Droplet Microfluidics Platform for Highly Sensitive and Quantitative Detection of Malaria-Causing Plasmodium Parasites Based on Enzyme Activity Measurement

Sissel  Juul; Christine Juul Fælled Nielsen; Rodrigo Labouriau; Amit Roy; Cinzia Tesauro; Pia Wrensted Jensen; Charlotte Harmsen; Emil Laust Kristoffersen; Ya-Ling Chiu; Rikke Frøhlich Hougaard; Paola Fiorani; Janet Cox-Singh; David Paul Tordrup; Jørn Erland Koch; Anne-Losi Bienvenu; Alessandro Desideri; Stephane Picot; Eskild Petersen; Kam W Leong; Yi-Ping Ho; Magnus Stougaard; Birgitta R Knudsen

doi:10.1021/nn3038594

Droplet Microfluidics Platform for Highly Sensitive and Quantitative Detection of Malaria-Causing Plasmodium Parasites Based on Enzyme Activity Measurement

Sissel Juul, Christine Juul Fælled Nielsen, Rodrigo Labouriau, Amit Roy, Cinzia Tesauro, Pia Wrensted Jensen, Charlotte Harmsen, Emil Laust Kristoffersen, Ya-Ling Chiu, Rikke Frøhlich Hougaard, Paola Fiorani, Janet Cox-Singh, David Paul Tordrup, Jørn Erland Koch, Anne-Losi Bienvenu, Alessandro Desideri, Stephane Picot, Eskild Petersen, Kam W Leong, Yi-Ping HoMagnus Stougaard, Birgitta R Knudsen

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

85 Citations (Scopus)

Abstract

We present an attractive new system for the specific and sensitive detection of the malaria-causing Plasmodium parasites. The system relies on isothermal conversion of single DNA cleavage–ligation events catalyzed specifically by the Plasmodium enzyme topoisomerase I to micrometer-sized products detectable at the single-molecule level. Combined with a droplet microfluidics lab-on-a-chip platform, this design allowed for sensitive, specific, and quantitative detection of all human-malaria-causing Plasmodium species in single drops of unprocessed blood with a detection limit of less than one parasite/μL. Moreover, the setup allowed for detection of Plasmodium parasites in noninvasive saliva samples from infected patients. During recent years malaria transmission has declined worldwide, and with this the number of patients with low-parasite density has increased. Consequently, the need for accurate detection of even a few parasites is becoming increasingly important for the continued combat against the disease. We believe that the presented droplet microfluidics platform, which has a high potential for adaptation to point-of-care setups suitable for low-resource settings, may contribute significantly to meet this demand. Moreover, potential future adaptation of the presented setup for the detection of other microorganisms may form the basis for the development of a more generic platform for diagnosis, fresh water or food quality control, or other purposes within applied or basic science.

Original language	English
Journal	A C S Nano
Volume	6
Issue	12
Pages (from-to)	10676-10683
Number of pages	8
ISSN	1936-0851
DOIs	https://doi.org/10.1021/nn3038594
Publication status	Published - Dec 2012

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Juul, S., Nielsen, C. J. F., Labouriau, R., Roy, A., Tesauro, C., Jensen, P. W., Harmsen, C., Kristoffersen, E. L., Chiu, Y.-L., Hougaard, R. F., Fiorani, P., Cox-Singh, J., Tordrup, D. P., Koch, J. E., Bienvenu, A.-L., Desideri, A., Picot, S., Petersen, E., Leong, K. W., ... Knudsen, B. R. (2012). Droplet Microfluidics Platform for Highly Sensitive and Quantitative Detection of Malaria-Causing Plasmodium Parasites Based on Enzyme Activity Measurement. A C S Nano, 6(12), 10676-10683. https://doi.org/10.1021/nn3038594

@article{e3ade0c099a34c0593a0d29c16b4f5e8,

title = "Droplet Microfluidics Platform for Highly Sensitive and Quantitative Detection of Malaria-Causing Plasmodium Parasites Based on Enzyme Activity Measurement",

abstract = "We present an attractive new system for the specific and sensitive detection of the malaria-causing Plasmodium parasites. The system relies on isothermal conversion of single DNA cleavage–ligation events catalyzed specifically by the Plasmodium enzyme topoisomerase I to micrometer-sized products detectable at the single-molecule level. Combined with a droplet microfluidics lab-on-a-chip platform, this design allowed for sensitive, specific, and quantitative detection of all human-malaria-causing Plasmodium species in single drops of unprocessed blood with a detection limit of less than one parasite/μL. Moreover, the setup allowed for detection of Plasmodium parasites in noninvasive saliva samples from infected patients. During recent years malaria transmission has declined worldwide, and with this the number of patients with low-parasite density has increased. Consequently, the need for accurate detection of even a few parasites is becoming increasingly important for the continued combat against the disease. We believe that the presented droplet microfluidics platform, which has a high potential for adaptation to point-of-care setups suitable for low-resource settings, may contribute significantly to meet this demand. Moreover, potential future adaptation of the presented setup for the detection of other microorganisms may form the basis for the development of a more generic platform for diagnosis, fresh water or food quality control, or other purposes within applied or basic science.",

author = "Sissel Juul and Nielsen, {Christine Juul F{\ae}lled} and Rodrigo Labouriau and Amit Roy and Cinzia Tesauro and Jensen, {Pia Wrensted} and Charlotte Harmsen and Kristoffersen, {Emil Laust} and Ya-Ling Chiu and Hougaard, {Rikke Fr{\o}hlich} and Paola Fiorani and Janet Cox-Singh and Tordrup, {David Paul} and Koch, {J{\o}rn Erland} and Anne-Losi Bienvenu and Alessandro Desideri and Stephane Picot and Eskild Petersen and Leong, {Kam W} and Yi-Ping Ho and Magnus Stougaard and Knudsen, {Birgitta R}",

year = "2012",

month = dec,

doi = "10.1021/nn3038594",

language = "English",

volume = "6",

pages = "10676--10683",

journal = "A C S Nano",

issn = "1936-0851",

publisher = "American Chemical Society",

number = "12",

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Juul, S, Nielsen, CJF, Labouriau, R, Roy, A, Tesauro, C, Jensen, PW, Harmsen, C, Kristoffersen, EL, Chiu, Y-L, Hougaard, RF, Fiorani, P, Cox-Singh, J, Tordrup, DP, Koch, JE, Bienvenu, A-L, Desideri, A, Picot, S, Petersen, E, Leong, KW, Ho, Y-P, Stougaard, M & Knudsen, BR 2012, 'Droplet Microfluidics Platform for Highly Sensitive and Quantitative Detection of Malaria-Causing Plasmodium Parasites Based on Enzyme Activity Measurement', A C S Nano, vol. 6, no. 12, pp. 10676-10683. https://doi.org/10.1021/nn3038594

Droplet Microfluidics Platform for Highly Sensitive and Quantitative Detection of Malaria-Causing Plasmodium Parasites Based on Enzyme Activity Measurement. / Juul, Sissel ; Nielsen, Christine Juul Fælled; Labouriau, Rodrigo et al.
In: A C S Nano, Vol. 6, No. 12, 12.2012, p. 10676-10683.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Droplet Microfluidics Platform for Highly Sensitive and Quantitative Detection of Malaria-Causing Plasmodium Parasites Based on Enzyme Activity Measurement

AU - Juul, Sissel

AU - Nielsen, Christine Juul Fælled

AU - Labouriau, Rodrigo

AU - Roy, Amit

AU - Tesauro, Cinzia

AU - Jensen, Pia Wrensted

AU - Harmsen, Charlotte

AU - Kristoffersen, Emil Laust

AU - Chiu, Ya-Ling

AU - Hougaard, Rikke Frøhlich

AU - Fiorani, Paola

AU - Cox-Singh, Janet

AU - Tordrup, David Paul

AU - Koch, Jørn Erland

AU - Bienvenu, Anne-Losi

AU - Desideri, Alessandro

AU - Picot, Stephane

AU - Petersen, Eskild

AU - Leong, Kam W

AU - Ho, Yi-Ping

AU - Stougaard, Magnus

AU - Knudsen, Birgitta R

PY - 2012/12

Y1 - 2012/12

N2 - We present an attractive new system for the specific and sensitive detection of the malaria-causing Plasmodium parasites. The system relies on isothermal conversion of single DNA cleavage–ligation events catalyzed specifically by the Plasmodium enzyme topoisomerase I to micrometer-sized products detectable at the single-molecule level. Combined with a droplet microfluidics lab-on-a-chip platform, this design allowed for sensitive, specific, and quantitative detection of all human-malaria-causing Plasmodium species in single drops of unprocessed blood with a detection limit of less than one parasite/μL. Moreover, the setup allowed for detection of Plasmodium parasites in noninvasive saliva samples from infected patients. During recent years malaria transmission has declined worldwide, and with this the number of patients with low-parasite density has increased. Consequently, the need for accurate detection of even a few parasites is becoming increasingly important for the continued combat against the disease. We believe that the presented droplet microfluidics platform, which has a high potential for adaptation to point-of-care setups suitable for low-resource settings, may contribute significantly to meet this demand. Moreover, potential future adaptation of the presented setup for the detection of other microorganisms may form the basis for the development of a more generic platform for diagnosis, fresh water or food quality control, or other purposes within applied or basic science.

AB - We present an attractive new system for the specific and sensitive detection of the malaria-causing Plasmodium parasites. The system relies on isothermal conversion of single DNA cleavage–ligation events catalyzed specifically by the Plasmodium enzyme topoisomerase I to micrometer-sized products detectable at the single-molecule level. Combined with a droplet microfluidics lab-on-a-chip platform, this design allowed for sensitive, specific, and quantitative detection of all human-malaria-causing Plasmodium species in single drops of unprocessed blood with a detection limit of less than one parasite/μL. Moreover, the setup allowed for detection of Plasmodium parasites in noninvasive saliva samples from infected patients. During recent years malaria transmission has declined worldwide, and with this the number of patients with low-parasite density has increased. Consequently, the need for accurate detection of even a few parasites is becoming increasingly important for the continued combat against the disease. We believe that the presented droplet microfluidics platform, which has a high potential for adaptation to point-of-care setups suitable for low-resource settings, may contribute significantly to meet this demand. Moreover, potential future adaptation of the presented setup for the detection of other microorganisms may form the basis for the development of a more generic platform for diagnosis, fresh water or food quality control, or other purposes within applied or basic science.

U2 - 10.1021/nn3038594

DO - 10.1021/nn3038594

M3 - Journal article

C2 - 23121492

SN - 1936-0851

VL - 6

SP - 10676

EP - 10683

JO - A C S Nano

JF - A C S Nano

IS - 12

ER -

Droplet Microfluidics Platform for Highly Sensitive and Quantitative Detection of Malaria-Causing Plasmodium Parasites Based on Enzyme Activity Measurement

Abstract

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