Multiplex diagnosis of viral infectious diseases (AIDS, hepatitis C, and hepatitis A) based on point of care lateral flow assay using engineered proteinticles

Jong Hwan Lee, Hyuk Seong Seo, Jung Hyuk Kwon, Hee Tae Kim, Koo Chul Kwon, Sang Jun Sim, Young Joo Cha, Jeewon Lee

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Lateral flow assay (LFA) is an attractive method for rapid, simple, and cost-effective point of care diagnosis. For LFA-based multiplex diagnosis of three viral intractable diseases (acquired immune deficiency syndrome and hepatitis C and A), here we developed proteinticle-based 7 different 3D probes that display different viral antigens on their surface, which were synthesized in Escherichia coli by self-assembly of human ferritin heavy chain that was already engineered by genetically linking viral antigens to its C-terminus. Each of the three test lines on LFA strip contains the proteinticle probes to detect disease-specific anti-viral antibodies. Compared to peptide probes, the proteinticle probes were evidently more sensitive, and the proteinticle probe-based LFA successfully diagnosed all the 20 patient sera per each disease without a false negative signal, whereas the diagnostic sensitivities in the peptide probe-based LFAs were 65-90%. Duplex and triplex assays performed with randomly mixed patient sera gave only true positive signals for all the 20 serum mixtures without any false positive signals, indicating 100% sensitivity and 100% specificity. It seems that on the proteinticle surface the antigenic peptides have homogeneous orientation and conformation without inter-peptide clustering and hence lead to the enhanced diagnostic performance with solving the problems of traditional diagnostic probes. Although the multiplex diagnosis of three viral diseases above was demonstrated as proof-of-concept here, the proposed LFA system can be applied to multiplex point of care diagnosis of other intractable diseases.

Original languageEnglish
Pages (from-to)213-225
Number of pages13
JournalBiosensors and Bioelectronics
Volume69
DOIs
Publication statusPublished - 2015 Jul 5

Fingerprint

Point-of-Care Systems
Hepatitis A
Virus Diseases
Hepatitis C
Communicable Diseases
Assays
Acquired Immunodeficiency Syndrome
Peptides
Viral Antigens
Serum
Viral Antibodies
Apoferritins
Antigens
Cluster Analysis
Anti-Idiotypic Antibodies
Escherichia coli
Costs and Cost Analysis
Sensitivity and Specificity
Antibodies
Crystal orientation

Keywords

  • Infectious diseases
  • Lateral flow assay
  • Multiplex diagnosis
  • Proteinticles
  • Surface engineering

ASJC Scopus subject areas

  • Biophysics
  • Biomedical Engineering
  • Biotechnology
  • Electrochemistry

Cite this

Multiplex diagnosis of viral infectious diseases (AIDS, hepatitis C, and hepatitis A) based on point of care lateral flow assay using engineered proteinticles. / Lee, Jong Hwan; Seo, Hyuk Seong; Kwon, Jung Hyuk; Kim, Hee Tae; Kwon, Koo Chul; Sim, Sang Jun; Cha, Young Joo; Lee, Jeewon.

In: Biosensors and Bioelectronics, Vol. 69, 05.07.2015, p. 213-225.

Research output: Contribution to journalArticle

@article{37a47c35f3c8425399060c8e1a13e304,
title = "Multiplex diagnosis of viral infectious diseases (AIDS, hepatitis C, and hepatitis A) based on point of care lateral flow assay using engineered proteinticles",
abstract = "Lateral flow assay (LFA) is an attractive method for rapid, simple, and cost-effective point of care diagnosis. For LFA-based multiplex diagnosis of three viral intractable diseases (acquired immune deficiency syndrome and hepatitis C and A), here we developed proteinticle-based 7 different 3D probes that display different viral antigens on their surface, which were synthesized in Escherichia coli by self-assembly of human ferritin heavy chain that was already engineered by genetically linking viral antigens to its C-terminus. Each of the three test lines on LFA strip contains the proteinticle probes to detect disease-specific anti-viral antibodies. Compared to peptide probes, the proteinticle probes were evidently more sensitive, and the proteinticle probe-based LFA successfully diagnosed all the 20 patient sera per each disease without a false negative signal, whereas the diagnostic sensitivities in the peptide probe-based LFAs were 65-90{\%}. Duplex and triplex assays performed with randomly mixed patient sera gave only true positive signals for all the 20 serum mixtures without any false positive signals, indicating 100{\%} sensitivity and 100{\%} specificity. It seems that on the proteinticle surface the antigenic peptides have homogeneous orientation and conformation without inter-peptide clustering and hence lead to the enhanced diagnostic performance with solving the problems of traditional diagnostic probes. Although the multiplex diagnosis of three viral diseases above was demonstrated as proof-of-concept here, the proposed LFA system can be applied to multiplex point of care diagnosis of other intractable diseases.",
keywords = "Infectious diseases, Lateral flow assay, Multiplex diagnosis, Proteinticles, Surface engineering",
author = "Lee, {Jong Hwan} and Seo, {Hyuk Seong} and Kwon, {Jung Hyuk} and Kim, {Hee Tae} and Kwon, {Koo Chul} and Sim, {Sang Jun} and Cha, {Young Joo} and Jeewon Lee",
year = "2015",
month = "7",
day = "5",
doi = "10.1016/j.bios.2015.02.033",
language = "English",
volume = "69",
pages = "213--225",
journal = "Biosensors",
issn = "0956-5663",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Multiplex diagnosis of viral infectious diseases (AIDS, hepatitis C, and hepatitis A) based on point of care lateral flow assay using engineered proteinticles

AU - Lee, Jong Hwan

AU - Seo, Hyuk Seong

AU - Kwon, Jung Hyuk

AU - Kim, Hee Tae

AU - Kwon, Koo Chul

AU - Sim, Sang Jun

AU - Cha, Young Joo

AU - Lee, Jeewon

PY - 2015/7/5

Y1 - 2015/7/5

N2 - Lateral flow assay (LFA) is an attractive method for rapid, simple, and cost-effective point of care diagnosis. For LFA-based multiplex diagnosis of three viral intractable diseases (acquired immune deficiency syndrome and hepatitis C and A), here we developed proteinticle-based 7 different 3D probes that display different viral antigens on their surface, which were synthesized in Escherichia coli by self-assembly of human ferritin heavy chain that was already engineered by genetically linking viral antigens to its C-terminus. Each of the three test lines on LFA strip contains the proteinticle probes to detect disease-specific anti-viral antibodies. Compared to peptide probes, the proteinticle probes were evidently more sensitive, and the proteinticle probe-based LFA successfully diagnosed all the 20 patient sera per each disease without a false negative signal, whereas the diagnostic sensitivities in the peptide probe-based LFAs were 65-90%. Duplex and triplex assays performed with randomly mixed patient sera gave only true positive signals for all the 20 serum mixtures without any false positive signals, indicating 100% sensitivity and 100% specificity. It seems that on the proteinticle surface the antigenic peptides have homogeneous orientation and conformation without inter-peptide clustering and hence lead to the enhanced diagnostic performance with solving the problems of traditional diagnostic probes. Although the multiplex diagnosis of three viral diseases above was demonstrated as proof-of-concept here, the proposed LFA system can be applied to multiplex point of care diagnosis of other intractable diseases.

AB - Lateral flow assay (LFA) is an attractive method for rapid, simple, and cost-effective point of care diagnosis. For LFA-based multiplex diagnosis of three viral intractable diseases (acquired immune deficiency syndrome and hepatitis C and A), here we developed proteinticle-based 7 different 3D probes that display different viral antigens on their surface, which were synthesized in Escherichia coli by self-assembly of human ferritin heavy chain that was already engineered by genetically linking viral antigens to its C-terminus. Each of the three test lines on LFA strip contains the proteinticle probes to detect disease-specific anti-viral antibodies. Compared to peptide probes, the proteinticle probes were evidently more sensitive, and the proteinticle probe-based LFA successfully diagnosed all the 20 patient sera per each disease without a false negative signal, whereas the diagnostic sensitivities in the peptide probe-based LFAs were 65-90%. Duplex and triplex assays performed with randomly mixed patient sera gave only true positive signals for all the 20 serum mixtures without any false positive signals, indicating 100% sensitivity and 100% specificity. It seems that on the proteinticle surface the antigenic peptides have homogeneous orientation and conformation without inter-peptide clustering and hence lead to the enhanced diagnostic performance with solving the problems of traditional diagnostic probes. Although the multiplex diagnosis of three viral diseases above was demonstrated as proof-of-concept here, the proposed LFA system can be applied to multiplex point of care diagnosis of other intractable diseases.

KW - Infectious diseases

KW - Lateral flow assay

KW - Multiplex diagnosis

KW - Proteinticles

KW - Surface engineering

UR - http://www.scopus.com/inward/record.url?scp=84924192951&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84924192951&partnerID=8YFLogxK

U2 - 10.1016/j.bios.2015.02.033

DO - 10.1016/j.bios.2015.02.033

M3 - Article

VL - 69

SP - 213

EP - 225

JO - Biosensors

JF - Biosensors

SN - 0956-5663

ER -