Label-free cellphone microscopy with submicron resolution through high-index contact ball lens for in vivo melanoma diagnostics and other applications

Jin, Boya; Bidney, Grant W.; Anisimov, Igor; Limberopoulos, Nicholaos I.; Allen, Kenneth W.; Maslov, A. V.; Astratov, Vasily N.

doi:10.1117/12.2609911

Cited by 3 publications

(6 citation statements)

References 17 publications

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“…An integration of millimeter‐scale ball lenses with index close to two with a smartphone allows the developing pocket‐size microscopes that can be used for biopsy‐free diagnostics of skin diseases. In contrast to previous studies, the compound ball lens/cellphone camera objective has the best resolution ≈0.67 µm at λ = 589 nm [ 646, 647, 658, 659 ] that corresponds to diffraction‐limited imaging with NA ≈ 0.4. Further increase of the resolution might become possible under two conditions: a) use of microspheres with diameters from several microns up to several tenths microns instead of millimeter‐scale ball lenses, b) use of short‐period nanoplasmonic arrays creating a “hot spot” plasmonic illumination for nanoscale objects.…”

Section: Discussionmentioning

confidence: 83%

“…A combination of smartphone microscopy with MSI methods allowed to suggest a radical way [ 646, 647, 658, 659 ] to dramatically increase the magnification and to exceed the resolution limitation determined by the pixilation of the cellphone sensor array. In the limit of geometrical optics, the lateral image magnification ( M ) of ball lens is determined by the following equation [ 656 ] :

\begin{equation}M\ \left( {n^{\prime},D,g} \right) = \frac{{ - n^{\prime}}}{{2\left( {n^{\prime} - 1} \right)\left( {\frac{{2g}}{D} + 1} \right) - n^{\prime}}} \end{equation}

where D is the diameter of the ball lens,

n^{\prime} = {{{{n}_{sp}}} {/ {\vphantom {{{n}_{sp}} {{n}_0}}}}{{{n}_0}}}

is the refractive index contrast between the spherical ball lens and object space, and g is the gap between the object and ball lens.…”

Section: Smartphone Ball Lens Microscopymentioning

confidence: 99%

“…One example is interferometric techniques [145][146][147] discussed in Topic 28. Another example is the integration of micro-spheres or millimeter-scale ball lenses [646,647] with cellphone imaging that permits building pocket-size microscopes as discussed in Topic 26.…”

Section: Integration With Other Super-resolution Techniquesmentioning

confidence: 99%

“…Recently, it was shown that significantly larger millimeter-scale ball lenses with refractive index close to two provide large image magnifications (M>30) in contact conditions with the samples that allows to overcome the resolution limitations coming from the pixilation of the cellphone sensor array and achieve truly diffractionlimited resolution ≈0.7 μm for visible light. [646,647,658,659] It allows developing pocket-size handheld microscopes with the diffraction-limited resolution for a variety of applications.…”

Section: Statusmentioning

confidence: 99%

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Roadmap on Label‐Free Super‐Resolution Imaging

Astratov,

Sahel,

Eldar

et al. 2023

Laser & Photonics Reviews

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Label‐free super‐resolution (LFSR) imaging relies on light‐scattering processes in nanoscale objects without a need for fluorescent (FL) staining required in super‐resolved FL microscopy. The objectives of this Roadmap are to present a comprehensive vision of the developments, the state‐of‐the‐art in this field, and to discuss the resolution boundaries and hurdles that need to be overcome to break the classical diffraction limit of the label‐free imaging. The scope of this Roadmap spans from the advanced interference detection techniques, where the diffraction‐limited lateral resolution is combined with unsurpassed axial and temporal resolution, to techniques with true lateral super‐resolution capability that are based on understanding resolution as an information science problem, on using novel structured illumination, near‐field scanning, and nonlinear optics approaches, and on designing superlenses based on nanoplasmonics, metamaterials, transformation optics, and microsphere‐assisted approaches. To this end, this Roadmap brings under the same umbrella researchers from the physics and biomedical optics communities in which such studies have often been developing separately. The ultimate intent of this paper is to create a vision for the current and future developments of LFSR imaging based on its physical mechanisms and to create a great opening for the series of articles in this field.

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Section: Discussionmentioning

confidence: 83%

\begin{equation}M\ \left( {n^{\prime},D,g} \right) = \frac{{ - n^{\prime}}}{{2\left( {n^{\prime} - 1} \right)\left( {\frac{{2g}}{D} + 1} \right) - n^{\prime}}} \end{equation}

where D is the diameter of the ball lens,

n^{\prime} = {{{{n}_{sp}}} {/ {\vphantom {{{n}_{sp}} {{n}_0}}}}{{{n}_0}}}

is the refractive index contrast between the spherical ball lens and object space, and g is the gap between the object and ball lens.…”

Section: Smartphone Ball Lens Microscopymentioning

confidence: 99%

Section: Integration With Other Super-resolution Techniquesmentioning

confidence: 99%

Section: Statusmentioning

confidence: 99%

See 2 more Smart Citations

Roadmap on Label‐Free Super‐Resolution Imaging

Astratov,

Sahel,

Eldar

et al. 2023

Laser & Photonics Reviews

View full text Add to dashboard Cite

show abstract

“…[25] Successes and limitations of MSI microscopy led to a proposal to use high-index ball lenses with significantly larger diameters spanning the range from meso-to millimeter-scale in similar applications, especially in the context of developing high-resolution cellphone-based microscopes. [52][53][54] The ball lenses with n ≈ 2 represent a case of special interest since, according to the paraxial ray tracing, they focus light exactly, on the shadow-side surface of such lenses [55] and, hence, a supermagnified contact-ball imaging is expected.…”

Section: Introductionmentioning

confidence: 99%

Ball Lens‐Assisted Cellphone Imaging with Submicron Resolution

Jin

Jean

Maslov³

et al. 2023

Laser & Photonics Reviews

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One of the most significant developments in life sciences—the discovery of bacteria and protists—was accomplished by Antoni van Leeuwenhoek in the 17th century using a single ball lens microscope. It is shown that the full potential of single lens designs can be realized in a contact mode of imaging by ball lenses with a refractive index of n ≈ 2, suitable for developing compact cellphone‐based microscopes. The quality of imaging is comparable to basic compound microscopes, but with a narrower field‐of‐view, and is demonstrated for various biomedical samples. The maximal magnification (M > 50) with the highest resolution (≈0.66 µm at λ = 589 nm) is achieved for imaging of nanoplasmonic structures by ball lenses made from LASFN35 glass, the index of which is tuned near n = 2 using chromatic dispersion. Due to limitations of geometrical optics, the imaging theory is developed based on an exact numerical solution of the Maxwell equations, including spherical aberration and the nearfield coupling of a point source. The modeling is performed using multiscale analysis: from the field propagation inside ball lenses with diameters 30 < D/λ < 4000 to the formation of the diffracted field at distances of ≈105 λ. It is shown that such imaging enables the transition from pixel‐ to diffraction‐limited resolution in cellphone microscopy.

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Sub-50 nm optical imaging in ambient air with 10× objective lens enabled by hyper-hemi-microsphere

Zhou

Hong

2023

Light Sci Appl

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Optical microsphere nanoscope has great potential in the inspection of integrated circuit chips for semiconductor industry and morphological characterization in biology due to its superior resolving power and label-free characteristics. However, its resolution in ambient air is restricted by the magnification and numerical aperture (NA) of microsphere. High magnification objective lens is required to be coupled with microsphere for nano-imaging beyond the diffraction limit. To overcome these challenges, in this work, high refractive index hyper-hemi-microspheres with tunable magnification up to 10× are proposed and realized by accurately tailoring their thickness with focused ion beam (FIB) milling. The effective refractive index is put forward to guide the design of hyper-hemi-microspheres. Experiments demonstrate that the imaging resolution and contrast of a hyper-hemi-microsphere with a higher magnification and larger NA excel those of a microsphere in air. Besides, the hyper-hemi-microsphere could resolve ~50 nm feature with higher image fidelity and contrast compared with liquid immersed high refractive index microspheres. With a hyper-hemi-microsphere composed microscale compound lens configuration, sub-50 nm optical imaging in ambient air is realized by only coupling with a 10× objective lens (NA = 0.3), which enhances a conventional microscope imaging power about an order of magnitude.

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Label-free cellphone microscopy with submicron resolution through high-index contact ball lens for in vivo melanoma diagnostics and other applications

Cited by 3 publications

References 17 publications

Roadmap on Label‐Free Super‐Resolution Imaging

Roadmap on Label‐Free Super‐Resolution Imaging

Ball Lens‐Assisted Cellphone Imaging with Submicron Resolution

Sub-50 nm optical imaging in ambient air with 10× objective lens enabled by hyper-hemi-microsphere

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