Biomedical Engineering Reference
In-Depth Information
significant cost or complexity to our field-portable tomographic microscopes, which
is an important advantage compared to laser-based holographic imaging approaches.
Another important advantage of holographic recording with unit fringe mag-
nification is the elimination of highly coherent illumination sources (e.g., lasers),
which significantly reduces various noise terms such as speckle and multiple inter-
ference noise. That is, the partially coherent illumination acquires sufficient spatial
coherence as it propagates 40-100 mm after the pinhole toward the sensor chip,
which permits holographic recording of the interference between the background
light (reference wave) and the scattered light (object wave). Moreover, owing to the
quasi-planar reference wave and the short sample-to-sensor distance, the optical
path difference between the reference and object waves is typically within the
temporal coherence length range of the illumination that has
1-15 nm spectral
bandwidth. This reduced coherence requirement at the source end permits the use
of a large pinhole (e.g., 0.05-0.1 mm diameter), thereby removing the need for any
coupling optics (e.g., an objective lens mounted on a mechanical stage) between
the light source and the pinhole. As shown in [ 10 ], in partially coherent digital
in-line holography, the demagnified image of the pinhole at the detector plane is
effectively convolved with the recorded optical field. Nevertheless, this does not
pose any limitation in our imaging geometry due to the large z 1 =z 2 ratio, giving rise
to a demagnification factor of
100-200, which effectively scales the pinhole size
down to <1m at the detector plane.
An important limitation of lensfree on-chip holography, which is common to
all in-line transmission holography schemes, is that it requires the samples to have
relatively low optical density. Since a separate reference wave is not generated
in an in-line imaging geometry, dense samples lead to excessive distortion of the
reference wave, and the detected intensity at the sensor chip becomes dominated
by the non-holographic self-interference terms (i.e., the second term in Eq. 4.1
of Sect. 4.2 ). As a result, our lensfree telemedicine microscopes, which work
in transmission geometry, cannot image dense samples such as histopathology
slides. This task, however, can be achieved by alternative reflection-based lensfree
holography approaches, which are not discussed in this chapter.
In addition to sharing the common requirements of in-line holographic imaging,
especially regarding the relatively lower spatial density of the samples, lensfree
tomographic microscopes additionally require the objects to satisfy the so-called
projection approximation [ 22 , 49 , 59 ]. This approximation necessitates that the
digitally reconstructed images represent a line integral of a property of interest
of the object (scattering, absorption, phase, etc.). This requires that each spatially
connected object should be a relatively weak scatterer such that it is not thicker than
the depth of field of the reconstructed images.
In conclusion, lensfree on-chip holography is a promising computational
microscopy platform offering high-throughput imaging of biochips within a
compact, cost-effective, lightweight, and mechanically robust architecture. These
devices can provide a new toolset for point-of-care diagnostics and telemedicine
applications by facilitating important tasks such as microscopic analysis, cytometry,
and detection of infectious diseases.
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