Abstract

A photonic integrated microfluidic device is demonstrated to perform optical excitation and forward scatter collection all on-chip in a planar format. Integrated on-chip optics formed a tailored beam geometry for optimal excitation of particles while a special design modification allowed for on-chip forward collection with the beam shaping capabilities. A notch was placed in the lens system that caused a dark spot on the facet of a collection waveguide while not affecting the beam geometry at the point of interrogation. The modified device with the ability to form a 10 μm beam geometry was demonstrated to detect the forward scatter from blank 5 μm diameter polystyrene beads. Free-space collection of side scatter signals was performed simultaneously with the on-chip collection and the designs demonstrated and enhanced SNR while the reliability of detection was determined to be appropriate for many applications. Excellent performance was confirmed via a false positive rate of 0.4%, a missed events rate of 6.8%, and a coincident rate of 96.3% as determined between simultaneously performed free-space and on-chip detection schemes.

© 2013 OSA

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2012 (6)

P. Fei, Z. Chen, Y. Men, A. Li, Y. Shen, and Y. Huang, “A compact optofluidic cytometer with integrated liquid-core/PDMS-cladding waveguides,” Lab Chip12(19), 3700–3706 (2012).
[CrossRef] [PubMed]

D. S. Boyle, K. R. Hawkins, M. S. Steele, M. Singhal, and X. Cheng, “Emerging technologies for point-of-care CD4 T-lymphocyte counting,” Trends Biotechnol.30(1), 45–54 (2012).
[CrossRef] [PubMed]

B. R. Watts, Z. Zhang, C.-Q. Xu, X. Cao, and M. Lin, “Integration of optical components on-chip for scattering and fluorescence detection in an optofluidic device,” Biomed. Opt. Express3(11), 2784–2793 (2012).
[CrossRef] [PubMed]

B. R. Watts, Z. Zhang, C.-Q. Xu, X. Cao, and M. Lin, “A photonic-microfluidic integrated device for reliable fluorescence detection and counting,” Electrophoresis33(21), 3236–3244 (2012).
[CrossRef] [PubMed]

B. R. Watts, T. Kowpak, Z. Zhang, C.-Q. Xu, S. Zhu, X. Cao, and M. Lin, “Fabrication and performance of a photonic-microfluidic integrated device,” Micromachines3(4), 62–77 (2012).
[CrossRef]

X. Mao, A. A. Nawaz, S.-C. S. Lin, M. I. Lapsley, Y. Zhao, J. P. McCoy, W. S. El-Deiry, and T. J. Huang, “An integrated, multiparametric flow cytometry chip using ‘microfluidic drifting’ based three-dimensional hydrodynamic focusing,” Biomicrofluidics6(2), 024113 (2012).
[CrossRef] [PubMed]

2011 (4)

Z. Zhang, P. Zhao, G. Xiao, B. R. Watts, and C.-Q. Xu, “Sealing SU-8 microfluidic channels using PDMS,” Biomicrofluidics5(4), 046503 (2011).
[CrossRef] [PubMed]

M. Frankowski, N. Bock, A. Kummrow, S. Schädel-Ebner, M. Schmidt, A. Tuchscheerer, and J. Neukammer, “A microflow cytometer exploited for the immunological differentiation of leukocytes,” Cytometry A79A(8), 613–624 (2011).
[CrossRef] [PubMed]

M. Rosenauer, W. Buchegger, I. Finoulst, P. Verhaert, and M. Vellekoop, “Miniaturized flow cytometer with 3D hydrodynamic particle focusing and integrated optical elements applying silicon photodiodes,” Microfluid. Nanofluid.10(4), 761–771 (2011).
[CrossRef]

N. Hashemi, J. S. Erickson, J. P. Golden, K. M. Jackson, and F. S. Ligler, “Microflow cytometer for optical analysis of phytoplankton,” Biosens. Bioelectron.26(11), 4263–4269 (2011).
[CrossRef] [PubMed]

2010 (7)

D. Heikali and D. Di Carlo, “A niche for microfluidics in portable hematology analyzers,” J. Assoc. Lab. Autom.15(4), 319–328 (2010).
[CrossRef]

M. Rosenauer and M. J. Vellekoop, “Characterization of a microflow cytometer with an integrated three-dimensional optofluidic lens system,” Biomicrofluidics4(4), 043005 (2010).
[CrossRef] [PubMed]

S. H. Cho, J. M. Godin, C.-H. Chen, W. Qiao, H. Lee, and Y.-H. Lo, “Review article: recent advancements in optofluidic flow cytometer,” Biomicrofluidics4(4), 043001 (2010).
[CrossRef] [PubMed]

W. G. Lee, Y.-G. Kim, B. G. Chung, U. Demirci, and A. Khademhosseini, “Nano/microfluidics for diagnosis of infectious diseases in developing countries,” Adv. Drug Deliv. Rev.62(4-5), 449–457 (2010).
[CrossRef] [PubMed]

J. Godin and Y.-H. Lo, “Two-parameter angular light scatter collection for microfluidic flow cytometry by unique waveguide structures,” Biomed. Opt. Express1(5), 1472–1479 (2010).
[CrossRef] [PubMed]

B. R. Watts, T. Kowpak, Z. Zhang, C. Q. Xu, and S. Zhu, “Formation and characterization of an ideal excitation beam geometry in an optofluidic device,” Biomed. Opt. Express1(3), 848–860 (2010).
[CrossRef] [PubMed]

T. Kowpak, B. R. Watts, Z. Zhang, S. Zhu, and C.-Q. Xu, “Fabrication of photonic/microfluidic integrated devices using an epoxy photoresist,” Macromol. Mater. Eng.295(6), 559–565 (2010).
[CrossRef]

2009 (2)

P. L. Bergquist, E. M. Hardiman, B. C. Ferrari, and T. Winsley, “Applications of flow cytometry in environmental microbiology and biotechnology,” Extremophiles13(3), 389–401 (2009).
[CrossRef] [PubMed]

M. Ikeda, N. Yamaguchi, and M. Nasu, “Rapid on-chip flow cytometric detection of Listeria monocytogenes in milk,” J. Health Sci.55(5), 851–856 (2009).
[CrossRef]

2008 (1)

D. A. Ateya, J. S. Erickson, P. B. Howell, L. R. Hilliard, J. P. Golden, and F. S. Ligler, “The good, the bad, and the tiny: a review of microflow cytometry,” Anal. Bioanal. Chem.391(5), 1485–1498 (2008).
[CrossRef] [PubMed]

2007 (1)

T. D. Chung and H. C. Kim, “Recent advances in miniaturized microfluidic flow cytometry for clinical use,” Electrophoresis28(24), 4511–4520 (2007).
[CrossRef] [PubMed]

2005 (2)

B. H. Robertson and J. K. A. Nicholson, “New microbiology tools for public health and their implications,” Annu. Rev. Public Health26(1), 281–302 (2005).
[CrossRef] [PubMed]

D. Huh, W. Gu, Y. Kamotani, J. B. Grotberg, and S. Takayama, “Microfluidics for flow cytometric analysis of cells and particles,” Physiol. Meas.26(3), R73–R98 (2005).
[CrossRef] [PubMed]

2003 (1)

1998 (1)

Y. Xia and G. M. Whitesides, “Soft lithography,” Annu. Rev. Mater. Sci.28(1), 153–184 (1998).
[CrossRef]

Ateya, D. A.

D. A. Ateya, J. S. Erickson, P. B. Howell, L. R. Hilliard, J. P. Golden, and F. S. Ligler, “The good, the bad, and the tiny: a review of microflow cytometry,” Anal. Bioanal. Chem.391(5), 1485–1498 (2008).
[CrossRef] [PubMed]

Bergquist, P. L.

P. L. Bergquist, E. M. Hardiman, B. C. Ferrari, and T. Winsley, “Applications of flow cytometry in environmental microbiology and biotechnology,” Extremophiles13(3), 389–401 (2009).
[CrossRef] [PubMed]

Bock, N.

M. Frankowski, N. Bock, A. Kummrow, S. Schädel-Ebner, M. Schmidt, A. Tuchscheerer, and J. Neukammer, “A microflow cytometer exploited for the immunological differentiation of leukocytes,” Cytometry A79A(8), 613–624 (2011).
[CrossRef] [PubMed]

Boyle, D. S.

D. S. Boyle, K. R. Hawkins, M. S. Steele, M. Singhal, and X. Cheng, “Emerging technologies for point-of-care CD4 T-lymphocyte counting,” Trends Biotechnol.30(1), 45–54 (2012).
[CrossRef] [PubMed]

Buchegger, W.

M. Rosenauer, W. Buchegger, I. Finoulst, P. Verhaert, and M. Vellekoop, “Miniaturized flow cytometer with 3D hydrodynamic particle focusing and integrated optical elements applying silicon photodiodes,” Microfluid. Nanofluid.10(4), 761–771 (2011).
[CrossRef]

Cao, X.

B. R. Watts, Z. Zhang, C.-Q. Xu, X. Cao, and M. Lin, “A photonic-microfluidic integrated device for reliable fluorescence detection and counting,” Electrophoresis33(21), 3236–3244 (2012).
[CrossRef] [PubMed]

B. R. Watts, T. Kowpak, Z. Zhang, C.-Q. Xu, S. Zhu, X. Cao, and M. Lin, “Fabrication and performance of a photonic-microfluidic integrated device,” Micromachines3(4), 62–77 (2012).
[CrossRef]

B. R. Watts, Z. Zhang, C.-Q. Xu, X. Cao, and M. Lin, “Integration of optical components on-chip for scattering and fluorescence detection in an optofluidic device,” Biomed. Opt. Express3(11), 2784–2793 (2012).
[CrossRef] [PubMed]

C. Mu, Z. Zhang, M. Lin, X. Cao, B. R. Watts, and C.-Q. Xu, “Strong fluidic interconnections for optofluidic devices” (submitted toSens. Actuators B).

Chen, C.-H.

S. H. Cho, J. M. Godin, C.-H. Chen, W. Qiao, H. Lee, and Y.-H. Lo, “Review article: recent advancements in optofluidic flow cytometer,” Biomicrofluidics4(4), 043001 (2010).
[CrossRef] [PubMed]

Chen, Z.

P. Fei, Z. Chen, Y. Men, A. Li, Y. Shen, and Y. Huang, “A compact optofluidic cytometer with integrated liquid-core/PDMS-cladding waveguides,” Lab Chip12(19), 3700–3706 (2012).
[CrossRef] [PubMed]

Cheng, X.

D. S. Boyle, K. R. Hawkins, M. S. Steele, M. Singhal, and X. Cheng, “Emerging technologies for point-of-care CD4 T-lymphocyte counting,” Trends Biotechnol.30(1), 45–54 (2012).
[CrossRef] [PubMed]

Cho, S. H.

S. H. Cho, J. M. Godin, C.-H. Chen, W. Qiao, H. Lee, and Y.-H. Lo, “Review article: recent advancements in optofluidic flow cytometer,” Biomicrofluidics4(4), 043001 (2010).
[CrossRef] [PubMed]

Chung, B. G.

W. G. Lee, Y.-G. Kim, B. G. Chung, U. Demirci, and A. Khademhosseini, “Nano/microfluidics for diagnosis of infectious diseases in developing countries,” Adv. Drug Deliv. Rev.62(4-5), 449–457 (2010).
[CrossRef] [PubMed]

Chung, T. D.

T. D. Chung and H. C. Kim, “Recent advances in miniaturized microfluidic flow cytometry for clinical use,” Electrophoresis28(24), 4511–4520 (2007).
[CrossRef] [PubMed]

Demirci, U.

W. G. Lee, Y.-G. Kim, B. G. Chung, U. Demirci, and A. Khademhosseini, “Nano/microfluidics for diagnosis of infectious diseases in developing countries,” Adv. Drug Deliv. Rev.62(4-5), 449–457 (2010).
[CrossRef] [PubMed]

Di Carlo, D.

D. Heikali and D. Di Carlo, “A niche for microfluidics in portable hematology analyzers,” J. Assoc. Lab. Autom.15(4), 319–328 (2010).
[CrossRef]

El-Ali, J.

El-Deiry, W. S.

X. Mao, A. A. Nawaz, S.-C. S. Lin, M. I. Lapsley, Y. Zhao, J. P. McCoy, W. S. El-Deiry, and T. J. Huang, “An integrated, multiparametric flow cytometry chip using ‘microfluidic drifting’ based three-dimensional hydrodynamic focusing,” Biomicrofluidics6(2), 024113 (2012).
[CrossRef] [PubMed]

Erickson, J. S.

N. Hashemi, J. S. Erickson, J. P. Golden, K. M. Jackson, and F. S. Ligler, “Microflow cytometer for optical analysis of phytoplankton,” Biosens. Bioelectron.26(11), 4263–4269 (2011).
[CrossRef] [PubMed]

D. A. Ateya, J. S. Erickson, P. B. Howell, L. R. Hilliard, J. P. Golden, and F. S. Ligler, “The good, the bad, and the tiny: a review of microflow cytometry,” Anal. Bioanal. Chem.391(5), 1485–1498 (2008).
[CrossRef] [PubMed]

Fei, P.

P. Fei, Z. Chen, Y. Men, A. Li, Y. Shen, and Y. Huang, “A compact optofluidic cytometer with integrated liquid-core/PDMS-cladding waveguides,” Lab Chip12(19), 3700–3706 (2012).
[CrossRef] [PubMed]

Ferrari, B. C.

P. L. Bergquist, E. M. Hardiman, B. C. Ferrari, and T. Winsley, “Applications of flow cytometry in environmental microbiology and biotechnology,” Extremophiles13(3), 389–401 (2009).
[CrossRef] [PubMed]

Finoulst, I.

M. Rosenauer, W. Buchegger, I. Finoulst, P. Verhaert, and M. Vellekoop, “Miniaturized flow cytometer with 3D hydrodynamic particle focusing and integrated optical elements applying silicon photodiodes,” Microfluid. Nanofluid.10(4), 761–771 (2011).
[CrossRef]

Frankowski, M.

M. Frankowski, N. Bock, A. Kummrow, S. Schädel-Ebner, M. Schmidt, A. Tuchscheerer, and J. Neukammer, “A microflow cytometer exploited for the immunological differentiation of leukocytes,” Cytometry A79A(8), 613–624 (2011).
[CrossRef] [PubMed]

Godin, J.

Godin, J. M.

S. H. Cho, J. M. Godin, C.-H. Chen, W. Qiao, H. Lee, and Y.-H. Lo, “Review article: recent advancements in optofluidic flow cytometer,” Biomicrofluidics4(4), 043001 (2010).
[CrossRef] [PubMed]

Golden, J. P.

N. Hashemi, J. S. Erickson, J. P. Golden, K. M. Jackson, and F. S. Ligler, “Microflow cytometer for optical analysis of phytoplankton,” Biosens. Bioelectron.26(11), 4263–4269 (2011).
[CrossRef] [PubMed]

D. A. Ateya, J. S. Erickson, P. B. Howell, L. R. Hilliard, J. P. Golden, and F. S. Ligler, “The good, the bad, and the tiny: a review of microflow cytometry,” Anal. Bioanal. Chem.391(5), 1485–1498 (2008).
[CrossRef] [PubMed]

Grotberg, J. B.

D. Huh, W. Gu, Y. Kamotani, J. B. Grotberg, and S. Takayama, “Microfluidics for flow cytometric analysis of cells and particles,” Physiol. Meas.26(3), R73–R98 (2005).
[CrossRef] [PubMed]

Gu, W.

D. Huh, W. Gu, Y. Kamotani, J. B. Grotberg, and S. Takayama, “Microfluidics for flow cytometric analysis of cells and particles,” Physiol. Meas.26(3), R73–R98 (2005).
[CrossRef] [PubMed]

Hardiman, E. M.

P. L. Bergquist, E. M. Hardiman, B. C. Ferrari, and T. Winsley, “Applications of flow cytometry in environmental microbiology and biotechnology,” Extremophiles13(3), 389–401 (2009).
[CrossRef] [PubMed]

Hashemi, N.

N. Hashemi, J. S. Erickson, J. P. Golden, K. M. Jackson, and F. S. Ligler, “Microflow cytometer for optical analysis of phytoplankton,” Biosens. Bioelectron.26(11), 4263–4269 (2011).
[CrossRef] [PubMed]

Hawkins, K. R.

D. S. Boyle, K. R. Hawkins, M. S. Steele, M. Singhal, and X. Cheng, “Emerging technologies for point-of-care CD4 T-lymphocyte counting,” Trends Biotechnol.30(1), 45–54 (2012).
[CrossRef] [PubMed]

Heikali, D.

D. Heikali and D. Di Carlo, “A niche for microfluidics in portable hematology analyzers,” J. Assoc. Lab. Autom.15(4), 319–328 (2010).
[CrossRef]

Hilliard, L. R.

D. A. Ateya, J. S. Erickson, P. B. Howell, L. R. Hilliard, J. P. Golden, and F. S. Ligler, “The good, the bad, and the tiny: a review of microflow cytometry,” Anal. Bioanal. Chem.391(5), 1485–1498 (2008).
[CrossRef] [PubMed]

Howell, P. B.

D. A. Ateya, J. S. Erickson, P. B. Howell, L. R. Hilliard, J. P. Golden, and F. S. Ligler, “The good, the bad, and the tiny: a review of microflow cytometry,” Anal. Bioanal. Chem.391(5), 1485–1498 (2008).
[CrossRef] [PubMed]

Huang, T. J.

X. Mao, A. A. Nawaz, S.-C. S. Lin, M. I. Lapsley, Y. Zhao, J. P. McCoy, W. S. El-Deiry, and T. J. Huang, “An integrated, multiparametric flow cytometry chip using ‘microfluidic drifting’ based three-dimensional hydrodynamic focusing,” Biomicrofluidics6(2), 024113 (2012).
[CrossRef] [PubMed]

Huang, Y.

P. Fei, Z. Chen, Y. Men, A. Li, Y. Shen, and Y. Huang, “A compact optofluidic cytometer with integrated liquid-core/PDMS-cladding waveguides,” Lab Chip12(19), 3700–3706 (2012).
[CrossRef] [PubMed]

Huh, D.

D. Huh, W. Gu, Y. Kamotani, J. B. Grotberg, and S. Takayama, “Microfluidics for flow cytometric analysis of cells and particles,” Physiol. Meas.26(3), R73–R98 (2005).
[CrossRef] [PubMed]

Ikeda, M.

M. Ikeda, N. Yamaguchi, and M. Nasu, “Rapid on-chip flow cytometric detection of Listeria monocytogenes in milk,” J. Health Sci.55(5), 851–856 (2009).
[CrossRef]

Jackson, K. M.

N. Hashemi, J. S. Erickson, J. P. Golden, K. M. Jackson, and F. S. Ligler, “Microflow cytometer for optical analysis of phytoplankton,” Biosens. Bioelectron.26(11), 4263–4269 (2011).
[CrossRef] [PubMed]

Kamotani, Y.

D. Huh, W. Gu, Y. Kamotani, J. B. Grotberg, and S. Takayama, “Microfluidics for flow cytometric analysis of cells and particles,” Physiol. Meas.26(3), R73–R98 (2005).
[CrossRef] [PubMed]

Khademhosseini, A.

W. G. Lee, Y.-G. Kim, B. G. Chung, U. Demirci, and A. Khademhosseini, “Nano/microfluidics for diagnosis of infectious diseases in developing countries,” Adv. Drug Deliv. Rev.62(4-5), 449–457 (2010).
[CrossRef] [PubMed]

Kim, H. C.

T. D. Chung and H. C. Kim, “Recent advances in miniaturized microfluidic flow cytometry for clinical use,” Electrophoresis28(24), 4511–4520 (2007).
[CrossRef] [PubMed]

Kim, Y.-G.

W. G. Lee, Y.-G. Kim, B. G. Chung, U. Demirci, and A. Khademhosseini, “Nano/microfluidics for diagnosis of infectious diseases in developing countries,” Adv. Drug Deliv. Rev.62(4-5), 449–457 (2010).
[CrossRef] [PubMed]

Kowpak, T.

B. R. Watts, T. Kowpak, Z. Zhang, C.-Q. Xu, S. Zhu, X. Cao, and M. Lin, “Fabrication and performance of a photonic-microfluidic integrated device,” Micromachines3(4), 62–77 (2012).
[CrossRef]

T. Kowpak, B. R. Watts, Z. Zhang, S. Zhu, and C.-Q. Xu, “Fabrication of photonic/microfluidic integrated devices using an epoxy photoresist,” Macromol. Mater. Eng.295(6), 559–565 (2010).
[CrossRef]

B. R. Watts, T. Kowpak, Z. Zhang, C. Q. Xu, and S. Zhu, “Formation and characterization of an ideal excitation beam geometry in an optofluidic device,” Biomed. Opt. Express1(3), 848–860 (2010).
[CrossRef] [PubMed]

Kummrow, A.

M. Frankowski, N. Bock, A. Kummrow, S. Schädel-Ebner, M. Schmidt, A. Tuchscheerer, and J. Neukammer, “A microflow cytometer exploited for the immunological differentiation of leukocytes,” Cytometry A79A(8), 613–624 (2011).
[CrossRef] [PubMed]

Kutter, J. P.

Lapsley, M. I.

X. Mao, A. A. Nawaz, S.-C. S. Lin, M. I. Lapsley, Y. Zhao, J. P. McCoy, W. S. El-Deiry, and T. J. Huang, “An integrated, multiparametric flow cytometry chip using ‘microfluidic drifting’ based three-dimensional hydrodynamic focusing,” Biomicrofluidics6(2), 024113 (2012).
[CrossRef] [PubMed]

Lee, H.

S. H. Cho, J. M. Godin, C.-H. Chen, W. Qiao, H. Lee, and Y.-H. Lo, “Review article: recent advancements in optofluidic flow cytometer,” Biomicrofluidics4(4), 043001 (2010).
[CrossRef] [PubMed]

Lee, W. G.

W. G. Lee, Y.-G. Kim, B. G. Chung, U. Demirci, and A. Khademhosseini, “Nano/microfluidics for diagnosis of infectious diseases in developing countries,” Adv. Drug Deliv. Rev.62(4-5), 449–457 (2010).
[CrossRef] [PubMed]

Li, A.

P. Fei, Z. Chen, Y. Men, A. Li, Y. Shen, and Y. Huang, “A compact optofluidic cytometer with integrated liquid-core/PDMS-cladding waveguides,” Lab Chip12(19), 3700–3706 (2012).
[CrossRef] [PubMed]

Ligler, F. S.

N. Hashemi, J. S. Erickson, J. P. Golden, K. M. Jackson, and F. S. Ligler, “Microflow cytometer for optical analysis of phytoplankton,” Biosens. Bioelectron.26(11), 4263–4269 (2011).
[CrossRef] [PubMed]

D. A. Ateya, J. S. Erickson, P. B. Howell, L. R. Hilliard, J. P. Golden, and F. S. Ligler, “The good, the bad, and the tiny: a review of microflow cytometry,” Anal. Bioanal. Chem.391(5), 1485–1498 (2008).
[CrossRef] [PubMed]

Lin, M.

B. R. Watts, Z. Zhang, C.-Q. Xu, X. Cao, and M. Lin, “A photonic-microfluidic integrated device for reliable fluorescence detection and counting,” Electrophoresis33(21), 3236–3244 (2012).
[CrossRef] [PubMed]

B. R. Watts, T. Kowpak, Z. Zhang, C.-Q. Xu, S. Zhu, X. Cao, and M. Lin, “Fabrication and performance of a photonic-microfluidic integrated device,” Micromachines3(4), 62–77 (2012).
[CrossRef]

B. R. Watts, Z. Zhang, C.-Q. Xu, X. Cao, and M. Lin, “Integration of optical components on-chip for scattering and fluorescence detection in an optofluidic device,” Biomed. Opt. Express3(11), 2784–2793 (2012).
[CrossRef] [PubMed]

C. Mu, Z. Zhang, M. Lin, X. Cao, B. R. Watts, and C.-Q. Xu, “Strong fluidic interconnections for optofluidic devices” (submitted toSens. Actuators B).

Lin, S.-C. S.

X. Mao, A. A. Nawaz, S.-C. S. Lin, M. I. Lapsley, Y. Zhao, J. P. McCoy, W. S. El-Deiry, and T. J. Huang, “An integrated, multiparametric flow cytometry chip using ‘microfluidic drifting’ based three-dimensional hydrodynamic focusing,” Biomicrofluidics6(2), 024113 (2012).
[CrossRef] [PubMed]

Lo, Y.-H.

S. H. Cho, J. M. Godin, C.-H. Chen, W. Qiao, H. Lee, and Y.-H. Lo, “Review article: recent advancements in optofluidic flow cytometer,” Biomicrofluidics4(4), 043001 (2010).
[CrossRef] [PubMed]

J. Godin and Y.-H. Lo, “Two-parameter angular light scatter collection for microfluidic flow cytometry by unique waveguide structures,” Biomed. Opt. Express1(5), 1472–1479 (2010).
[CrossRef] [PubMed]

Mao, X.

X. Mao, A. A. Nawaz, S.-C. S. Lin, M. I. Lapsley, Y. Zhao, J. P. McCoy, W. S. El-Deiry, and T. J. Huang, “An integrated, multiparametric flow cytometry chip using ‘microfluidic drifting’ based three-dimensional hydrodynamic focusing,” Biomicrofluidics6(2), 024113 (2012).
[CrossRef] [PubMed]

McCoy, J. P.

X. Mao, A. A. Nawaz, S.-C. S. Lin, M. I. Lapsley, Y. Zhao, J. P. McCoy, W. S. El-Deiry, and T. J. Huang, “An integrated, multiparametric flow cytometry chip using ‘microfluidic drifting’ based three-dimensional hydrodynamic focusing,” Biomicrofluidics6(2), 024113 (2012).
[CrossRef] [PubMed]

Men, Y.

P. Fei, Z. Chen, Y. Men, A. Li, Y. Shen, and Y. Huang, “A compact optofluidic cytometer with integrated liquid-core/PDMS-cladding waveguides,” Lab Chip12(19), 3700–3706 (2012).
[CrossRef] [PubMed]

Mogensen, K. B.

Mu, C.

C. Mu, Z. Zhang, M. Lin, X. Cao, B. R. Watts, and C.-Q. Xu, “Strong fluidic interconnections for optofluidic devices” (submitted toSens. Actuators B).

Nasu, M.

M. Ikeda, N. Yamaguchi, and M. Nasu, “Rapid on-chip flow cytometric detection of Listeria monocytogenes in milk,” J. Health Sci.55(5), 851–856 (2009).
[CrossRef]

Nawaz, A. A.

X. Mao, A. A. Nawaz, S.-C. S. Lin, M. I. Lapsley, Y. Zhao, J. P. McCoy, W. S. El-Deiry, and T. J. Huang, “An integrated, multiparametric flow cytometry chip using ‘microfluidic drifting’ based three-dimensional hydrodynamic focusing,” Biomicrofluidics6(2), 024113 (2012).
[CrossRef] [PubMed]

Neukammer, J.

M. Frankowski, N. Bock, A. Kummrow, S. Schädel-Ebner, M. Schmidt, A. Tuchscheerer, and J. Neukammer, “A microflow cytometer exploited for the immunological differentiation of leukocytes,” Cytometry A79A(8), 613–624 (2011).
[CrossRef] [PubMed]

Nicholson, J. K. A.

B. H. Robertson and J. K. A. Nicholson, “New microbiology tools for public health and their implications,” Annu. Rev. Public Health26(1), 281–302 (2005).
[CrossRef] [PubMed]

Qiao, W.

S. H. Cho, J. M. Godin, C.-H. Chen, W. Qiao, H. Lee, and Y.-H. Lo, “Review article: recent advancements in optofluidic flow cytometer,” Biomicrofluidics4(4), 043001 (2010).
[CrossRef] [PubMed]

Robertson, B. H.

B. H. Robertson and J. K. A. Nicholson, “New microbiology tools for public health and their implications,” Annu. Rev. Public Health26(1), 281–302 (2005).
[CrossRef] [PubMed]

Rosenauer, M.

M. Rosenauer, W. Buchegger, I. Finoulst, P. Verhaert, and M. Vellekoop, “Miniaturized flow cytometer with 3D hydrodynamic particle focusing and integrated optical elements applying silicon photodiodes,” Microfluid. Nanofluid.10(4), 761–771 (2011).
[CrossRef]

M. Rosenauer and M. J. Vellekoop, “Characterization of a microflow cytometer with an integrated three-dimensional optofluidic lens system,” Biomicrofluidics4(4), 043005 (2010).
[CrossRef] [PubMed]

Schädel-Ebner, S.

M. Frankowski, N. Bock, A. Kummrow, S. Schädel-Ebner, M. Schmidt, A. Tuchscheerer, and J. Neukammer, “A microflow cytometer exploited for the immunological differentiation of leukocytes,” Cytometry A79A(8), 613–624 (2011).
[CrossRef] [PubMed]

Schmidt, M.

M. Frankowski, N. Bock, A. Kummrow, S. Schädel-Ebner, M. Schmidt, A. Tuchscheerer, and J. Neukammer, “A microflow cytometer exploited for the immunological differentiation of leukocytes,” Cytometry A79A(8), 613–624 (2011).
[CrossRef] [PubMed]

Shen, Y.

P. Fei, Z. Chen, Y. Men, A. Li, Y. Shen, and Y. Huang, “A compact optofluidic cytometer with integrated liquid-core/PDMS-cladding waveguides,” Lab Chip12(19), 3700–3706 (2012).
[CrossRef] [PubMed]

Singhal, M.

D. S. Boyle, K. R. Hawkins, M. S. Steele, M. Singhal, and X. Cheng, “Emerging technologies for point-of-care CD4 T-lymphocyte counting,” Trends Biotechnol.30(1), 45–54 (2012).
[CrossRef] [PubMed]

Steele, M. S.

D. S. Boyle, K. R. Hawkins, M. S. Steele, M. Singhal, and X. Cheng, “Emerging technologies for point-of-care CD4 T-lymphocyte counting,” Trends Biotechnol.30(1), 45–54 (2012).
[CrossRef] [PubMed]

Takayama, S.

D. Huh, W. Gu, Y. Kamotani, J. B. Grotberg, and S. Takayama, “Microfluidics for flow cytometric analysis of cells and particles,” Physiol. Meas.26(3), R73–R98 (2005).
[CrossRef] [PubMed]

Tuchscheerer, A.

M. Frankowski, N. Bock, A. Kummrow, S. Schädel-Ebner, M. Schmidt, A. Tuchscheerer, and J. Neukammer, “A microflow cytometer exploited for the immunological differentiation of leukocytes,” Cytometry A79A(8), 613–624 (2011).
[CrossRef] [PubMed]

Vellekoop, M.

M. Rosenauer, W. Buchegger, I. Finoulst, P. Verhaert, and M. Vellekoop, “Miniaturized flow cytometer with 3D hydrodynamic particle focusing and integrated optical elements applying silicon photodiodes,” Microfluid. Nanofluid.10(4), 761–771 (2011).
[CrossRef]

Vellekoop, M. J.

M. Rosenauer and M. J. Vellekoop, “Characterization of a microflow cytometer with an integrated three-dimensional optofluidic lens system,” Biomicrofluidics4(4), 043005 (2010).
[CrossRef] [PubMed]

Verhaert, P.

M. Rosenauer, W. Buchegger, I. Finoulst, P. Verhaert, and M. Vellekoop, “Miniaturized flow cytometer with 3D hydrodynamic particle focusing and integrated optical elements applying silicon photodiodes,” Microfluid. Nanofluid.10(4), 761–771 (2011).
[CrossRef]

Watts, B. R.

B. R. Watts, Z. Zhang, C.-Q. Xu, X. Cao, and M. Lin, “A photonic-microfluidic integrated device for reliable fluorescence detection and counting,” Electrophoresis33(21), 3236–3244 (2012).
[CrossRef] [PubMed]

B. R. Watts, T. Kowpak, Z. Zhang, C.-Q. Xu, S. Zhu, X. Cao, and M. Lin, “Fabrication and performance of a photonic-microfluidic integrated device,” Micromachines3(4), 62–77 (2012).
[CrossRef]

B. R. Watts, Z. Zhang, C.-Q. Xu, X. Cao, and M. Lin, “Integration of optical components on-chip for scattering and fluorescence detection in an optofluidic device,” Biomed. Opt. Express3(11), 2784–2793 (2012).
[CrossRef] [PubMed]

Z. Zhang, P. Zhao, G. Xiao, B. R. Watts, and C.-Q. Xu, “Sealing SU-8 microfluidic channels using PDMS,” Biomicrofluidics5(4), 046503 (2011).
[CrossRef] [PubMed]

T. Kowpak, B. R. Watts, Z. Zhang, S. Zhu, and C.-Q. Xu, “Fabrication of photonic/microfluidic integrated devices using an epoxy photoresist,” Macromol. Mater. Eng.295(6), 559–565 (2010).
[CrossRef]

B. R. Watts, T. Kowpak, Z. Zhang, C. Q. Xu, and S. Zhu, “Formation and characterization of an ideal excitation beam geometry in an optofluidic device,” Biomed. Opt. Express1(3), 848–860 (2010).
[CrossRef] [PubMed]

C. Mu, Z. Zhang, M. Lin, X. Cao, B. R. Watts, and C.-Q. Xu, “Strong fluidic interconnections for optofluidic devices” (submitted toSens. Actuators B).

Whitesides, G. M.

Y. Xia and G. M. Whitesides, “Soft lithography,” Annu. Rev. Mater. Sci.28(1), 153–184 (1998).
[CrossRef]

Winsley, T.

P. L. Bergquist, E. M. Hardiman, B. C. Ferrari, and T. Winsley, “Applications of flow cytometry in environmental microbiology and biotechnology,” Extremophiles13(3), 389–401 (2009).
[CrossRef] [PubMed]

Wolff, A.

Xia, Y.

Y. Xia and G. M. Whitesides, “Soft lithography,” Annu. Rev. Mater. Sci.28(1), 153–184 (1998).
[CrossRef]

Xiao, G.

Z. Zhang, P. Zhao, G. Xiao, B. R. Watts, and C.-Q. Xu, “Sealing SU-8 microfluidic channels using PDMS,” Biomicrofluidics5(4), 046503 (2011).
[CrossRef] [PubMed]

Xu, C. Q.

Xu, C.-Q.

B. R. Watts, Z. Zhang, C.-Q. Xu, X. Cao, and M. Lin, “Integration of optical components on-chip for scattering and fluorescence detection in an optofluidic device,” Biomed. Opt. Express3(11), 2784–2793 (2012).
[CrossRef] [PubMed]

B. R. Watts, T. Kowpak, Z. Zhang, C.-Q. Xu, S. Zhu, X. Cao, and M. Lin, “Fabrication and performance of a photonic-microfluidic integrated device,” Micromachines3(4), 62–77 (2012).
[CrossRef]

B. R. Watts, Z. Zhang, C.-Q. Xu, X. Cao, and M. Lin, “A photonic-microfluidic integrated device for reliable fluorescence detection and counting,” Electrophoresis33(21), 3236–3244 (2012).
[CrossRef] [PubMed]

Z. Zhang, P. Zhao, G. Xiao, B. R. Watts, and C.-Q. Xu, “Sealing SU-8 microfluidic channels using PDMS,” Biomicrofluidics5(4), 046503 (2011).
[CrossRef] [PubMed]

T. Kowpak, B. R. Watts, Z. Zhang, S. Zhu, and C.-Q. Xu, “Fabrication of photonic/microfluidic integrated devices using an epoxy photoresist,” Macromol. Mater. Eng.295(6), 559–565 (2010).
[CrossRef]

C. Mu, Z. Zhang, M. Lin, X. Cao, B. R. Watts, and C.-Q. Xu, “Strong fluidic interconnections for optofluidic devices” (submitted toSens. Actuators B).

Yamaguchi, N.

M. Ikeda, N. Yamaguchi, and M. Nasu, “Rapid on-chip flow cytometric detection of Listeria monocytogenes in milk,” J. Health Sci.55(5), 851–856 (2009).
[CrossRef]

Zhang, Z.

B. R. Watts, Z. Zhang, C.-Q. Xu, X. Cao, and M. Lin, “A photonic-microfluidic integrated device for reliable fluorescence detection and counting,” Electrophoresis33(21), 3236–3244 (2012).
[CrossRef] [PubMed]

B. R. Watts, T. Kowpak, Z. Zhang, C.-Q. Xu, S. Zhu, X. Cao, and M. Lin, “Fabrication and performance of a photonic-microfluidic integrated device,” Micromachines3(4), 62–77 (2012).
[CrossRef]

B. R. Watts, Z. Zhang, C.-Q. Xu, X. Cao, and M. Lin, “Integration of optical components on-chip for scattering and fluorescence detection in an optofluidic device,” Biomed. Opt. Express3(11), 2784–2793 (2012).
[CrossRef] [PubMed]

Z. Zhang, P. Zhao, G. Xiao, B. R. Watts, and C.-Q. Xu, “Sealing SU-8 microfluidic channels using PDMS,” Biomicrofluidics5(4), 046503 (2011).
[CrossRef] [PubMed]

T. Kowpak, B. R. Watts, Z. Zhang, S. Zhu, and C.-Q. Xu, “Fabrication of photonic/microfluidic integrated devices using an epoxy photoresist,” Macromol. Mater. Eng.295(6), 559–565 (2010).
[CrossRef]

B. R. Watts, T. Kowpak, Z. Zhang, C. Q. Xu, and S. Zhu, “Formation and characterization of an ideal excitation beam geometry in an optofluidic device,” Biomed. Opt. Express1(3), 848–860 (2010).
[CrossRef] [PubMed]

C. Mu, Z. Zhang, M. Lin, X. Cao, B. R. Watts, and C.-Q. Xu, “Strong fluidic interconnections for optofluidic devices” (submitted toSens. Actuators B).

Zhao, P.

Z. Zhang, P. Zhao, G. Xiao, B. R. Watts, and C.-Q. Xu, “Sealing SU-8 microfluidic channels using PDMS,” Biomicrofluidics5(4), 046503 (2011).
[CrossRef] [PubMed]

Zhao, Y.

X. Mao, A. A. Nawaz, S.-C. S. Lin, M. I. Lapsley, Y. Zhao, J. P. McCoy, W. S. El-Deiry, and T. J. Huang, “An integrated, multiparametric flow cytometry chip using ‘microfluidic drifting’ based three-dimensional hydrodynamic focusing,” Biomicrofluidics6(2), 024113 (2012).
[CrossRef] [PubMed]

Zhu, S.

B. R. Watts, T. Kowpak, Z. Zhang, C.-Q. Xu, S. Zhu, X. Cao, and M. Lin, “Fabrication and performance of a photonic-microfluidic integrated device,” Micromachines3(4), 62–77 (2012).
[CrossRef]

T. Kowpak, B. R. Watts, Z. Zhang, S. Zhu, and C.-Q. Xu, “Fabrication of photonic/microfluidic integrated devices using an epoxy photoresist,” Macromol. Mater. Eng.295(6), 559–565 (2010).
[CrossRef]

B. R. Watts, T. Kowpak, Z. Zhang, C. Q. Xu, and S. Zhu, “Formation and characterization of an ideal excitation beam geometry in an optofluidic device,” Biomed. Opt. Express1(3), 848–860 (2010).
[CrossRef] [PubMed]

Adv. Drug Deliv. Rev. (1)

W. G. Lee, Y.-G. Kim, B. G. Chung, U. Demirci, and A. Khademhosseini, “Nano/microfluidics for diagnosis of infectious diseases in developing countries,” Adv. Drug Deliv. Rev.62(4-5), 449–457 (2010).
[CrossRef] [PubMed]

Anal. Bioanal. Chem. (1)

D. A. Ateya, J. S. Erickson, P. B. Howell, L. R. Hilliard, J. P. Golden, and F. S. Ligler, “The good, the bad, and the tiny: a review of microflow cytometry,” Anal. Bioanal. Chem.391(5), 1485–1498 (2008).
[CrossRef] [PubMed]

Annu. Rev. Mater. Sci. (1)

Y. Xia and G. M. Whitesides, “Soft lithography,” Annu. Rev. Mater. Sci.28(1), 153–184 (1998).
[CrossRef]

Annu. Rev. Public Health (1)

B. H. Robertson and J. K. A. Nicholson, “New microbiology tools for public health and their implications,” Annu. Rev. Public Health26(1), 281–302 (2005).
[CrossRef] [PubMed]

Appl. Opt. (1)

Biomed. Opt. Express (3)

Biomicrofluidics (4)

X. Mao, A. A. Nawaz, S.-C. S. Lin, M. I. Lapsley, Y. Zhao, J. P. McCoy, W. S. El-Deiry, and T. J. Huang, “An integrated, multiparametric flow cytometry chip using ‘microfluidic drifting’ based three-dimensional hydrodynamic focusing,” Biomicrofluidics6(2), 024113 (2012).
[CrossRef] [PubMed]

Z. Zhang, P. Zhao, G. Xiao, B. R. Watts, and C.-Q. Xu, “Sealing SU-8 microfluidic channels using PDMS,” Biomicrofluidics5(4), 046503 (2011).
[CrossRef] [PubMed]

S. H. Cho, J. M. Godin, C.-H. Chen, W. Qiao, H. Lee, and Y.-H. Lo, “Review article: recent advancements in optofluidic flow cytometer,” Biomicrofluidics4(4), 043001 (2010).
[CrossRef] [PubMed]

M. Rosenauer and M. J. Vellekoop, “Characterization of a microflow cytometer with an integrated three-dimensional optofluidic lens system,” Biomicrofluidics4(4), 043005 (2010).
[CrossRef] [PubMed]

Biosens. Bioelectron. (1)

N. Hashemi, J. S. Erickson, J. P. Golden, K. M. Jackson, and F. S. Ligler, “Microflow cytometer for optical analysis of phytoplankton,” Biosens. Bioelectron.26(11), 4263–4269 (2011).
[CrossRef] [PubMed]

Cytometry A (1)

M. Frankowski, N. Bock, A. Kummrow, S. Schädel-Ebner, M. Schmidt, A. Tuchscheerer, and J. Neukammer, “A microflow cytometer exploited for the immunological differentiation of leukocytes,” Cytometry A79A(8), 613–624 (2011).
[CrossRef] [PubMed]

Electrophoresis (2)

T. D. Chung and H. C. Kim, “Recent advances in miniaturized microfluidic flow cytometry for clinical use,” Electrophoresis28(24), 4511–4520 (2007).
[CrossRef] [PubMed]

B. R. Watts, Z. Zhang, C.-Q. Xu, X. Cao, and M. Lin, “A photonic-microfluidic integrated device for reliable fluorescence detection and counting,” Electrophoresis33(21), 3236–3244 (2012).
[CrossRef] [PubMed]

Extremophiles (1)

P. L. Bergquist, E. M. Hardiman, B. C. Ferrari, and T. Winsley, “Applications of flow cytometry in environmental microbiology and biotechnology,” Extremophiles13(3), 389–401 (2009).
[CrossRef] [PubMed]

J. Assoc. Lab. Autom. (1)

D. Heikali and D. Di Carlo, “A niche for microfluidics in portable hematology analyzers,” J. Assoc. Lab. Autom.15(4), 319–328 (2010).
[CrossRef]

J. Health Sci. (1)

M. Ikeda, N. Yamaguchi, and M. Nasu, “Rapid on-chip flow cytometric detection of Listeria monocytogenes in milk,” J. Health Sci.55(5), 851–856 (2009).
[CrossRef]

Lab Chip (1)

P. Fei, Z. Chen, Y. Men, A. Li, Y. Shen, and Y. Huang, “A compact optofluidic cytometer with integrated liquid-core/PDMS-cladding waveguides,” Lab Chip12(19), 3700–3706 (2012).
[CrossRef] [PubMed]

Macromol. Mater. Eng. (1)

T. Kowpak, B. R. Watts, Z. Zhang, S. Zhu, and C.-Q. Xu, “Fabrication of photonic/microfluidic integrated devices using an epoxy photoresist,” Macromol. Mater. Eng.295(6), 559–565 (2010).
[CrossRef]

Microfluid. Nanofluid. (1)

M. Rosenauer, W. Buchegger, I. Finoulst, P. Verhaert, and M. Vellekoop, “Miniaturized flow cytometer with 3D hydrodynamic particle focusing and integrated optical elements applying silicon photodiodes,” Microfluid. Nanofluid.10(4), 761–771 (2011).
[CrossRef]

Micromachines (1)

B. R. Watts, T. Kowpak, Z. Zhang, C.-Q. Xu, S. Zhu, X. Cao, and M. Lin, “Fabrication and performance of a photonic-microfluidic integrated device,” Micromachines3(4), 62–77 (2012).
[CrossRef]

Physiol. Meas. (1)

D. Huh, W. Gu, Y. Kamotani, J. B. Grotberg, and S. Takayama, “Microfluidics for flow cytometric analysis of cells and particles,” Physiol. Meas.26(3), R73–R98 (2005).
[CrossRef] [PubMed]

Sens. Actuators B (1)

C. Mu, Z. Zhang, M. Lin, X. Cao, B. R. Watts, and C.-Q. Xu, “Strong fluidic interconnections for optofluidic devices” (submitted toSens. Actuators B).

Trends Biotechnol. (1)

D. S. Boyle, K. R. Hawkins, M. S. Steele, M. Singhal, and X. Cheng, “Emerging technologies for point-of-care CD4 T-lymphocyte counting,” Trends Biotechnol.30(1), 45–54 (2012).
[CrossRef] [PubMed]

Other (2)

H. M. Shapiro, Practical Flow Cytometry (John Wiley & Sons, 2003).

B. R. Watts (Department of Engineering Physics, McMaster University, Hamilton, Ontario L8S 4L7, Canada) is preparing a manuscript titled “Scattering detection using a photonic-microfluidic integrated device with on-chip collection capabilities”.

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Figures (6)

Fig. 1
Fig. 1

a) A particle in a focused beam has the forward scattered light masked by transmitted light from other divergent rays. b) Conventional techniques insert a field stop in the incoming light to ensure a dark field in the image space where collection takes place [15].

Fig. 2
Fig. 2

a) Picture showing a planar device with on-chip waveguides to collect scattered light showing that a forward scatter waveguide collects transmitted light. b) Graph showing 200ms of raw data from a simultaneous free-space and on-chip scatter detection and showing poor SNR from the forward scatter from a simple on-chip waveguide – detection algorithms will miss such events.

Fig. 3
Fig. 3

a) Simulation results showing the function of the notch at the lens surface as it deflects central rays away while leaving far radial rays intact. b) simulation of the notch in the lens system and the image plane of surface two with a hole burned in the image from the notch (physical drawing of notch omitted for clarity).

Fig. 4
Fig. 4

Pictures of the fabricated device: a) SEM image of the lens system with notch, b) packaged device, c) photomask design of the device showing the microfluidics integrated with the optical interrogation scheme.

Fig. 5
Fig. 5

a) Raw data from 50ms of bead flow showing bursts from forward scatter light collected on-chip using the new designs showing clear identifiable bursts, b) histogram from the on-chip scatter detection.

Fig. 6
Fig. 6

Simultaneous free-space side and on-chip forward scatter detection. a) Plot of raw data showing the simultaneous bursts. b) Scatter plot of on-chip and free-space data showing an excellent correlation between events, including the double detections, missed events, and noise events.

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