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Device Technologies and Biomedical Robotics

Undergraduate Advances in Device Technologies

Development of biosensor​ for early sepsis diagnosis

Saturday, October 26, 2024
8:45 AM - 9:00 AM EST
Location: Room 327

    Presenting Author(s)

  • John A. Pope, n/a

    Assistant Laboratory Technician
    LaBelle Labs at Grand Canyon University
    Surprise, Arizona, United States

  • Sarah Huynh, n/a

    Mechanical Engineering student with an emphasis in Aerospace
    Grand Canyon University
    Phoenix, Arizona, United States

    • Co-Author(s)

  • Alyson Schwartz (she/her/hers)

    Junior R&D Engineer
    Labellelabs, Grand Canyon University, Arizona, United States

  • Jeffrey T. LaBelle, PhD

    Professor
    Grand Canyon University
    Phoenix, Arizona, United States

  • Kentaro Hiraka, PhD

    Postdoctoral Fellow
    National Institute for Physiological Sciences, United States


Introduction:  Sepsis is a critical condition in which the human body begins to shut down due to a severe infection that often can remain undetected until it is too late. Sepsis is known to affect around 1.7 million people per year in the United States alone, with 350 000 of those affected later dying. The early detection of sepsis and the conditions leading up to it are therefore of utmost importance. An array of microneedles coated with gold nanoparticles and further modified with molecular recognition elements for biomarkers characteristic of pre-sepsis conditions can act as an effective early detection system for sepsis. The integration of the sensor into an adhesive patch will allow this device to be not only used by medical professionals, but also by patients themselves from the comfort of their own homes.
The following abstract outlines the extent of current progress with the early sepsis diagnosis biosensors. Electrochemical testing of the modified gold nanoparticles on sensors shows average detection of lactate and procalcitonin, two biomarkers indicative of sepsis.

Materials and

Methods:  Material:
The materials used are Zimmer Peacock Gold Electrodes, b2LOxS (Kentaro Hiraka et al., Tokyo University of Agriculture and Technology, Japan), Sodium L-lactate (Sigma-Aldrich, St Louis MO) , Procalcitonin (Thermo Fisher Scientific, Waltham MA), Anthraquinone-C6 NHS Ester (EMP Biotech, Germany), Phosphate Buffered Saline, Procalcitonin Binding Peptide (PCTBP3, Biomatik, Canada), Tween 20 (Sigma-Aldrich, St Louis MO), Graphene Oxide (Sigma-Aldrich, St Louis MO), Poly(ethylene Glycol) Diglycidyl (Sigma-Aldrich, St Louis MO), and Polyethylenimine (Sigma-Aldrich, St Louis MO).

Method:
Gold nanoparticles are synthesized and undergo two stages of modification. In the first stage, the particles are modified with a binding peptide for a biomarker associated with sepsis. In the second stage, the particles are modified with a redox probe to improve electrochemical detection for testing in solution. The modified gold nanoparticles are then combined with another enzyme able to detect a second biomarker associated with sepsis, creating an enzyme ink which is then applied to the gold screen-printed electrodes. The electrodes undergo a series of comprehensive electrochemical testing in solution with gradients of the targeted biomarkers. One bench starts with an increasing gradient of the first biomarker and the other bench starts with an increasing gradient of the second biomarker. Once the benches reach the 6th concentration of their respective biomarkers, the biomarkers are then swapped and cross-introduced to solution for each bench in increasing concentrations.

Results, Conclusions, and Discussions: Both benches showed strong detection of lactate and procalcitonin (PCT) at increasing concentrations of the individual biomarkers (Fig. 1a, and 1d respectively ). At lactate’s frequency, EIS resulted in a highly correlating best-fit line with R2 value of 0.9071. The best-fit line shows addition of increasing concentrations of lactate in PBS decreases the impedance of the solution. At PCT’s frequency, EIS resulted in a well correlating best-fit line with R2 value of 0.8555. The best-fit line shows addition of increasing concentrations of PCT in PBS increases the impedance of the solution.
With the addition of PCT concentrations to a constant lactate concentration, PCT did not have a strong detection at lactate’s frequency and had a good detection at its own frequency (middle two graphs). At lactate’s frequency, even though the correlation is poor, PCT still increases the impedance of the solution, that is why at its own frequency, the correlation is greatly increased.
With the addition of lactate concentrations to a constant PCT concentration, lactate was observed to decrease the solution’s impedance at its frequency (Fig. 1c). However, at PCT frequency, the mixed lactate-PCT solution increased in impedance (Fig. 1f). Both mixed solution graphs measured at PCT frequency (Fig. 1e, & 1f respectively) show a highly correlated, increasing trend of impedance as a function of increasing concentration, suggesting that PCT’s effect on the solution may outweigh lactate’s effect.

Figures 2 and 3 exhibit similar trends, suggesting that a peak at a more negative potential is indicative of the presence of lactate in solution and a peak at a more positive potential is indicative of procalcitonin. Figure 2 suggests that increasing concentrations of procalcitonin decreases peak current at more positive potentials.

In conclusion, it was found that both procalcitonin and lactate can be detected at their own frequencies using a screen-printed electrode, modified with gold nanoparticles and a redox probe. With further testing and experimentation, a compact, versatile, and efficient sensor for early sepsis detection can be a reality.

Acknowledgements (Optional):  The Flinn Foundation – Project Funding
Veronica Pramono – Laboratory Assistant, and Running Experiments
Praise Godspower – Laboratory Assistant, and Running Experiments