Abstract

We demonstrate the use of a compressive sampling algorithm for on-chip fluorescent imaging of sparse objects over an ultra-large field-of-view (>8 cm2) without the need for any lenses or mechanical scanning. In this lensfree imaging technique, fluorescent samples placed on a chip are excited through a prism interface, where the pump light is filtered out by total internal reflection after exciting the entire sample volume. The emitted fluorescent light from the specimen is collected through an on-chip fiber-optic faceplate and is delivered to a wide field-of-view opto-electronic sensor array for lensless recording of fluorescent spots corresponding to the samples. A compressive sampling based optimization algorithm is then used to rapidly reconstruct the sparse distribution of fluorescent sources to achieve ~10 µm spatial resolution over the entire active region of the sensor-array, i.e., over an imaging field-of-view of >8 cm2. Such a wide-field lensless fluorescent imaging platform could especially be significant for high-throughput imaging cytometry, rare cell analysis, as well as for micro-array research.

© 2010 OSA

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2010

2009

S. Seo, T. W. Su, D. K. Tseng, A. Erlinger, and A. Ozcan, “Lensfree holographic imaging for on-chip cytometry and diagnostics,” Lab Chip 9(6), 777–787 (2009).
[CrossRef] [PubMed]

S. J. Tan, L. Yobas, G. Y. H. Lee, C. N. Ong, and C. T. Lim, “Microdevice for the isolation and enumeration of cancer cells from blood,” Biomed. Microdevices 11(4), 883 (2009).
[CrossRef] [PubMed]

D. J. Brady, K. Choi, D. L. Marks, R. Horisaki, and S. Lim, “Compressive holography,” Opt. Express 17(15), 13040–13049 (2009).
[CrossRef] [PubMed]

L. Denis, D. Lorenz, E. Thiébaut, C. Fournier, and D. Trede, “Inline hologram reconstruction with sparsity constraints,” Opt. Lett. 34(22), 3475–3477 (2009).
[CrossRef] [PubMed]

H. Yu and G. Wang, “Compressed sensing based interior tomography,” Phys. Med. Biol. 54(9), 2791–2805 (2009).
[CrossRef] [PubMed]

Y. Lu, X. Zhang, A. Douraghy, D. Stout, J. Tian, T. F. Chan, and A. F. Chatziioannou, “Source reconstruction for spectrally-resolved bioluminescence tomography with sparse a priori information,” Opt. Express 17(10), 8062–8080 (2009).
[CrossRef] [PubMed]

2008

M. F. Duarte, M. A. Davenport, D. Takhar, J. N. Laska, K. F. Ting Sun, Kelly, and R. G. Baraniuk, “Single-pixel imaging via compressive sampling,” IEEE Signal Process. Mag. 25(2), 83–91 (2008).
[CrossRef]

A. Wagadarikar, R. John, R. Willett, and D. J. Brady, “Single disperser design for coded aperture snapshot spectral imaging,” Appl. Opt. 47(10), B44–B51 (2008).
[CrossRef] [PubMed]

W. L. Chan, M. L. Moravec, R. G. Baraniuk, and D. M. Mittleman, “Terahertz imaging with compressed sensing and phase retrieval,” Opt. Lett. 33(9), 974–976 (2008).
[CrossRef] [PubMed]

J. Romberg, “Imaging via Compressive Sampling,” IEEE Signal Process. Mag. 25(2), 14–20 (2008).
[CrossRef]

A. A. Adams, P. I. Okagbare, J. Feng, M. L. Hupert, D. Patterson, J. Göttert, R. L. McCarley, D. Nikitopoulos, M. C. Murphy, and S. A. Soper, “Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor,” J. Am. Chem. Soc. 130(27), 8633–8641 (2008).
[CrossRef] [PubMed]

2007

S.-J. Kim, K. Koh, M. Lustig, S. Boyd, and D. Gorinevsky, “An Interior-Point Method for Large-Scale l1-Regularized Least Squares,” IEEE J. Sel. Top. Signal Processing 1(4), 606–617 (2007).
[CrossRef]

M. Lustig, D. Donoho, and J. M. Pauly, “Sparse MRI: The application of compressed sensing for rapid MR imaging,” Magn. Reson. Med. 58(6), 1182–1195 (2007).
[CrossRef] [PubMed]

M. E. Gehm, R. John, D. J. Brady, R. M. Willett, and T. J. Schulz, “Single-shot compressive spectral imaging with a dual-disperser architecture,” Opt. Express 15(21), 14013–14027 (2007).
[CrossRef] [PubMed]

S. Nagrath, L. V. Sequist, S. Maheswaran, D. W. Bell, D. Irimia, L. Ulkus, M. R. Smith, E. L. Kwak, S. Digumarthy, A. Muzikansky, P. Ryan, U. J. Balis, R. G. Tompkins, D. A. Haber, and M. Toner, “Isolation of rare circulating tumour cells in cancer patients by microchip technology,” Nature 450(7173), 1235–1239 (2007).
[CrossRef] [PubMed]

2006

E. J. Candès, J. K. Romberg, and T. Tao, “Stable signal recovery from incomplete and inaccurate measurements,” Commun. Pure Appl. Math. 59(8), 1207–1223 (2006).
[CrossRef]

E. J. Candes and T. Tao, “Near-optimal signal recovery from random projections: Universal encoding strategies?” IEEE Trans. Inf. Theory 52(12), 5406–5425 (2006).
[CrossRef]

D. L. Donoho, “Compressed sensing,” IEEE Trans. Inf. Theory 52(4), 1289–1306 (2006).
[CrossRef]

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313(5793), 1642–1645 (2006).
[CrossRef] [PubMed]

M. J. Rust, M. Bates, and X. Zhuang, “Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM),” Nat. Methods 3(10), 793–796 (2006).
[CrossRef] [PubMed]

2004

S. K. Murthy, A. Sin, R. G. Tompkins, and M. Toner, “Effect of flow and surface conditions on human lymphocyte isolation using microfluidic chambers,” Langmuir 20(26), 11649–11655 (2004).
[CrossRef] [PubMed]

1997

1974

L. B. Lucy, “An iterative technique for the rectification of observed distributions,” Astron. J. 79, 745–754 (1974).
[CrossRef]

1972

Adams, A. A.

A. A. Adams, P. I. Okagbare, J. Feng, M. L. Hupert, D. Patterson, J. Göttert, R. L. McCarley, D. Nikitopoulos, M. C. Murphy, and S. A. Soper, “Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor,” J. Am. Chem. Soc. 130(27), 8633–8641 (2008).
[CrossRef] [PubMed]

Andrews, M.

Balis, U. J.

S. Nagrath, L. V. Sequist, S. Maheswaran, D. W. Bell, D. Irimia, L. Ulkus, M. R. Smith, E. L. Kwak, S. Digumarthy, A. Muzikansky, P. Ryan, U. J. Balis, R. G. Tompkins, D. A. Haber, and M. Toner, “Isolation of rare circulating tumour cells in cancer patients by microchip technology,” Nature 450(7173), 1235–1239 (2007).
[CrossRef] [PubMed]

Baraniuk, R. G.

M. F. Duarte, M. A. Davenport, D. Takhar, J. N. Laska, K. F. Ting Sun, Kelly, and R. G. Baraniuk, “Single-pixel imaging via compressive sampling,” IEEE Signal Process. Mag. 25(2), 83–91 (2008).
[CrossRef]

W. L. Chan, M. L. Moravec, R. G. Baraniuk, and D. M. Mittleman, “Terahertz imaging with compressed sensing and phase retrieval,” Opt. Lett. 33(9), 974–976 (2008).
[CrossRef] [PubMed]

Bates, M.

M. J. Rust, M. Bates, and X. Zhuang, “Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM),” Nat. Methods 3(10), 793–796 (2006).
[CrossRef] [PubMed]

Bell, D. W.

S. Nagrath, L. V. Sequist, S. Maheswaran, D. W. Bell, D. Irimia, L. Ulkus, M. R. Smith, E. L. Kwak, S. Digumarthy, A. Muzikansky, P. Ryan, U. J. Balis, R. G. Tompkins, D. A. Haber, and M. Toner, “Isolation of rare circulating tumour cells in cancer patients by microchip technology,” Nature 450(7173), 1235–1239 (2007).
[CrossRef] [PubMed]

Betzig, E.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313(5793), 1642–1645 (2006).
[CrossRef] [PubMed]

Biggs, D. S. C.

Bonifacino, J. S.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313(5793), 1642–1645 (2006).
[CrossRef] [PubMed]

Boyd, S.

S.-J. Kim, K. Koh, M. Lustig, S. Boyd, and D. Gorinevsky, “An Interior-Point Method for Large-Scale l1-Regularized Least Squares,” IEEE J. Sel. Top. Signal Processing 1(4), 606–617 (2007).
[CrossRef]

Brady, D. J.

Candes, E. J.

E. J. Candes and T. Tao, “Near-optimal signal recovery from random projections: Universal encoding strategies?” IEEE Trans. Inf. Theory 52(12), 5406–5425 (2006).
[CrossRef]

Candès, E. J.

E. J. Candès, J. K. Romberg, and T. Tao, “Stable signal recovery from incomplete and inaccurate measurements,” Commun. Pure Appl. Math. 59(8), 1207–1223 (2006).
[CrossRef]

Chan, T. F.

Chan, W. L.

Chatziioannou, A. F.

Choi, K.

Coskun, A. F.

A. F. Coskun, T. W. Su, and A. Ozcan, “Wide field-of-view lens-free fluorescent imaging on a chip,” Lab Chip 10(7), 824–827 (2010).
[CrossRef] [PubMed]

Davenport, M. A.

M. F. Duarte, M. A. Davenport, D. Takhar, J. N. Laska, K. F. Ting Sun, Kelly, and R. G. Baraniuk, “Single-pixel imaging via compressive sampling,” IEEE Signal Process. Mag. 25(2), 83–91 (2008).
[CrossRef]

Davidson, M. W.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313(5793), 1642–1645 (2006).
[CrossRef] [PubMed]

Denis, L.

Digumarthy, S.

S. Nagrath, L. V. Sequist, S. Maheswaran, D. W. Bell, D. Irimia, L. Ulkus, M. R. Smith, E. L. Kwak, S. Digumarthy, A. Muzikansky, P. Ryan, U. J. Balis, R. G. Tompkins, D. A. Haber, and M. Toner, “Isolation of rare circulating tumour cells in cancer patients by microchip technology,” Nature 450(7173), 1235–1239 (2007).
[CrossRef] [PubMed]

Donoho, D.

M. Lustig, D. Donoho, and J. M. Pauly, “Sparse MRI: The application of compressed sensing for rapid MR imaging,” Magn. Reson. Med. 58(6), 1182–1195 (2007).
[CrossRef] [PubMed]

Donoho, D. L.

D. L. Donoho, “Compressed sensing,” IEEE Trans. Inf. Theory 52(4), 1289–1306 (2006).
[CrossRef]

Douraghy, A.

Duarte, M. F.

M. F. Duarte, M. A. Davenport, D. Takhar, J. N. Laska, K. F. Ting Sun, Kelly, and R. G. Baraniuk, “Single-pixel imaging via compressive sampling,” IEEE Signal Process. Mag. 25(2), 83–91 (2008).
[CrossRef]

Erlinger, A.

S. Seo, T. W. Su, D. K. Tseng, A. Erlinger, and A. Ozcan, “Lensfree holographic imaging for on-chip cytometry and diagnostics,” Lab Chip 9(6), 777–787 (2009).
[CrossRef] [PubMed]

Feng, J.

A. A. Adams, P. I. Okagbare, J. Feng, M. L. Hupert, D. Patterson, J. Göttert, R. L. McCarley, D. Nikitopoulos, M. C. Murphy, and S. A. Soper, “Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor,” J. Am. Chem. Soc. 130(27), 8633–8641 (2008).
[CrossRef] [PubMed]

Fournier, C.

Gao, H.

Gehm, M. E.

Gorinevsky, D.

S.-J. Kim, K. Koh, M. Lustig, S. Boyd, and D. Gorinevsky, “An Interior-Point Method for Large-Scale l1-Regularized Least Squares,” IEEE J. Sel. Top. Signal Processing 1(4), 606–617 (2007).
[CrossRef]

Göttert, J.

A. A. Adams, P. I. Okagbare, J. Feng, M. L. Hupert, D. Patterson, J. Göttert, R. L. McCarley, D. Nikitopoulos, M. C. Murphy, and S. A. Soper, “Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor,” J. Am. Chem. Soc. 130(27), 8633–8641 (2008).
[CrossRef] [PubMed]

Haber, D. A.

S. Nagrath, L. V. Sequist, S. Maheswaran, D. W. Bell, D. Irimia, L. Ulkus, M. R. Smith, E. L. Kwak, S. Digumarthy, A. Muzikansky, P. Ryan, U. J. Balis, R. G. Tompkins, D. A. Haber, and M. Toner, “Isolation of rare circulating tumour cells in cancer patients by microchip technology,” Nature 450(7173), 1235–1239 (2007).
[CrossRef] [PubMed]

Hess, H. F.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313(5793), 1642–1645 (2006).
[CrossRef] [PubMed]

Horisaki, R.

Hupert, M. L.

A. A. Adams, P. I. Okagbare, J. Feng, M. L. Hupert, D. Patterson, J. Göttert, R. L. McCarley, D. Nikitopoulos, M. C. Murphy, and S. A. Soper, “Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor,” J. Am. Chem. Soc. 130(27), 8633–8641 (2008).
[CrossRef] [PubMed]

Irimia, D.

S. Nagrath, L. V. Sequist, S. Maheswaran, D. W. Bell, D. Irimia, L. Ulkus, M. R. Smith, E. L. Kwak, S. Digumarthy, A. Muzikansky, P. Ryan, U. J. Balis, R. G. Tompkins, D. A. Haber, and M. Toner, “Isolation of rare circulating tumour cells in cancer patients by microchip technology,” Nature 450(7173), 1235–1239 (2007).
[CrossRef] [PubMed]

Isikman, S. O.

John, R.

Kelly,

M. F. Duarte, M. A. Davenport, D. Takhar, J. N. Laska, K. F. Ting Sun, Kelly, and R. G. Baraniuk, “Single-pixel imaging via compressive sampling,” IEEE Signal Process. Mag. 25(2), 83–91 (2008).
[CrossRef]

Khademhosseinieh, B.

Kim, S.-J.

S.-J. Kim, K. Koh, M. Lustig, S. Boyd, and D. Gorinevsky, “An Interior-Point Method for Large-Scale l1-Regularized Least Squares,” IEEE J. Sel. Top. Signal Processing 1(4), 606–617 (2007).
[CrossRef]

Koh, K.

S.-J. Kim, K. Koh, M. Lustig, S. Boyd, and D. Gorinevsky, “An Interior-Point Method for Large-Scale l1-Regularized Least Squares,” IEEE J. Sel. Top. Signal Processing 1(4), 606–617 (2007).
[CrossRef]

Kwak, E. L.

S. Nagrath, L. V. Sequist, S. Maheswaran, D. W. Bell, D. Irimia, L. Ulkus, M. R. Smith, E. L. Kwak, S. Digumarthy, A. Muzikansky, P. Ryan, U. J. Balis, R. G. Tompkins, D. A. Haber, and M. Toner, “Isolation of rare circulating tumour cells in cancer patients by microchip technology,” Nature 450(7173), 1235–1239 (2007).
[CrossRef] [PubMed]

Laska, J. N.

M. F. Duarte, M. A. Davenport, D. Takhar, J. N. Laska, K. F. Ting Sun, Kelly, and R. G. Baraniuk, “Single-pixel imaging via compressive sampling,” IEEE Signal Process. Mag. 25(2), 83–91 (2008).
[CrossRef]

Lee, G. Y. H.

S. J. Tan, L. Yobas, G. Y. H. Lee, C. N. Ong, and C. T. Lim, “Microdevice for the isolation and enumeration of cancer cells from blood,” Biomed. Microdevices 11(4), 883 (2009).
[CrossRef] [PubMed]

Lim, C. T.

S. J. Tan, L. Yobas, G. Y. H. Lee, C. N. Ong, and C. T. Lim, “Microdevice for the isolation and enumeration of cancer cells from blood,” Biomed. Microdevices 11(4), 883 (2009).
[CrossRef] [PubMed]

Lim, S.

Lindwasser, O. W.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313(5793), 1642–1645 (2006).
[CrossRef] [PubMed]

Lippincott-Schwartz, J.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313(5793), 1642–1645 (2006).
[CrossRef] [PubMed]

Lorenz, D.

Lu, Y.

Lucy, L. B.

L. B. Lucy, “An iterative technique for the rectification of observed distributions,” Astron. J. 79, 745–754 (1974).
[CrossRef]

Lustig, M.

S.-J. Kim, K. Koh, M. Lustig, S. Boyd, and D. Gorinevsky, “An Interior-Point Method for Large-Scale l1-Regularized Least Squares,” IEEE J. Sel. Top. Signal Processing 1(4), 606–617 (2007).
[CrossRef]

M. Lustig, D. Donoho, and J. M. Pauly, “Sparse MRI: The application of compressed sensing for rapid MR imaging,” Magn. Reson. Med. 58(6), 1182–1195 (2007).
[CrossRef] [PubMed]

Maheswaran, S.

S. Nagrath, L. V. Sequist, S. Maheswaran, D. W. Bell, D. Irimia, L. Ulkus, M. R. Smith, E. L. Kwak, S. Digumarthy, A. Muzikansky, P. Ryan, U. J. Balis, R. G. Tompkins, D. A. Haber, and M. Toner, “Isolation of rare circulating tumour cells in cancer patients by microchip technology,” Nature 450(7173), 1235–1239 (2007).
[CrossRef] [PubMed]

Marks, D. L.

McCarley, R. L.

A. A. Adams, P. I. Okagbare, J. Feng, M. L. Hupert, D. Patterson, J. Göttert, R. L. McCarley, D. Nikitopoulos, M. C. Murphy, and S. A. Soper, “Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor,” J. Am. Chem. Soc. 130(27), 8633–8641 (2008).
[CrossRef] [PubMed]

Mittleman, D. M.

Moravec, M. L.

Murphy, M. C.

A. A. Adams, P. I. Okagbare, J. Feng, M. L. Hupert, D. Patterson, J. Göttert, R. L. McCarley, D. Nikitopoulos, M. C. Murphy, and S. A. Soper, “Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor,” J. Am. Chem. Soc. 130(27), 8633–8641 (2008).
[CrossRef] [PubMed]

Murthy, S. K.

S. K. Murthy, A. Sin, R. G. Tompkins, and M. Toner, “Effect of flow and surface conditions on human lymphocyte isolation using microfluidic chambers,” Langmuir 20(26), 11649–11655 (2004).
[CrossRef] [PubMed]

Muzikansky, A.

S. Nagrath, L. V. Sequist, S. Maheswaran, D. W. Bell, D. Irimia, L. Ulkus, M. R. Smith, E. L. Kwak, S. Digumarthy, A. Muzikansky, P. Ryan, U. J. Balis, R. G. Tompkins, D. A. Haber, and M. Toner, “Isolation of rare circulating tumour cells in cancer patients by microchip technology,” Nature 450(7173), 1235–1239 (2007).
[CrossRef] [PubMed]

Nagrath, S.

S. Nagrath, L. V. Sequist, S. Maheswaran, D. W. Bell, D. Irimia, L. Ulkus, M. R. Smith, E. L. Kwak, S. Digumarthy, A. Muzikansky, P. Ryan, U. J. Balis, R. G. Tompkins, D. A. Haber, and M. Toner, “Isolation of rare circulating tumour cells in cancer patients by microchip technology,” Nature 450(7173), 1235–1239 (2007).
[CrossRef] [PubMed]

Nikitopoulos, D.

A. A. Adams, P. I. Okagbare, J. Feng, M. L. Hupert, D. Patterson, J. Göttert, R. L. McCarley, D. Nikitopoulos, M. C. Murphy, and S. A. Soper, “Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor,” J. Am. Chem. Soc. 130(27), 8633–8641 (2008).
[CrossRef] [PubMed]

Oh, C.

Okagbare, P. I.

A. A. Adams, P. I. Okagbare, J. Feng, M. L. Hupert, D. Patterson, J. Göttert, R. L. McCarley, D. Nikitopoulos, M. C. Murphy, and S. A. Soper, “Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor,” J. Am. Chem. Soc. 130(27), 8633–8641 (2008).
[CrossRef] [PubMed]

Olenych, S.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313(5793), 1642–1645 (2006).
[CrossRef] [PubMed]

Ong, C. N.

S. J. Tan, L. Yobas, G. Y. H. Lee, C. N. Ong, and C. T. Lim, “Microdevice for the isolation and enumeration of cancer cells from blood,” Biomed. Microdevices 11(4), 883 (2009).
[CrossRef] [PubMed]

Ozcan, A.

C. Oh, S. O. Isikman, B. Khademhosseinieh, and A. Ozcan, “On-chip differential interference contrast microscopy using lensless digital holography,” Opt. Express 18(5Issue 5), 4717–4726 (2010).
[CrossRef] [PubMed]

A. F. Coskun, T. W. Su, and A. Ozcan, “Wide field-of-view lens-free fluorescent imaging on a chip,” Lab Chip 10(7), 824–827 (2010).
[CrossRef] [PubMed]

S. Seo, T. W. Su, D. K. Tseng, A. Erlinger, and A. Ozcan, “Lensfree holographic imaging for on-chip cytometry and diagnostics,” Lab Chip 9(6), 777–787 (2009).
[CrossRef] [PubMed]

Patterson, D.

A. A. Adams, P. I. Okagbare, J. Feng, M. L. Hupert, D. Patterson, J. Göttert, R. L. McCarley, D. Nikitopoulos, M. C. Murphy, and S. A. Soper, “Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor,” J. Am. Chem. Soc. 130(27), 8633–8641 (2008).
[CrossRef] [PubMed]

Patterson, G. H.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313(5793), 1642–1645 (2006).
[CrossRef] [PubMed]

Pauly, J. M.

M. Lustig, D. Donoho, and J. M. Pauly, “Sparse MRI: The application of compressed sensing for rapid MR imaging,” Magn. Reson. Med. 58(6), 1182–1195 (2007).
[CrossRef] [PubMed]

Richardson, W. H.

Romberg, J.

J. Romberg, “Imaging via Compressive Sampling,” IEEE Signal Process. Mag. 25(2), 14–20 (2008).
[CrossRef]

Romberg, J. K.

E. J. Candès, J. K. Romberg, and T. Tao, “Stable signal recovery from incomplete and inaccurate measurements,” Commun. Pure Appl. Math. 59(8), 1207–1223 (2006).
[CrossRef]

Rust, M. J.

M. J. Rust, M. Bates, and X. Zhuang, “Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM),” Nat. Methods 3(10), 793–796 (2006).
[CrossRef] [PubMed]

Ryan, P.

S. Nagrath, L. V. Sequist, S. Maheswaran, D. W. Bell, D. Irimia, L. Ulkus, M. R. Smith, E. L. Kwak, S. Digumarthy, A. Muzikansky, P. Ryan, U. J. Balis, R. G. Tompkins, D. A. Haber, and M. Toner, “Isolation of rare circulating tumour cells in cancer patients by microchip technology,” Nature 450(7173), 1235–1239 (2007).
[CrossRef] [PubMed]

Schulz, T. J.

Seo, S.

S. Seo, T. W. Su, D. K. Tseng, A. Erlinger, and A. Ozcan, “Lensfree holographic imaging for on-chip cytometry and diagnostics,” Lab Chip 9(6), 777–787 (2009).
[CrossRef] [PubMed]

Sequist, L. V.

S. Nagrath, L. V. Sequist, S. Maheswaran, D. W. Bell, D. Irimia, L. Ulkus, M. R. Smith, E. L. Kwak, S. Digumarthy, A. Muzikansky, P. Ryan, U. J. Balis, R. G. Tompkins, D. A. Haber, and M. Toner, “Isolation of rare circulating tumour cells in cancer patients by microchip technology,” Nature 450(7173), 1235–1239 (2007).
[CrossRef] [PubMed]

Sin, A.

S. K. Murthy, A. Sin, R. G. Tompkins, and M. Toner, “Effect of flow and surface conditions on human lymphocyte isolation using microfluidic chambers,” Langmuir 20(26), 11649–11655 (2004).
[CrossRef] [PubMed]

Smith, M. R.

S. Nagrath, L. V. Sequist, S. Maheswaran, D. W. Bell, D. Irimia, L. Ulkus, M. R. Smith, E. L. Kwak, S. Digumarthy, A. Muzikansky, P. Ryan, U. J. Balis, R. G. Tompkins, D. A. Haber, and M. Toner, “Isolation of rare circulating tumour cells in cancer patients by microchip technology,” Nature 450(7173), 1235–1239 (2007).
[CrossRef] [PubMed]

Soper, S. A.

A. A. Adams, P. I. Okagbare, J. Feng, M. L. Hupert, D. Patterson, J. Göttert, R. L. McCarley, D. Nikitopoulos, M. C. Murphy, and S. A. Soper, “Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor,” J. Am. Chem. Soc. 130(27), 8633–8641 (2008).
[CrossRef] [PubMed]

Sougrat, R.

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313(5793), 1642–1645 (2006).
[CrossRef] [PubMed]

Stout, D.

Su, T. W.

A. F. Coskun, T. W. Su, and A. Ozcan, “Wide field-of-view lens-free fluorescent imaging on a chip,” Lab Chip 10(7), 824–827 (2010).
[CrossRef] [PubMed]

S. Seo, T. W. Su, D. K. Tseng, A. Erlinger, and A. Ozcan, “Lensfree holographic imaging for on-chip cytometry and diagnostics,” Lab Chip 9(6), 777–787 (2009).
[CrossRef] [PubMed]

Takhar, D.

M. F. Duarte, M. A. Davenport, D. Takhar, J. N. Laska, K. F. Ting Sun, Kelly, and R. G. Baraniuk, “Single-pixel imaging via compressive sampling,” IEEE Signal Process. Mag. 25(2), 83–91 (2008).
[CrossRef]

Tan, S. J.

S. J. Tan, L. Yobas, G. Y. H. Lee, C. N. Ong, and C. T. Lim, “Microdevice for the isolation and enumeration of cancer cells from blood,” Biomed. Microdevices 11(4), 883 (2009).
[CrossRef] [PubMed]

Tao, T.

E. J. Candès, J. K. Romberg, and T. Tao, “Stable signal recovery from incomplete and inaccurate measurements,” Commun. Pure Appl. Math. 59(8), 1207–1223 (2006).
[CrossRef]

E. J. Candes and T. Tao, “Near-optimal signal recovery from random projections: Universal encoding strategies?” IEEE Trans. Inf. Theory 52(12), 5406–5425 (2006).
[CrossRef]

Thiébaut, E.

Tian, J.

Ting Sun, K. F.

M. F. Duarte, M. A. Davenport, D. Takhar, J. N. Laska, K. F. Ting Sun, Kelly, and R. G. Baraniuk, “Single-pixel imaging via compressive sampling,” IEEE Signal Process. Mag. 25(2), 83–91 (2008).
[CrossRef]

Tompkins, R. G.

S. Nagrath, L. V. Sequist, S. Maheswaran, D. W. Bell, D. Irimia, L. Ulkus, M. R. Smith, E. L. Kwak, S. Digumarthy, A. Muzikansky, P. Ryan, U. J. Balis, R. G. Tompkins, D. A. Haber, and M. Toner, “Isolation of rare circulating tumour cells in cancer patients by microchip technology,” Nature 450(7173), 1235–1239 (2007).
[CrossRef] [PubMed]

S. K. Murthy, A. Sin, R. G. Tompkins, and M. Toner, “Effect of flow and surface conditions on human lymphocyte isolation using microfluidic chambers,” Langmuir 20(26), 11649–11655 (2004).
[CrossRef] [PubMed]

Toner, M.

S. Nagrath, L. V. Sequist, S. Maheswaran, D. W. Bell, D. Irimia, L. Ulkus, M. R. Smith, E. L. Kwak, S. Digumarthy, A. Muzikansky, P. Ryan, U. J. Balis, R. G. Tompkins, D. A. Haber, and M. Toner, “Isolation of rare circulating tumour cells in cancer patients by microchip technology,” Nature 450(7173), 1235–1239 (2007).
[CrossRef] [PubMed]

S. K. Murthy, A. Sin, R. G. Tompkins, and M. Toner, “Effect of flow and surface conditions on human lymphocyte isolation using microfluidic chambers,” Langmuir 20(26), 11649–11655 (2004).
[CrossRef] [PubMed]

Trede, D.

Tseng, D. K.

S. Seo, T. W. Su, D. K. Tseng, A. Erlinger, and A. Ozcan, “Lensfree holographic imaging for on-chip cytometry and diagnostics,” Lab Chip 9(6), 777–787 (2009).
[CrossRef] [PubMed]

Ulkus, L.

S. Nagrath, L. V. Sequist, S. Maheswaran, D. W. Bell, D. Irimia, L. Ulkus, M. R. Smith, E. L. Kwak, S. Digumarthy, A. Muzikansky, P. Ryan, U. J. Balis, R. G. Tompkins, D. A. Haber, and M. Toner, “Isolation of rare circulating tumour cells in cancer patients by microchip technology,” Nature 450(7173), 1235–1239 (2007).
[CrossRef] [PubMed]

Wagadarikar, A.

Wang, G.

H. Yu and G. Wang, “Compressed sensing based interior tomography,” Phys. Med. Biol. 54(9), 2791–2805 (2009).
[CrossRef] [PubMed]

Willett, R.

Willett, R. M.

Yobas, L.

S. J. Tan, L. Yobas, G. Y. H. Lee, C. N. Ong, and C. T. Lim, “Microdevice for the isolation and enumeration of cancer cells from blood,” Biomed. Microdevices 11(4), 883 (2009).
[CrossRef] [PubMed]

Yu, H.

H. Yu and G. Wang, “Compressed sensing based interior tomography,” Phys. Med. Biol. 54(9), 2791–2805 (2009).
[CrossRef] [PubMed]

Zhang, X.

Zhao, H.

Zhuang, X.

M. J. Rust, M. Bates, and X. Zhuang, “Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM),” Nat. Methods 3(10), 793–796 (2006).
[CrossRef] [PubMed]

Appl. Opt.

Astron. J.

L. B. Lucy, “An iterative technique for the rectification of observed distributions,” Astron. J. 79, 745–754 (1974).
[CrossRef]

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S. J. Tan, L. Yobas, G. Y. H. Lee, C. N. Ong, and C. T. Lim, “Microdevice for the isolation and enumeration of cancer cells from blood,” Biomed. Microdevices 11(4), 883 (2009).
[CrossRef] [PubMed]

Commun. Pure Appl. Math.

E. J. Candès, J. K. Romberg, and T. Tao, “Stable signal recovery from incomplete and inaccurate measurements,” Commun. Pure Appl. Math. 59(8), 1207–1223 (2006).
[CrossRef]

IEEE J. Sel. Top. Signal Processing

S.-J. Kim, K. Koh, M. Lustig, S. Boyd, and D. Gorinevsky, “An Interior-Point Method for Large-Scale l1-Regularized Least Squares,” IEEE J. Sel. Top. Signal Processing 1(4), 606–617 (2007).
[CrossRef]

IEEE Signal Process. Mag.

M. F. Duarte, M. A. Davenport, D. Takhar, J. N. Laska, K. F. Ting Sun, Kelly, and R. G. Baraniuk, “Single-pixel imaging via compressive sampling,” IEEE Signal Process. Mag. 25(2), 83–91 (2008).
[CrossRef]

J. Romberg, “Imaging via Compressive Sampling,” IEEE Signal Process. Mag. 25(2), 14–20 (2008).
[CrossRef]

IEEE Trans. Inf. Theory

E. J. Candes and T. Tao, “Near-optimal signal recovery from random projections: Universal encoding strategies?” IEEE Trans. Inf. Theory 52(12), 5406–5425 (2006).
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D. L. Donoho, “Compressed sensing,” IEEE Trans. Inf. Theory 52(4), 1289–1306 (2006).
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A. A. Adams, P. I. Okagbare, J. Feng, M. L. Hupert, D. Patterson, J. Göttert, R. L. McCarley, D. Nikitopoulos, M. C. Murphy, and S. A. Soper, “Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor,” J. Am. Chem. Soc. 130(27), 8633–8641 (2008).
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A. F. Coskun, T. W. Su, and A. Ozcan, “Wide field-of-view lens-free fluorescent imaging on a chip,” Lab Chip 10(7), 824–827 (2010).
[CrossRef] [PubMed]

S. Seo, T. W. Su, D. K. Tseng, A. Erlinger, and A. Ozcan, “Lensfree holographic imaging for on-chip cytometry and diagnostics,” Lab Chip 9(6), 777–787 (2009).
[CrossRef] [PubMed]

Langmuir

S. K. Murthy, A. Sin, R. G. Tompkins, and M. Toner, “Effect of flow and surface conditions on human lymphocyte isolation using microfluidic chambers,” Langmuir 20(26), 11649–11655 (2004).
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Magn. Reson. Med.

M. Lustig, D. Donoho, and J. M. Pauly, “Sparse MRI: The application of compressed sensing for rapid MR imaging,” Magn. Reson. Med. 58(6), 1182–1195 (2007).
[CrossRef] [PubMed]

Nat. Methods

M. J. Rust, M. Bates, and X. Zhuang, “Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM),” Nat. Methods 3(10), 793–796 (2006).
[CrossRef] [PubMed]

Nature

S. Nagrath, L. V. Sequist, S. Maheswaran, D. W. Bell, D. Irimia, L. Ulkus, M. R. Smith, E. L. Kwak, S. Digumarthy, A. Muzikansky, P. Ryan, U. J. Balis, R. G. Tompkins, D. A. Haber, and M. Toner, “Isolation of rare circulating tumour cells in cancer patients by microchip technology,” Nature 450(7173), 1235–1239 (2007).
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E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313(5793), 1642–1645 (2006).
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M. Sheikh, O. Milenkovic, and R. Baraniuk, “Designing compressive sensing DNA microarrays” IEEE Workshop on Computational Advances in Multi-Sensor Adaptive Processing (CAMSAP), St. Thomas, U.S. Virgin Islands, December (2007)

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D. Takhar, J. N. Laska, M. B. Wakin, M. F. Duarte, D. Baron, S. Sarvotham, K. F. Kelly, and R. G. Baraniuk, “A new compressive imaging camera architecture using optical-domain compression,” in Computational Imaging IV, 6065, (San Jose, CA, USA), p. 606509, SPIE, (2006).

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Figures (8)

Fig. 1
Fig. 1

(a) Schematic diagram of the lensfree on-chip fluorescent imaging platform is shown. Drawing is not to scale. This imaging platform has unit magnification such that the imaging field-of-view equals to the entire active area of the sensor array (i.e., >8 cm2). The TIR condition occurs at the glass-air interface at the bottom facet of the coverglass. To avoid detection of scattered pump photons a plastic absorption filter is used after the faceplate. Typical dimensions: w1 x w2 = 25mm x 35mm; p = 1.7 cm; k ~10-100 µm; f = 1-2 cm. (b) A microscope image of the faceplate is shown. The numerical aperture of each fiber is ~0.3.

Fig. 2
Fig. 2

(a-b) Lensfree fluorescent images of 10 µm particles are compared with and without the faceplate. To make this comparison fair, except the faceplate, all the other dimensions in Fig. 1(a) are kept the same in both of these experiments. With the use of the faceplate, the spatial spreading of the fluorescent signatures at the CCD plane is reduced from ~180 µm down to ~36 µm (FWHM). This improvement is also evident in the comparison that is provided by the digitally zoomed regions shown in (c1-f1) and (c2-f2), which correspond to experiments “without the faceplate” and “with the faceplate”, respectively. The same zoomed images of (c2-f2) are also decoded using a compressive sampling algorithm to yield (c3-f3). As further quantified in Figs. 4, 5 and 6 this compressive decoding process improves the spatial resolution down to ~10 µm all across the field of view of the sensor.

Fig. 8
Fig. 8

Same as in Fig. 7, except for 3 fluorescent layers that are vertically separated by ~100 µm from each other. Two different regions are imaged using a faceplate, and the raw lensfree images are then decoded to reveal the distribution of the fluorescent particles at each layer. In the raw lensfree images, the fluorescent signatures from the 3rd layer are rather faint and need careful examination to see them with the bare eye, whereas the decoder output for the 3rd layer faithfully resolves their location. Such a computational strength would be quite significant to further increase the throughput in e.g., imaging cytometry experiments.

Fig. 7
Fig. 7

(a) Lensfree fluorescent imaging of 2 layers that are vertically separated by ~50µm is illustrated. (b1) and (d1) show two different digitally cropped regions of the large FOV that are imaged without the use of a faceplate (see Fig. 1). The compressive decoding results of these 2 raw lensfree images for each vertical channel are illustrated in (b2-b3) and (d2-d3), respectively. The same regions are also imaged using the faceplate as shown in (c1) and (e1). The compressive decoding results of these 2 raw lensfree images for each vertical channel are also illustrated in (c2-c3) and (e2-e3), respectively.

Fig. 3
Fig. 3

(a1) shows a digitally zoomed lensfree fluorescent image of 10µm particles that is obtained without the use of a faceplate. (a2) illustrates the output of the compressive decoder for the same image in (a-1). (a3) shows the same region of interest imaged this time using a faceplate as shown in Fig. 1(a). The compressive decoder output of image (a3) is shown in (a4). The same story is repeated in (b1) through (b4) for a different region of interest. The arrows in these images specifically point to regions where the improvement due to the faceplate becomes apparent to better resolve closely spaced fluorescent particles.

Fig. 4
Fig. 4

(Top Row) shows raw lensfree fluorescent images of different pairs of 10 µm diameter particles imaged using the set-up of Fig. 1. As the particles get closer to each other, their signatures in the raw lensfree image become indistinguishable to the bare eye. The inset images in the top row (bottom right corner of each image) illustrate transmission microscope images of the same particles from which the center-to-center distance (g) in each case is calculated only for comparison purposes. (Middle Row) illustrates the results of the compressive decoding process for each lensfree image of the top row. gCS refers to the center-to-center distance of the resolved fluorescent particles in each image, where CS denotes “compressive sampling”. Even for g = 10µm case (far right column), we can clearly resolve the fluorescent particles from each other with gCS = 9µm. The pixel size in the decoded image is 3µm, whereas the raw lensfree image has been sampled with a pixel size of W = 9µm at the detector array, i.e., N = 9M . The reason that the reconstructed points for gCS = 9µm case do not touch each other (unlike the microscope image shown in the inset) is that the incoherent point-spread function of the system has been estimated using 10µm diameter fluorescent particles. Refer to Figs. 5, 6 for imaging of 2µm diameter fluorescent particles. The computation times of these decoded images vary between 0.1 min to 0.5 min on an Intel Centrino Duo Core, 1GHz PC. (Bottom Row) illustrates the deconvolution results of the Lucy-Richardson algorithm for the same set of lensfree images shown in the top row. gLR refers to the center-to-center distance of the resolved fluorescent particles in each image, where LR denotes “Lucy-Richardson”. The number of iterations [19] in these deconvolution results ranged between 200 and 400, matching with the overall computation time of the CS results for each image. These results indicate that the LR algorithm can resolve particles with g~18 µm, whereas the CS decoder can clearly resolve particles with g~10 µm.

Fig. 5
Fig. 5

Same as Fig. 4 except for 2µm diameter fluorescent particles. The raw lensfree images are decoded to resolve closely spaced particles from each other. The inset images (bottom right corner of each decoded image) illustrate regular transmission microscope images of the same particles from which the center-to-center distance (g) in each case is calculated for comparison purposes. The bottom row illustrates resolving 2µm particles that are separated by g ~12µm and 8µm. The pixel size in the raw lensfree fluorescent images is W = 9µm, whereas the pixel size of the decoded images is 2µm, i.e., N~20M . The point-spread function of the system has been estimated using 2 µm diameter fluorescent particles imaged at a low concentration.

Fig. 6
Fig. 6

Same as Fig. 5 (2µm fluorescent particles) except with a pixel size of W = 18µm at the detector-array, such that 4 pixels of the CCD are now binned together. Similar to Fig. 5, the raw lensfree images are decoded to resolve closely spaced fluorescent particles from each other. The pixel size of the decoded images is still 2µm, same as in Fig. 5, which this time implies N = 81M . Because of a significant reduction in M when compared to Fig. 5, the performance of the compressive decoding is relatively degraded, which is especially visible for reconstruction of g = 8µm case (bottom right corner). Regardless, even with N = 81M, we have achieved decoding of sub-pixel objects as shown in e.g., g = 12 µm case.

Equations (5)

Equations on this page are rendered with MathJax. Learn more.

f(x,y)=i=1Nciψi(x,y)
f(x,y)=i=1Ncip(xxi,yyi)
Im=f(x,y)ϕ(xxm,yym)dxdy
Φmp(xmxi,ymyi)ϕ(xxm,yym)dxdy=KW2p(xmxi,ymyi)
c^=argminIdetMconvc¯2+βc¯1

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