Approaching single molecule sensing: Predictive sweat sensor design for ultra-low limits of detection

Jonathan Harris, Justin Bickford, Pak Cho, Matthew Coppock, Mikella Farrell, Ellen Holthoff, Erin L Ratcliff

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Sweat provides direct information of the real-time emotional and cognitive state of the subject, with applications ranging from situational awareness and mission effectiveness of armed forces to disease diagnosis for clinicians. Development of a broad class of human performance monitoring devices to quantify sweat biomarkers necessitates non-invasive, real-time monitoring of ultra-low concentrations (μM to fM) of hormones, proteins, and neurotransmitters. Field effect transistors are the predominant sensor approach whereby the gate electrode is modified with a selective bio-recognition element (BRE). However, FETs have diminished sensitivity in high ionic strength environments associated with sweat. Alternatively, BRE-modified photonic integrated circuits (PICs) have high sensitivity in high ionic strength fluids, low cost at the manufacturing scale, and enable a number of novel device concepts to achieve ultra-low levels of detection. One major technological challenge is to predict the limit of detection (LoD), or sensor response function, for a particular PIC geometry in a microfluidic chamber. LoD is highly dependent on analytic capture efficiency, fluid dynamics and affinity, analyte/light interaction, and analyte concentration. This work presents finite element simulations to emulate microfluidic BRE sweat sensors and provide a predictive limit of detection for different sensing structures or elements. Specifically, the optimum mass transfer and kinetics for sensing approaching single molecule detection is discussed, including flow characteristics, biomarker size, adsorption and desorption kinetics, and sensor geometry. Key metrics include capture efficiency (molecules being captured over molecules entering channel), time to reach steady state, and temporal adsorption site occupancy to predict PIC system LoD. It is found that these systems are kinetically controlled, with capture efficiencies remaining below 1% even for kads/kdes ratios of 1010. The need for adsorption kinetics measured for flow systems instead of stationary fluid systems is stressed, as these parameters are what need to be optimized to greatly increase analyte capture.

Original languageEnglish (US)
Title of host publicationChemical, Biological, Radiological, Nuclear, and Explosives (CBRNE) Sensing XX
EditorsJason A. Guicheteau, Chris R. Howle
PublisherSPIE
ISBN (Electronic)9781510626850
DOIs
StatePublished - Jan 1 2019
EventChemical, Biological, Radiological, Nuclear, and Explosives (CBRNE) Sensing XX 2019 - Baltimore, United States
Duration: Apr 15 2019Apr 17 2019

Publication series

NameProceedings of SPIE - The International Society for Optical Engineering
Volume11010
ISSN (Print)0277-786X
ISSN (Electronic)1996-756X

Conference

ConferenceChemical, Biological, Radiological, Nuclear, and Explosives (CBRNE) Sensing XX 2019
CountryUnited States
CityBaltimore
Period4/15/194/17/19

Fingerprint

sweat
Sensing
Photonics
Photonic Integrated Circuits
Integrated circuits
Sensor
Molecules
sensors
Sensors
Biomarkers
Field effect transistors
Ionic strength
Microfluidics
Adsorption
Kinetics
molecules
integrated circuits
Fluids
Geometry
Monitoring

Keywords

  • Bio-recognition elements
  • Biosensing
  • Finite element simulations
  • Fluid dynamics
  • Microfluidics
  • Photonic integrated circuits
  • Photonic sensing
  • Sweat sensing

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Condensed Matter Physics
  • Computer Science Applications
  • Applied Mathematics
  • Electrical and Electronic Engineering

Cite this

Harris, J., Bickford, J., Cho, P., Coppock, M., Farrell, M., Holthoff, E., & Ratcliff, E. L. (2019). Approaching single molecule sensing: Predictive sweat sensor design for ultra-low limits of detection. In J. A. Guicheteau, & C. R. Howle (Eds.), Chemical, Biological, Radiological, Nuclear, and Explosives (CBRNE) Sensing XX [110100F] (Proceedings of SPIE - The International Society for Optical Engineering; Vol. 11010). SPIE. https://doi.org/10.1117/12.2518543

Approaching single molecule sensing : Predictive sweat sensor design for ultra-low limits of detection. / Harris, Jonathan; Bickford, Justin; Cho, Pak; Coppock, Matthew; Farrell, Mikella; Holthoff, Ellen; Ratcliff, Erin L.

Chemical, Biological, Radiological, Nuclear, and Explosives (CBRNE) Sensing XX. ed. / Jason A. Guicheteau; Chris R. Howle. SPIE, 2019. 110100F (Proceedings of SPIE - The International Society for Optical Engineering; Vol. 11010).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Harris, J, Bickford, J, Cho, P, Coppock, M, Farrell, M, Holthoff, E & Ratcliff, EL 2019, Approaching single molecule sensing: Predictive sweat sensor design for ultra-low limits of detection. in JA Guicheteau & CR Howle (eds), Chemical, Biological, Radiological, Nuclear, and Explosives (CBRNE) Sensing XX., 110100F, Proceedings of SPIE - The International Society for Optical Engineering, vol. 11010, SPIE, Chemical, Biological, Radiological, Nuclear, and Explosives (CBRNE) Sensing XX 2019, Baltimore, United States, 4/15/19. https://doi.org/10.1117/12.2518543
Harris J, Bickford J, Cho P, Coppock M, Farrell M, Holthoff E et al. Approaching single molecule sensing: Predictive sweat sensor design for ultra-low limits of detection. In Guicheteau JA, Howle CR, editors, Chemical, Biological, Radiological, Nuclear, and Explosives (CBRNE) Sensing XX. SPIE. 2019. 110100F. (Proceedings of SPIE - The International Society for Optical Engineering). https://doi.org/10.1117/12.2518543
Harris, Jonathan ; Bickford, Justin ; Cho, Pak ; Coppock, Matthew ; Farrell, Mikella ; Holthoff, Ellen ; Ratcliff, Erin L. / Approaching single molecule sensing : Predictive sweat sensor design for ultra-low limits of detection. Chemical, Biological, Radiological, Nuclear, and Explosives (CBRNE) Sensing XX. editor / Jason A. Guicheteau ; Chris R. Howle. SPIE, 2019. (Proceedings of SPIE - The International Society for Optical Engineering).
@inproceedings{404e81d5ccbe4a8988f61879ff30a85c,
title = "Approaching single molecule sensing: Predictive sweat sensor design for ultra-low limits of detection",
abstract = "Sweat provides direct information of the real-time emotional and cognitive state of the subject, with applications ranging from situational awareness and mission effectiveness of armed forces to disease diagnosis for clinicians. Development of a broad class of human performance monitoring devices to quantify sweat biomarkers necessitates non-invasive, real-time monitoring of ultra-low concentrations (μM to fM) of hormones, proteins, and neurotransmitters. Field effect transistors are the predominant sensor approach whereby the gate electrode is modified with a selective bio-recognition element (BRE). However, FETs have diminished sensitivity in high ionic strength environments associated with sweat. Alternatively, BRE-modified photonic integrated circuits (PICs) have high sensitivity in high ionic strength fluids, low cost at the manufacturing scale, and enable a number of novel device concepts to achieve ultra-low levels of detection. One major technological challenge is to predict the limit of detection (LoD), or sensor response function, for a particular PIC geometry in a microfluidic chamber. LoD is highly dependent on analytic capture efficiency, fluid dynamics and affinity, analyte/light interaction, and analyte concentration. This work presents finite element simulations to emulate microfluidic BRE sweat sensors and provide a predictive limit of detection for different sensing structures or elements. Specifically, the optimum mass transfer and kinetics for sensing approaching single molecule detection is discussed, including flow characteristics, biomarker size, adsorption and desorption kinetics, and sensor geometry. Key metrics include capture efficiency (molecules being captured over molecules entering channel), time to reach steady state, and temporal adsorption site occupancy to predict PIC system LoD. It is found that these systems are kinetically controlled, with capture efficiencies remaining below 1{\%} even for kads/kdes ratios of 1010. The need for adsorption kinetics measured for flow systems instead of stationary fluid systems is stressed, as these parameters are what need to be optimized to greatly increase analyte capture.",
keywords = "Bio-recognition elements, Biosensing, Finite element simulations, Fluid dynamics, Microfluidics, Photonic integrated circuits, Photonic sensing, Sweat sensing",
author = "Jonathan Harris and Justin Bickford and Pak Cho and Matthew Coppock and Mikella Farrell and Ellen Holthoff and Ratcliff, {Erin L}",
year = "2019",
month = "1",
day = "1",
doi = "10.1117/12.2518543",
language = "English (US)",
series = "Proceedings of SPIE - The International Society for Optical Engineering",
publisher = "SPIE",
editor = "Guicheteau, {Jason A.} and Howle, {Chris R.}",
booktitle = "Chemical, Biological, Radiological, Nuclear, and Explosives (CBRNE) Sensing XX",

}

TY - GEN

T1 - Approaching single molecule sensing

T2 - Predictive sweat sensor design for ultra-low limits of detection

AU - Harris, Jonathan

AU - Bickford, Justin

AU - Cho, Pak

AU - Coppock, Matthew

AU - Farrell, Mikella

AU - Holthoff, Ellen

AU - Ratcliff, Erin L

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Sweat provides direct information of the real-time emotional and cognitive state of the subject, with applications ranging from situational awareness and mission effectiveness of armed forces to disease diagnosis for clinicians. Development of a broad class of human performance monitoring devices to quantify sweat biomarkers necessitates non-invasive, real-time monitoring of ultra-low concentrations (μM to fM) of hormones, proteins, and neurotransmitters. Field effect transistors are the predominant sensor approach whereby the gate electrode is modified with a selective bio-recognition element (BRE). However, FETs have diminished sensitivity in high ionic strength environments associated with sweat. Alternatively, BRE-modified photonic integrated circuits (PICs) have high sensitivity in high ionic strength fluids, low cost at the manufacturing scale, and enable a number of novel device concepts to achieve ultra-low levels of detection. One major technological challenge is to predict the limit of detection (LoD), or sensor response function, for a particular PIC geometry in a microfluidic chamber. LoD is highly dependent on analytic capture efficiency, fluid dynamics and affinity, analyte/light interaction, and analyte concentration. This work presents finite element simulations to emulate microfluidic BRE sweat sensors and provide a predictive limit of detection for different sensing structures or elements. Specifically, the optimum mass transfer and kinetics for sensing approaching single molecule detection is discussed, including flow characteristics, biomarker size, adsorption and desorption kinetics, and sensor geometry. Key metrics include capture efficiency (molecules being captured over molecules entering channel), time to reach steady state, and temporal adsorption site occupancy to predict PIC system LoD. It is found that these systems are kinetically controlled, with capture efficiencies remaining below 1% even for kads/kdes ratios of 1010. The need for adsorption kinetics measured for flow systems instead of stationary fluid systems is stressed, as these parameters are what need to be optimized to greatly increase analyte capture.

AB - Sweat provides direct information of the real-time emotional and cognitive state of the subject, with applications ranging from situational awareness and mission effectiveness of armed forces to disease diagnosis for clinicians. Development of a broad class of human performance monitoring devices to quantify sweat biomarkers necessitates non-invasive, real-time monitoring of ultra-low concentrations (μM to fM) of hormones, proteins, and neurotransmitters. Field effect transistors are the predominant sensor approach whereby the gate electrode is modified with a selective bio-recognition element (BRE). However, FETs have diminished sensitivity in high ionic strength environments associated with sweat. Alternatively, BRE-modified photonic integrated circuits (PICs) have high sensitivity in high ionic strength fluids, low cost at the manufacturing scale, and enable a number of novel device concepts to achieve ultra-low levels of detection. One major technological challenge is to predict the limit of detection (LoD), or sensor response function, for a particular PIC geometry in a microfluidic chamber. LoD is highly dependent on analytic capture efficiency, fluid dynamics and affinity, analyte/light interaction, and analyte concentration. This work presents finite element simulations to emulate microfluidic BRE sweat sensors and provide a predictive limit of detection for different sensing structures or elements. Specifically, the optimum mass transfer and kinetics for sensing approaching single molecule detection is discussed, including flow characteristics, biomarker size, adsorption and desorption kinetics, and sensor geometry. Key metrics include capture efficiency (molecules being captured over molecules entering channel), time to reach steady state, and temporal adsorption site occupancy to predict PIC system LoD. It is found that these systems are kinetically controlled, with capture efficiencies remaining below 1% even for kads/kdes ratios of 1010. The need for adsorption kinetics measured for flow systems instead of stationary fluid systems is stressed, as these parameters are what need to be optimized to greatly increase analyte capture.

KW - Bio-recognition elements

KW - Biosensing

KW - Finite element simulations

KW - Fluid dynamics

KW - Microfluidics

KW - Photonic integrated circuits

KW - Photonic sensing

KW - Sweat sensing

UR - http://www.scopus.com/inward/record.url?scp=85072388164&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072388164&partnerID=8YFLogxK

U2 - 10.1117/12.2518543

DO - 10.1117/12.2518543

M3 - Conference contribution

AN - SCOPUS:85072388164

T3 - Proceedings of SPIE - The International Society for Optical Engineering

BT - Chemical, Biological, Radiological, Nuclear, and Explosives (CBRNE) Sensing XX

A2 - Guicheteau, Jason A.

A2 - Howle, Chris R.

PB - SPIE

ER -