High-Throughput Lens-Free Blood Analysis on a Chip

Seo, Sungkyu; Isikman, Serhan O.; Şencan, İkbal; Mudanyali, Onur; Su, Ting‐Wei; Bishara, Waheb; Erlinger, Anthony

doi:10.1021/ac1007915

Cited by 130 publications

(103 citation statements)

References 19 publications

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“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] Among these approaches, lensfree digital holography deserves a special attention since with new computational algorithms and mathematical models, [21] it has the potential to make the most out of this digital revolution.…”

Section: Summary Of Our Achievements On Lensfree Holographic Imaging mentioning

confidence: 99%

Lensless Imaging for Battlefield On-Chip Blood Diagnostics

Özcan¹

2010

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The public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. In this proposal timeline (1 Year total) we developed a new lensless on-chip imaging platform, termed LUCAS, to enable both diagnostic and sensing capabilities within a cost-effective hand-held unit that is specifically suitable for the battlefield settings. We established the proof of concepts of this imaging modality to achieve reliable and repeatable quantified whole blood analysis and compared our results against commercially available blood analyzers. Furthermore, we investigated the fundamental limits on the size of the detectable cell/bacteria with this ABSTRACTIn this proposal timeline (1 Year total) we developed a new lensless on-chip imaging platform, termed LUCAS, to enable both diagnostic and sensing capabilities within a cost-effective hand-held unit that is specifically suitable for the battlefield settings. We established the proof of concepts of this imaging modality to achieve reliable and repeatable quantified whole blood analysis and compared our results against commercially available blood analyzers. Furthermore, we investigated the fundamental limits on the size of the detectable cell/bacteria with this platform. These accomplishments resulted in several refereed journal and conference articles. This research effort included one postdoctoral scholar as well as one graduate student working under the leadership of the PI.

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Section: Summary Of Our Achievements On Lensfree Holographic Imaging mentioning

confidence: 99%

Lensless Imaging for Battlefield On-Chip Blood Diagnostics

Özcan¹

2010

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“…S1, due to the inherently long depth-of-focus of digital in-line holography (32, 33). Accordingly, despite the fact that holographic reconstruction can be numerically focused at different depths, sectioning of planes closer than approximately 50 μm has not been feasible with lens-free wide-field holographic microscopes regardless of their detection numerical apertures (25)(26)(27)(28)(29)(30)(31). In this manuscript, this fundamental limitation will be addressed through multiangle lensfree holographic microscopy that lends itself to tomographic imaging of the samples within a large volume on a chip.…”

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“…Along the same lines, we have recently developed an alternative lens-free imaging platform that combines high resolution and large FOV in a compact, on-chip imaging architecture (25)(26)(27)(28)(29). In this modality, digital in-line holograms of micro-objects are recorded on a sensor array using partially coherent illumination with unit fringe magnification such that the entire active area of the sensor serves as the imaging FOV.…”

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“…In order to provide complementary solutions to these aforementioned needs, several lens-free digital microscopy techniques (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) were introduced over the last few years. Along the same lines, we have recently developed an alternative lens-free imaging platform that combines high resolution and large FOV in a compact, on-chip imaging architecture (25)(26)(27)(28)(29).…”

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Lens-free optical tomographic microscope with a large imaging volume on a chip

Isikman

Bishara²,

Mavandadi³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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203

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We present a lens-free optical tomographic microscope, which enables imaging a large volume of approximately 15 mm 3 on a chip, with a spatial resolution of <1 μm× < 1 μm× < 3 μm in x, y and z dimensions, respectively. In this lens-free tomography modality, the sample is placed directly on a digital sensor array with, e.g., ≤4 mm distance to its active area. A partially coherent light source placed approximately 70 mm away from the sensor is employed to record lens-free in-line holograms of the sample from different viewing angles. At each illumination angle, multiple subpixel shifted holograms are also recorded, which are digitally processed using a pixel superresolution technique to create a single high-resolution hologram of each angular projection of the object. These superresolved holograms are digitally reconstructed for an angular range of AE50°, which are then back-projected to compute tomograms of the sample. In order to minimize the artifacts due to limited angular range of tilted illumination, a dual-axis tomography scheme is adopted, where the light source is rotated along two orthogonal axes. Tomographic imaging performance is quantified using microbeads of different dimensions, as well as by imaging wild-type Caenorhabditis elegans. Probing a large volume with a decent 3D spatial resolution, this lens-free optical tomography platform on a chip could provide a powerful tool for high-throughput imaging applications in, e.g., cell and developmental biology. L ight microscopy has been an irreplaceable tool in life sciences for several centuries. The quest to resolve smaller features with better resolution and contrast has improved the capabilities of this important tool at the cost of relatively increasing its size and complexity (1). On the other hand, we have experienced the flourishing of emerging technologies such as microfluidic and lab-on-a-chip systems, which offer fast and efficient handling and processing of biological samples within highly miniaturized architectures (2-7). The optical inspection of the specimen, however, is still being performed by conventional light microscopes, which has in general several orders of magnitude size mismatch compared to the scale of the microfluidic systems. As a result, there is a clear need for alternative compact microscopy modalities toward integration with miniaturized lab-on-a-chip platforms (8).The push for new optical microscopy modalities is not solely driven by the need for miniaturization and microfluidic integration. The fact that high resolution is achieved at the cost of significant field-of-view (FOV) reduction is another fundamental limitation of lens-based imaging. The relatively small FOV of conventional light microscopy brings additional challenges for its application to several important problems such as rare cell imaging or optical phenotyping of model organisms (9-15), where high-throughput microscopy is highly desired.In order to provide complementary solutions to these aforementioned needs, several lens-free digital microscopy techniqu...

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“…As long as this spatial coherence diameter at the sample plane is larger than the diffraction size of each sample at the sensor plane, the scattered light from each object can faithfully interfere with the background light, creating a lensfree in-line hologram of the sample. These acquired lensfree holograms can then be rapidly processed using iterative phase recovery approaches to reconstruct a transmission bright-field image of the sample volume [5][6][7] . For this holographic illumination end, a longer wavelength LED (i.e., 625-700 nm) is selected since the absorption filters that are used to block the excitation light are high-pass filters with typical cut-off wavelengths of e.g., 500-600nm, which permits acquisition of transmission in-line holograms of the samples without an issue.…”

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Lensless Fluorescent Microscopy on a Chip

Coşkun

Şencan

et al. 2011

JoVE

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On-chip lensless imaging in general aims to replace bulky lens-based optical microscopes with simpler and more compact designs, especially for high-throughput screening applications. This emerging technology platform has the potential to eliminate the need for bulky and/or costly optical components through the help of novel theories and digital reconstruction algorithms. Along the same lines, here we demonstrate an on-chip fluorescent microscopy modality that can achieve e.g., <4μm spatial resolution over an ultra-wide field-of-view (FOV) of >0.6-8 cm 2 without the use of any lenses, mechanical-scanning or thin-film based interference filters. In this technique, fluorescent excitation is achieved through a prism or hemispherical-glass interface illuminated by an incoherent source. After interacting with the entire object volume, this excitation light is rejected by total-internal-reflection (TIR) process that is occurring at the bottom of the sample micro-fluidic chip. The fluorescent emission from the excited objects is then collected by a fiber-optic faceplate or a taper and is delivered to an optoelectronic sensor array such as a charge-coupled-device (CCD). By using a compressive-sampling based decoding algorithm, the acquired lensfree raw fluorescent images of the sample can be rapidly processed to yield e.g., <4μm resolution over an FOV of >0.6-8 cm 2 . Moreover, vertically stacked micro-channels that are separated by e.g., 50-100 μm can also be successfully imaged using the same lensfree on-chip microscopy platform, which further increases the overall throughput of this modality. This compact on-chip fluorescent imaging platform, with a rapid compressive decoder behind it, could be rather valuable for high-throughput cytometry, rare-cell research and microarray-analysis. Video LinkThe video component of this article can be found at http://www.jove.com/details.php?id=3181 ProtocolIn this section, we will review the experimental methods of our lensless on-chip fluorescent microscopy platform [1][2][3][4] . To demonstrate the capabilities of this technique, we will show on-chip imaging results for fluorescent micro-particles and labeled white blood cells. Although not discussed here, the same lensfree fluorescent microscopy platform can also be used to image small model animals such as transgenic C. elegans samples 3 .

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High-Throughput Lens-Free Blood Analysis on a Chip

Cited by 130 publications

References 19 publications

Lensless Imaging for Battlefield On-Chip Blood Diagnostics

Lensless Imaging for Battlefield On-Chip Blood Diagnostics

Lens-free optical tomographic microscope with a large imaging volume on a chip

Lensless Fluorescent Microscopy on a Chip

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