedical Engineering

SN - 0278-940X

IS - 3

ER -