Capture of the circulating Plasmodium falciparum biomarker HRP2 in a multiplexed format, via a wearable skin patch

Khai Tuck Lee, David A. Muller, Jacob W. Coffey, Kye J. Robinson, James S. McCarthy, Mark A. F. Kendall, Simon R. Corrie

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)

Abstract

Herein we demonstrate the use of a wearable device that can selectively capture two distinct circulating protein biomarkers (recombinant P. falciparum rPfHRP2 and total IgG) from the intradermal fluid of live mice in situ, for subsequent detection in vitro. The device comprises a microprojection array that, when applied to the skin, penetrates the outer skin layers to interface directly with intradermal fluid. Because of the complexity of the biological fluid being sampled, we investigated the effects of solution conditions on the attachment of capture antibodies, to optimize the assay detection limit both in vitro and on live mice. For detection of the target antigen diluted in 20% serum, immobilization conditions favoring high antibody surface density (low pH, low ionic strength) resulted in 100-fold greater sensitivity in comparison to standard conditions, yielding a detection limit equivalent to the plate enzyme-linked immunosorbent assay (ELISA). We also show that blocking the device surface to reduce nonspecific adsorption of target analyte and host proteins does not significantly change sensitivity. After injecting mice with rPfHRP2 via the tail vein, we compared analyte levels in both plasma and skin biopsies (cross-sectional area same as the microprojection array), observing that skin samples contained the equivalent of ∼8 μL of analyte-containing plasma. We then applied the arrays to mice, showing that surfaces coated with a high density of antibodies captured a significant amount of the rPfHRP2 target while the standard surface showed no capture in comparison to the negative control. Next, we applied a triplex device to both control and rPfHRP2-treated mice, simultaneously capturing rPfHRP2 and total IgG (as a positive control for skin penetration) in comparison to a negative control device. We conclude that such devices can be used to capture clinically relevant, circulating protein biomarkers of infectious disease via the skin, with potential applications as a minimally invasive and lab-free biomarker detection platform
Original languageEnglish
Pages (from-to)10474-10483
Number of pages10
JournalAnalytical Chemistry
Volume86
Issue number20
DOIs
Publication statusPublished - 21 Oct 2014
Externally publishedYes

Cite this

Lee, K. T., Muller, D. A., Coffey, J. W., Robinson, K. J., McCarthy, J. S., Kendall, M. A. F., & Corrie, S. R. (2014). Capture of the circulating Plasmodium falciparum biomarker HRP2 in a multiplexed format, via a wearable skin patch. Analytical Chemistry, 86(20), 10474-10483. https://doi.org/10.1021/ac5031682
Lee, Khai Tuck ; Muller, David A. ; Coffey, Jacob W. ; Robinson, Kye J. ; McCarthy, James S. ; Kendall, Mark A. F. ; Corrie, Simon R. / Capture of the circulating Plasmodium falciparum biomarker HRP2 in a multiplexed format, via a wearable skin patch. In: Analytical Chemistry. 2014 ; Vol. 86, No. 20. pp. 10474-10483.
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title = "Capture of the circulating Plasmodium falciparum biomarker HRP2 in a multiplexed format, via a wearable skin patch",
abstract = "Herein we demonstrate the use of a wearable device that can selectively capture two distinct circulating protein biomarkers (recombinant P. falciparum rPfHRP2 and total IgG) from the intradermal fluid of live mice in situ, for subsequent detection in vitro. The device comprises a microprojection array that, when applied to the skin, penetrates the outer skin layers to interface directly with intradermal fluid. Because of the complexity of the biological fluid being sampled, we investigated the effects of solution conditions on the attachment of capture antibodies, to optimize the assay detection limit both in vitro and on live mice. For detection of the target antigen diluted in 20{\%} serum, immobilization conditions favoring high antibody surface density (low pH, low ionic strength) resulted in 100-fold greater sensitivity in comparison to standard conditions, yielding a detection limit equivalent to the plate enzyme-linked immunosorbent assay (ELISA). We also show that blocking the device surface to reduce nonspecific adsorption of target analyte and host proteins does not significantly change sensitivity. After injecting mice with rPfHRP2 via the tail vein, we compared analyte levels in both plasma and skin biopsies (cross-sectional area same as the microprojection array), observing that skin samples contained the equivalent of ∼8 μL of analyte-containing plasma. We then applied the arrays to mice, showing that surfaces coated with a high density of antibodies captured a significant amount of the rPfHRP2 target while the standard surface showed no capture in comparison to the negative control. Next, we applied a triplex device to both control and rPfHRP2-treated mice, simultaneously capturing rPfHRP2 and total IgG (as a positive control for skin penetration) in comparison to a negative control device. We conclude that such devices can be used to capture clinically relevant, circulating protein biomarkers of infectious disease via the skin, with potential applications as a minimally invasive and lab-free biomarker detection platform",
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Lee, KT, Muller, DA, Coffey, JW, Robinson, KJ, McCarthy, JS, Kendall, MAF & Corrie, SR 2014, 'Capture of the circulating Plasmodium falciparum biomarker HRP2 in a multiplexed format, via a wearable skin patch', Analytical Chemistry, vol. 86, no. 20, pp. 10474-10483. https://doi.org/10.1021/ac5031682

Capture of the circulating Plasmodium falciparum biomarker HRP2 in a multiplexed format, via a wearable skin patch. / Lee, Khai Tuck; Muller, David A.; Coffey, Jacob W.; Robinson, Kye J.; McCarthy, James S.; Kendall, Mark A. F.; Corrie, Simon R.

In: Analytical Chemistry, Vol. 86, No. 20, 21.10.2014, p. 10474-10483.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Capture of the circulating Plasmodium falciparum biomarker HRP2 in a multiplexed format, via a wearable skin patch

AU - Lee, Khai Tuck

AU - Muller, David A.

AU - Coffey, Jacob W.

AU - Robinson, Kye J.

AU - McCarthy, James S.

AU - Kendall, Mark A. F.

AU - Corrie, Simon R.

PY - 2014/10/21

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N2 - Herein we demonstrate the use of a wearable device that can selectively capture two distinct circulating protein biomarkers (recombinant P. falciparum rPfHRP2 and total IgG) from the intradermal fluid of live mice in situ, for subsequent detection in vitro. The device comprises a microprojection array that, when applied to the skin, penetrates the outer skin layers to interface directly with intradermal fluid. Because of the complexity of the biological fluid being sampled, we investigated the effects of solution conditions on the attachment of capture antibodies, to optimize the assay detection limit both in vitro and on live mice. For detection of the target antigen diluted in 20% serum, immobilization conditions favoring high antibody surface density (low pH, low ionic strength) resulted in 100-fold greater sensitivity in comparison to standard conditions, yielding a detection limit equivalent to the plate enzyme-linked immunosorbent assay (ELISA). We also show that blocking the device surface to reduce nonspecific adsorption of target analyte and host proteins does not significantly change sensitivity. After injecting mice with rPfHRP2 via the tail vein, we compared analyte levels in both plasma and skin biopsies (cross-sectional area same as the microprojection array), observing that skin samples contained the equivalent of ∼8 μL of analyte-containing plasma. We then applied the arrays to mice, showing that surfaces coated with a high density of antibodies captured a significant amount of the rPfHRP2 target while the standard surface showed no capture in comparison to the negative control. Next, we applied a triplex device to both control and rPfHRP2-treated mice, simultaneously capturing rPfHRP2 and total IgG (as a positive control for skin penetration) in comparison to a negative control device. We conclude that such devices can be used to capture clinically relevant, circulating protein biomarkers of infectious disease via the skin, with potential applications as a minimally invasive and lab-free biomarker detection platform

AB - Herein we demonstrate the use of a wearable device that can selectively capture two distinct circulating protein biomarkers (recombinant P. falciparum rPfHRP2 and total IgG) from the intradermal fluid of live mice in situ, for subsequent detection in vitro. The device comprises a microprojection array that, when applied to the skin, penetrates the outer skin layers to interface directly with intradermal fluid. Because of the complexity of the biological fluid being sampled, we investigated the effects of solution conditions on the attachment of capture antibodies, to optimize the assay detection limit both in vitro and on live mice. For detection of the target antigen diluted in 20% serum, immobilization conditions favoring high antibody surface density (low pH, low ionic strength) resulted in 100-fold greater sensitivity in comparison to standard conditions, yielding a detection limit equivalent to the plate enzyme-linked immunosorbent assay (ELISA). We also show that blocking the device surface to reduce nonspecific adsorption of target analyte and host proteins does not significantly change sensitivity. After injecting mice with rPfHRP2 via the tail vein, we compared analyte levels in both plasma and skin biopsies (cross-sectional area same as the microprojection array), observing that skin samples contained the equivalent of ∼8 μL of analyte-containing plasma. We then applied the arrays to mice, showing that surfaces coated with a high density of antibodies captured a significant amount of the rPfHRP2 target while the standard surface showed no capture in comparison to the negative control. Next, we applied a triplex device to both control and rPfHRP2-treated mice, simultaneously capturing rPfHRP2 and total IgG (as a positive control for skin penetration) in comparison to a negative control device. We conclude that such devices can be used to capture clinically relevant, circulating protein biomarkers of infectious disease via the skin, with potential applications as a minimally invasive and lab-free biomarker detection platform

U2 - 10.1021/ac5031682

DO - 10.1021/ac5031682

M3 - Article

VL - 86

SP - 10474

EP - 10483

JO - Analytical Chemistry

JF - Analytical Chemistry

SN - 0003-2700

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ER -