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Abstract: Rapid advancements in smartphone technology have enabled the integration of many
optical detection techniques that leverage the embedded functional components and software
platform of these sophisticated devices. Over the past few years, several research groups have
developed high-resolution smartphone-based optical spectroscopic platforms and demonstrated
their usability in different biomedical applications. Such platforms provide unprecedented
opportunity to develop point-of-care diagnostics systems, especially for resource-constrained
environments. In this review, we discuss the development of smartphone systems for optical
spectroscopy and highlight current challenges and potential solutions to improve the scope for
their future adaptability.
© 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
1. Introduction
Ever since the demonstration of the first functional mobile phone in 1973 by Martin Cooper at
Motorola [1], mobile phones have become a critical mainstay of everyday life. According to the
International Telecommunication Union (ITU), there are more than 7.8 billion active cellular
subscriptions around the globe. The high penetration of mobile phones is largely due to their
affordability and user-oriented design. Mobile phones have great potential to connect people who
are isolated from the mainstream of economic and technological development due to political
and socio-economic challenges. As a result, their widespread availability and affordability in
developing and underdeveloped countries is prompting new initiatives by many governmental or
non-governmental organizations [2].
Early versions of mobile phones were primarily intended for voice communication and mes-
saging applications. The rapid advancement in embedded technology, miniaturized electronics,
and fast computation has accelerated the evolution of mobile phone technology, ushering in the
modern-day smartphone. It is estimated that there were nearly 3.2 billion smartphone users
across the globe in 2019 [3]. The modern smartphone is not merely a communication device:
the enormous processing power, storage capacity and battery life of smartphones allows the inte-
gration of different consumer-oriented sensors (e.g., complementary metal-oxide semiconductor
(CMOS) cameras, light emitting diode (LED) flashlights, proximity and ambient light sensors
(ALS), accelerometers, global positioning system (GPS), wi-fi, graphical user interface (GUI))
with user-oriented software tools and smartphone applications (a.k.a., apps). Hence, the modern
smartphone is essentially a portable personal computer and sensing platform that lowers the
economic barriers to rapid development and deployment of scientific tools in traditional and
need-based communities [4–7].
Since the smartphone camera has become a primary selling point of these devices, continuous
efforts have been made to improve its quality over time. The modern camera phone first emerged
after the development of CMOS active pixel sensors in the early 1990s [8]. In 1999, Kyocera,
commercialized the first camera phone (VP-210) with a 0.11-megapixel (MP) front camera
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Journal © 2021 Received 10 Dec 2020; revised 25 Feb 2021; accepted 4 Mar 2021; published 10 Mar 2021
Review Vol. 12, No. 4 / 1 April 2021 / Biomedical Optics Express 1975
[9]. After this, many companies realized the potential of the smartphone’s market penetration,
and the never-ending race to increase pixel count and pixel density began. In 2000, Samsung
released their first phone with a built-in 0.35-MP camera (Samsung SCH-V200). Following
the trend, Sprint released Audiovox PM8920 in the United States with a 1.3-MP camera in
2004. In 2005, Nokia introduced their 2-MP camera phone with Carl Zeiss optics, an LED flash,
and autofocus capabilities. In 2007, Samsung released the first 5-MP camera phone, and this
resolution remained as a high-end standard for many years [10].
Smartphone cameras with higher resolution again appeared in 2010. Since the footprint of the
smartphone is small, the key strategy used to increase the pixel count is to reduce the size of pixels.
Sony released a 12-MP autofocus camera with added facilities such as face detection, geotagging
and smart contrast in 2010. Afterwards, in mid-2013, Nokia announced their smartphone, Lumia
1020, with a 41-MP camera sensor with a 1.2-µm pixel size, embedded with an f/2.4 Carl-Zeiss
all-aspherical one-group lens [11]. Due to the high resolution of the camera, this smartphone
was used to demonstrate the detection of single DNA molecules [12]. The high-pixel-count
smartphone cameras further evolved as, in 2019, Samsung developed and commercialized the
64-MP and 108-MP cameras for smartphones [13]. These densities can be found in many new
smartphones available on the market today: for example, in the Galaxy S21 from Samsung, the
Mi 10I from Xiaomi, and the Edge+ from Motorola. The 108-MP cameras process images
through pixel binning, where four or nine pixels are combined to work as a single pixel. The
use of the larger pixel enables capturing more light, which results in a higher ISO rating and
lower noise. A higher ISO rating enables detection in low-light settings, which is essential for
applications such as fluorescence-based assays [14].
Owing to the low-cost, small foot-print, low-power requirement, and vast adaptability of the
smartphone – key factors for developing affordable and point-of-care disease diagnosis platforms
– different research-based and commercial biomedical devices have been demonstrated. For
example, microscopic imaging is an important tool for the early detection and diagnosis of
many significant diseases, such as malaria. Therefore, efforts have been made by many research
groups to develop smartphone-based microscopy platforms [15–17]. Some systems simply
integrate traditional optical components [18], while others use advanced digital holographic image
processing techniques [19]. Using a simple lens and LED configuration, Zhu et al. demonstrated
the usability of the smartphone as a cost-effective imaging tool for rapid blood analysis [20].
D’Ambrosio et al. demonstrated the first video microscopy platform in a smartphone for the
detection and quantification of blood-borne filarial parasites [21].
Outside of microscopy, other implementations of smartphone-based medical devices include
examples like the CellScope Oto, a commercially available smartphone-based otoscope to
diagnose pediatric ear infections [22]. Another prominent use of the smartphone includes
point-of-care urinalysis platforms. Using a smartphone camera and machine learning approaches,
several companies and research groups have already translated laboratory-based urinalysis
to home-based detection [23,24]. Some clinical applications do not rely on the smartphone
hardware but rather leverage specially designed apps to exploit its computational platform to
process data from external medical devices. KardiaMobile is a portable electrocardiogram
(EKG) monitor that can be connected to a smartphone through wi-fi, and the EKG chart and
other heart-related information can be analyzed in the corresponding phone application [25].
Butterfly iQ is a smartphone USB-powered commercial ultrasound imaging system that brings
affordable and portable ultrasound imaging anywhere [26]. The commercial adaptation of these
smartphone-based biomedical devices opens the door to enabling other lab-confined biomedical
devices to be used as point-of-care applications.
Optical spectroscopy is a key scientific strategy to detect the presence of different biochemical
analytes based on their unique interaction with light. It has been extensively used for non-invasive
disease diagnosis and to detect numerous disease-specific biomarkers in complex sample matrices
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2.1. Camera
The optical design of the embedded camera module may vary from phone to phone. For simplicity,
it can be considered as an assembly of a focusing lens, light filters and a CMOS sensor, as shown
in Fig. 2(a). The camera module is primarily designed and intended for consumer applications
such as photography; therefore, its response is limited to the visible region. Although the sensor
chip – typically fabricated from silicon – has sensitivity in the near infrared to nearly 900 nm, the
phones usually include an infrared (IR) filter to limit the response of the camera to the wavelength
range of 400 nm to 700 nm [44]. In addition, all current-generation smartphones are embedded
with a Bayer image sensor: a pixel-sized array with red, green, and blue filters arranged in a Bayer
pattern. The inset in Fig. 2(a) shows the schematic of the Bayer pattern and the corresponding
process of digital color image formation by the CMOS sensor of the smartphone. Each pixel
Review Vol. 12, No. 4 / 1 April 2021 / Biomedical Optics Express 1977
Fig. 1. Typical position of the functional components of a smartphone used for developing
spectroscopic platforms.
records red, green, or blue light; therefore, the data from a single pixel of the image sensor
cannot fully specify a true color value on its own. A full-color image is obtained by using a
demosaicing algorithm, which interpolates a set of complete red, green, and blue values for each
super-pixel (comprising four pixels). These algorithms make use of the surrounding pixels of the
corresponding colors to estimate the values for a particular super-pixel. Each pixel contributes
a single 8-bit, grayscale intensity value (0 to 255 levels). Once reconstructed, images may be
displayed in color on the phone screen or analyzed to extract relevant information. Note that
while traditional benchtop spectroscopic systems use a 1-D photodetector array, which can detect
only one spectrum at a time, the embedded camera in a smartphone is two-dimensional and can,
therefore, be utilized to detect multiple spectra at the same time (e.g., for multiplexed detection
of biomarkers [45]).
2.2. ALS
The ALS embedded in the front panel of the smartphone is meant to optimize the consumption of
battery power. The ALS controls the brightness of the display panel automatically in accordance
with the surrounding environment. Almost all branded smartphones contain an Avago APDS-
9930 or ams AG(TAOS) TMD2771 ambient light and proximity sensor chip [46,47]. This
sensor chip has two photodiode channels: CH0 is used for light sensing and CH1 is used for
proximity sensing. As shown in Fig. 2(b), the sensor chip includes on-chip integrating amplifiers,
analog-to-digital converters (ADCs), accumulators, clocks, buffers, comparators, a state machine
and an Inter-Integrated Circuit (I2C) interface. Upon detecting light on either photodiode
channel, the amplified photodiode currents are converted to 16-bit digital values by the ADC
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unit. The converted digital values are then transferred to the CH0 and CH1 data registers of a
microprocessor for further processing. From the microprocessor, the data are sent to the central
smartphone processor through a fast, two-wire I2C serial bus. On Android phones, the ALS data
can be accessed by user-designed smartphone applications using the Android Sensor Manager
module. As shown in the posterior portion of Fig. 2(b), the responsivity for the CH0 photodiode
ranges from 350 nm to 1000 nm, while the CH1 photodiode has a responsivity range covering
450 nm to 1000 nm. The CH0 photodiode has a dynamic range of 0 Lux to 20000 Lux with a
resolution of 0.01 Lux. Due to its high dynamic range and resolution, the ALS can be an excellent
alternative to a laboratory-grade photodetector, which may find usability in many spectroscopic
applications.
LED pulse width ranges between 20 ms and 200 ms [48]. When combined with external optical
filters, the embedded LED flash can be used as a light source for many sensing applications.
way that it makes an angle of 45 degrees with a transmission grating of 1000 lines/mm, which
is essential to record the first-order diffracted wavelength spectrum by the phone camera. The
system was implemented on an iPhone 2G cellphone, which contains a 1600-pixel x 1200-pixel
CMOS sensor with a 2.2-µm pixel size. With this camera, they reported a spectral resolution of
5 nm over a 300-nm bandwidth. In order to demonstrate the potential biomedical applications
of the reported system, the transmission spectrum of 1 cm of human tissue was recorded by
inserting a finger in the path between a 60-W Tungsten bulb and the spectrometer slit. The color
bands in the middle of Fig. 4(a) show the spectrum captured by the phone from the tungsten bulb
and the finger, respectively, and the bottom figure represents the resulting transmission spectrum
generated after data processing.
Subsequently, Long et al. used a similar configuration to perform Enzyme-Linked Immunosor-
bent Assays (ELISA) at biologically relevant concentrations [50]. ELISA is one of the most
widely used biological assays for quantification of proteins and antibodies for diagnosis of
diseases ranging from cancer to HIV. The antibody-antigen interaction in an ELISA test yields
colorimetric changes to the liquid sample. The absorption of wavelengths generates a dark band
in the captured spectrum, as shown in Fig. 4(b), where the bottom portion demonstrates the
intensity plot vs. wavelength range for different dilution. The system was developed using an
iPhone 4 embedded with a 2592-pixel ⇥ 1936-pixel CMOS image sensor, which achieved a
spectral resolution of 0.334 nm/pixel with a 1200-lines/mm grating. A smartphone spectrometer
in a similar transmission configuration (Fig. 4(c)) was used by Dutta et al. to demonstrate its
usability for the detection of bioconjugation events using localized surface plasmon resonance
(LSPR) as the sensing scheme [51].
Reflection grating-based absorption spectrometers have also been demonstrated for various
biosensing applications. Wang et al. demonstrated a novel standalone smartphone sensing
platform that does not require any external light source, lens or filter [42]. In this work, the
flashlight of the smartphone was used as a light source, and a reflective compact disk (CD)
grating placed at a distance of 50 mm from the phone served as the dispersive element. As
shown in Fig. 5(a), light from the flashlight interacts with the sample solution after passing
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through a 1-mm pinhole; the modulated light gets dispersed and reflected by the CD grating,
which is then captured by the phone camera. This system was used to detect glucose utilizing
a well-known bienzymatic cascade assay. Figure 5(a) also shows the spectra captured by the
phone at different times. Since this system does not need an external light source or optics, it
reduces the overall complexity and showcases the potential of smartphone-based spectroscopic
systems to be self-contained, which is highly useful for field testing and home diagnostics.
Similarly, a reflection grating-based configuration was used by Ding et al. for the development of
a spectroscopic system for quantifying creatinine concentration with high spectral accuracy [52].
One problem with using the flashlight as a light source is that its emission spectrum is not
distributed evenly in the visible wavelength range, as can be seen from Fig. 2(c). Due to this
reason, broadband sources such as halogen lamps are used to provide a more evenly distributed
spectrum in almost all smartphone-based spectroscopic systems. These sources are difficult
to integrate into a hand-held and portable smartphone spectrometer, however, due to their size
and need for an optical fiber cable for light transmission, a driver circuit, and external power.
To mitigate this issue, Jian et al. demonstrated the use of sunlight as the illumination source,
which has a more uniform spectrum in the visible wavelength range than both the smartphone
flashlight and halogen lamps [53]. The spectrometer was designed using a smartphone with a
Review Vol. 12, No. 4 / 1 April 2021 / Biomedical Optics Express 1983
monochrome CMOS sensor (4224-pixels ⇥ 3192-pixels, 1.12-µm pixel size), which reduces the
color overlapping that occurs in traditional CMOS sensors with Bayer color filters. A resolution
of 0.276 nm/pixel was demonstrated with this system over a wavelength range of 380 nm to
760 nm. The stability of the developed platform was established using standard Rhodamine 6G
(R6G) diluted with deionized water. Figure 5(b) shows the monochrome spectrum captured
by the system and the intensity variation for different R6G concentrations. The sunlight-based
smartphone spectrometer was further used for detecting avian influenza virus (AIV) H7N9 and
porcine circovirus type 2 (PCV2) antibodies.
Many label-free biosensing methods such as surface plasmon resonance- (SPR), evanescent
wave- (EW), or photonic crystal-based (PC) biosensors are based on the intensity variation
or shift in wavelength of the transmitted light from the transducer due to the adsorption of
biomolecules [54–56]. The shift in wavelength is usually measured by a spectrometer. Gallegos et
al. demonstrated a label-free photonic crystal biosensor, where the smartphone camera was used
as the detector [57]. In this work, the PC structure was designed to behave like a high-efficiency
narrowband reflectance filter (565-nm central wavelength with 5-nm bandwidth), which allows
all wavelengths to transmit through the PC except the resonantly reflected wavelength, as shown
in Fig. 6(a). Upon adsorption of biomolecules on the PC surface, the effective refractive index
of the resonant mode increases, which results a shift in the resonantly reflected wavelength.
The magnitude of this shift is proportional to the optical density of the adsorbed molecule. A
smartphone-based spectroscopic system was developed to detect this shift in wavelength, and
its bio-detection capability was demonstrated by detecting immunoglobulin G (IgG) using an
immobilized layer of Protein A on the PC surface. The optical design is similar to that of a
smartphone-based absorption spectrometer, except the cuvette was replaced by the PC surface in
the optical path. The adjacent sub-figure in Fig. 6(a) shows the schematic and the fabricated
device. The dark band in the captured spectrum represents the wavelength band that is reflected
resonantly, and the plot shows the corresponding transmission spectrum generated by the system.
A similar configuration was used to develop an evanescent wave-coupled spectroscopic sensing
system [58]. Using a right-angled glass prism, the evanescent field generated due to total internal
reflection was allowed to interact with the external medium, which was attached to one face of
the prism. The smartphone-spectroscopic system was used to detect the shift in wavelength and
the corresponding analyte concentration.
Both the photonic crystal- and evanescent wave-based sensing systems reported above are
based on a free-space optical design. These systems require several external components to
guide the light from the external light source to the camera via the optical transducer, which
makes the overall footprint relatively bulky and costly. To reduce the overall size and cost of
such wavelength- or intensity modulation-based sensing system, Bremer et al. reported the
development of a fiber optic smartphone-based SPR sensing system. It has a very small footprint,
the required optical coupling and alignment are simple, and there is no need for external prisms
or lenses [59]. SPR sensors are based on the resonant excitation of surface plasmon waves (SPW)
or the electron density oscillations in a metal-dielectric interface caused by incident light having
a propagation constant equal to that of SPW. The associated transverse magnetic polarized waves
of the SPW are guided parallel to the metal-dielectric interface during resonance, which produces
a dip in the wavelength spectrum of the transmitted light. Since the propagation constant of the
SPW depends on the refractive index of the surrounding medium, SPR can be used for highly
sensitive biosensing applications. The SPR sensor was fabricated by coating 10 mm of the core
of an optical fiber with a thin silver layer. As shown in Fig. 6(b), the end faces of the optical fiber
were polished to 45 degrees in order to directly couple the light from the smartphone flashlight
via the SPR sensing region. The wavelength shift of the SPR due to the change in refractive index
of the sample was detected by dispersing the light into the camera using a grating. The adjacent
sub-figure in Fig. 6(b) shows the spectrum captured by the system and the shift in wavelength
Review Vol. 12, No. 4 / 1 April 2021 / Biomedical Optics Express 1984
due to variation of the refractive index. Since the SPR sensor is based on a fiber optic waveguide,
it is possible to integrate the whole system within the protective cover of the smartphone; thus,
the system can be implemented as a low-cost and disposable lab-on-a-chip system, as needed in
many biomedical applications.
the phone camera and later processed with a custom-designed phone application to generate the
reflectance spectrum. With a Samsung Galaxy smartphone (13-MP camera), a spectral resolution
as high as 2.0 nm was obtained over a bandwidth of 250 nm with a slit of width 0.7 mm.
Many paper-based assays, such as urine dipsticks, are analyzed by visual comparison against
a standard color chart. Since this method depends on the user’s color perception and the
lighting conditions, it is difficult to differentiate color variation accurately. Moreover, the colored
compound produced in the test strip usually has a complex wavelength spectrum: that is, many
wavelength components are combined to produce the final visible color. Analysis of subtle color
differences can provide accurate information and can be detected by analyzing the scattered light
by means of reflectance spectroscopy. Woodburn et al. developed a smartphone-based reflectance
spectroscopic platform for the analysis of paper-based colorimetric assays [60,61]. Similar to the
work reported by Hossein et al., in this work, white light from the smartphone’s flashlight was
coupled to an optical fiber and made incident on test strips housed in a custom-designed cartridge.
The scattered light was then collected by another optical fiber. The cartridge was designed to
manually slide over the system, and the wavelength spectrum generated by a transmission grating
was recorded as a video file. The video was processed with a custom-designed application to
obtain the characteristic wavelength spectrum from the multi-analyte test strips. The developed
system can be used for analyzing different paper-based assays to obtain accurate and precise
results, more specifically for the class of assays where conventional phone-based colorimetric
detection or analysis of the red-green-blue pixel values of a camera image is not sufficient
to measure the complex scattered spectra. A similar strategy was used by Bayram et al. in
developing a portable reflectance spectrometer for colorimetric detection of Bisphenol-A, which
is a well-known endocrine disruptive agent [62].
Diffuse reflectance spectroscopy has been extensively used for many biomedical applications
where non-invasive investigation is required. In this spectroscopic method, incident light
penetrates deeply into the tissue, gets absorbed by chromophores and is scattered by cellular
and intercellular entities. The modulated light re-emerges to the surface carrying information
about chromophore concentrations and the scattering properties of the tissue. Diffuse reflectance
spectroscopy systems are often bulky and costly due to the need for a traditional spectrometer and
heavy computational requirements. An affordable, easy-to-use and portable diffuse reflectance
spectroscopy system could significantly improve accessibility to the technology, especially in low
resource settings. Hong et al. demonstrated a dual-modality smartphone-based microendoscope
system that integrates quantitative diffuse reflectance spectroscopy and high-resolution fluores-
cence imaging for quantification of physiological and morphological properties of epithelial
tissues [63]. Figure 7(b) shows the schematic diagram of the system, which consists of a Samsung
Galaxy S6 smartphone, a 3D-printed attachment for holding optical components, a fiber-optic
microendoscope and an app for data analysis. Light from a 20-mW white LED was delivered to
the tissue through two multimode optical fibers (200-µm core diameter), and the diffusely reflected
light was collected using a single detection fiber of the same core diameter. The collected light
was then propagated through a 100-µm slit and collimated by a collimating lens. A transmission
grating (1200 lines/mm) diffracted the collimated light and then imaged it by the phone camera.
The diffuse reflectance spectrum collected by the system was wirelessly transmitted to a server
through the developed app. The data processing module in the server automatically processed the
data and sent back the results to the app for display. A spectral resolution of 2 nm was obtained
over a spectral range of 395.5 nm to 693.3 nm. The feasibility of the system in characterizing the
properties of epithelial tissue was tested in a single human subject in vivo. Spectra were recorded
from oral mucosa, including labial mucosa tissue, gingival tissue and tongue dorsum tissue,
where the ↵ and bands of oxy-hemoglobin were clearly visible, as shown in the sub-figure of
Fig. 7(b). The differences in shape and intensity of the measured spectra from the oral tissues
represent their underlying differences in physiological and morphological characteristics.
Review Vol. 12, No. 4 / 1 April 2021 / Biomedical Optics Express 1986
To make the fluorescence detection more self-contained, Hossein et al. demonstrated the
use of a smartphone battery to power external light sources in a smartphone-based fluorescent
spectroscopic system [68]. In this work, a custom gold-coated polymer grating was used as a
dispersive element, which can be fabricated inexpensively using nano-imprinting as compared to
a commercial grating. The system was designed to detect the spectrum from two analytes: a
pH-sensitive amino-phthalimide fluorescent probe and a Zn2+-sensitive fluro-ionophore. As
shown in Fig. 8(b), the excitation LEDs were powered using the phone battery and placed at an
orthogonal angle to the sample cuvette; the emitted fluorescence spectrum from the sample was
dispersed by a reflection grating and imaged by the phone camera. The captured image was then
processed by a custom-developed Android application to generate the fluorescent intensity vs.
wavelength curve within the app interface. Ding et al. further demonstrated a smartphone-based
fiber optic fluorescent spectroscopic system for mHealth applications [52]. The developed system
was used to detect creatine and urinary glucose concentration.
grating could achieve similar performance to that of the commercial grating. Similarly, Kong et
al. investigated the usability of a CD as a dispersive element in a smartphone-based spectroscopic
system and demonstrated its applicability for highly sensitive and cost-effective detection of
ascorbic acid [73]. Zhang et al. eliminated the use of a focusing lens as a spectrometer component
by using a custom-designed Fresnel lens, termed a G-Fresnel, for both focusing and dispersing
light [74]. The G-Fresnel element was fabricated by sandwiching the corresponding negative
PDMS molds of both a grating and a Fresnel lens. PDMS molds can be easily fabricated in an
affordable way through the surface-molding method. As shown in Fig. 9(b), since the G-Fresnel
element can both collimate and disperse the light, it significantly reduces the overall size of
the smartphone spectroscopic system. A spectral resolution of 1.6 nm was achieved at 595 nm,
which is more than sufficient for many biomedical applications. The usability of the system was
demonstrated by measuring protein concentrations in the well-known Bradford assay.
Fig. 9. Strategies to reduce cost and size. (a) Schematic of the smartphone spectroscopic
system developed using a DVD as a dispersive element and the SEM image of the DVD,
reproduced from Ref. [72] with permission from American Chemical Society. (b) Schematic
of the G-Fresnel element acting both as a dispersing and collimating unit and the corre-
sponding spectroscopic system developed by Zhang et al., reproduced from Ref. [74] with
permission from Royal Society of Chemistry.
Besides linear gratings, other types of gratings such as the stacked, mutually rotated diffraction
grating from SpectroClick are commercially available [75]. These gratings are manufactured in
plastic films, which makes them very affordable ($1) for enabling the development of low-cost
spectroscopic devices [76]. One way of reducing both the cost and size of spectrometers is to use
pixel-level spectral filter arrays covering wavelength bands outside of those used by the traditional
RGB Bayer color filters. In this configuration, the wavelength response at every pixel can be
calculated using a suitable demosaicing algorithm [77]. This method is most commonly used in
snapshot spectral imaging systems [78]. Since the spectral filtering is performed in the detection
layer, the overall footprint of the system would be very small, making it suitable to integrate
into a smartphone as a standalone spectral sensor. For example, Bao and Bawendi developed
a quantum-dot spectrometer in which each pixel was covered by a filter comprising a unique,
heterogeneous mixture of quantum dots with varying responsivities [79].
Linear variable filters have also been demonstrated to enable low-cost hyperspectral imaging
systems [80], where the bandpass filter is directly placed above the image sensor to capture
the corresponding wavelength spectrum. A miniaturized version of such filters could be used
Review Vol. 12, No. 4 / 1 April 2021 / Biomedical Optics Express 1991
to enable the capture of spectroscopic data by directly placing it on top of the smartphone
camera. In fact, such filters could even be used to enable responsivity outside of the traditional
spectral sensitivity of the camera if the filters themselves are capable of converting light from
one wavelength range to another. We demonstrated this general idea by using a miniature filter
composed of quantum dots to capture UV data using a smartphone [81]. Another potential way
of developing a standalone spectral sensing unit within a smartphone is to use interferometric
techniques for wavelength filtering. Custom-designed Mach-Zehnder crystal array interferometers
can be fabricated at the micro-scale using silicon photonics technology [82]. Similar to an FTIR
spectrometer, the smartphone camera could be used to capture the interferogram generated by an
interferometer array with known path differences, and the corresponding wavelength spectrum
can be generated from the interferogram using well-known Fourier transform techniques.
Fig. 10. Strategies for multiplexed operation. (a) the schematic of the multiplexed system
and the recorded spectrum developed by Wang et al., reproduced from Ref. [45] with
permission from Elsevier. (b) Microfluidics based multiplexed detection system developed
by Fan et al., reproduced from Ref. [84] with permission from MDPI.
in order of pixel count to showcase the impact of phone camera pixel resolution on the spectral
resolution. All of the systems in this table use the same dispersive element, a transmission
grating of 1200 lines/mm. It can be seen that the spectral resolution increases from 0.33 nm/pixel
for a 5-MP camera smartphone to 0.19 nm/pixel for a 20.7-MP camera smartphone. Although
the currently achieved spectral resolution is perfect for the demonstrated applications, other
biomedical applications based on different spectroscopic imaging techniques (e.g., hyperspectral
and multispectral) may require even higher spectral resolution, as the spectral resolution could
significantly impacts the overall imaging capability of the system [86]. In light of Moore’s law, we
anticipate that the quality of the CMOS sensor will improve over time with the integration of more
pixels, which can aid in increasing the spectral resolution of smartphone-based spectroscopic
systems [87]. Another way to increase the spectral resolution is to improve the integrated
optical design to cover more pixels for the target wavelength range. A higher pitch grating
can disperse the light more broadly, yielding higher resolution. If multiplexed operation is not
necessary, one may consider designing a 2D spectrometer, such as based on an echelle grating
configuration used for solar applications [88]. Besides hardware, computational algorithms such
as the high-throughput computational slit (HTCS) method can be implemented as post-processing
steps to enhance the spectral resolution [89], or one can implement other methods that combine
compressed sensing with non-linear dispersion, which have been shown to yield better spectral
resolution than could be anticipated using a traditional configuration [90].
Review Vol. 12, No. 4 / 1 April 2021 / Biomedical Optics Express 1993
Fig. 11. Smartphone spectrophotometric systems in NIR spectral range. (a) different
parts and photograph of ALS based spectrophotometric system developed by Pereira et al.,
reproduced from Ref. [28] with permission from plos.org. (b)Schematic of the photometric
system developed by Hussain et al. showing the location of embedded ALS chip in a
smartphone, reproduced from Ref. [35] with permission from IEEE. (c) Front panel of
Apple iPhone 11 smartphone.
the front panel of the Apple iPhone 11. The IR camera, flood illuminator, front camera, and dot
projector are together called a TrueDepth camera system and are used for face recognition [92].
Many other recent Android smartphones are equipped with similar face-recognition technology.
The dot projector illuminates the face with thousands of IR dots and the IR camera captures an
image of the face pattern. The IR image is then fed to a neural network to confirm its similarity
with the face pattern that was used during installation of the phone and is set to unlock the phone
if the pattern matches. Since iPhones use an encrypted platform, there is currently no publicly
available Application Programming Interface (API) to use the IR camera for functions other
than face recognition. In contrast, Android is an open-source platform, and different APIs and
applications are already available to use the IR camera to capture images [93]. The availability
of this technology will undoubtedly create new opportunities for developing IR imaging and
spectroscopic platforms for biomedical applications.
5. Conclusions
Smartphone-based systems based on different spectroscopic modalities have been successfully
introduced and applied to a vast number of biomedical applications ranging from detection of
biomolecules (protein, nucleic acids etc.) to non-invasive detection of hemoglobin from human
tissue. This review summarized the development of different smartphone-based spectroscopic
systems by highlighting the current challenges and potential solutions in achieving affordability,
portability, higher accuracy and adaptability for point-of-care applications, which are important
Review Vol. 12, No. 4 / 1 April 2021 / Biomedical Optics Express 1995
considerations for resource-constrained settings. The rapid growth of the smartphone market
paves the way for the integration of more sophisticated hardware and computational power to a
smartphone over the course of time.
In addition to the research systems described above, several portable spectrometers are available
commercially, such as the VS20-VIS from Horiba, the USB2000+ from Ocean Insight, and the
LI-180 from Licor. Their optics are distinct from components on the phone itself, but they are
able to communicate with smartphones (e.g., for data processing) using various communication
protocols (i.e., wi-fi, Bluetooth, or USB). Unfortunately, the overall cost of these spectrometers is
still high (⇠ $2000) for applications in low-resource settings. Many companies, however, have
already seized the opportunity to develop smartphone-integrated commercial spectrometers due
to their affordability. Changhong H2, a smartphone developed by Consumer Physics, Israel, has
an integrated spectrometer that can be directly used to assess the quality of medicine and food
[94]. GoSpectro is another commercially available optical attachment for the smartphone camera
designed to capture a spectrum using a phone application [95].
Besides developing the smartphone as a consumer-based product, companies like Samsung are
developing smartphones for military applications [96]. Use of smartphones on the battlefield will
open new avenues for rapid diagnostics testing such as monitoring wound infection, spectroscopic
detection of traumatic brain injury etc. The limiting factor for phone attachment-based systems is
the rapid evolution of phone designs, which change every two to three years for any phone brand. It
is envisioned that with the development of additive manufacturing techniques such as 3D printing
technology, different innovative and universal opto-mechanical designs can be created that are
suited for any phone brand. Another key limitation is the challenge of implementing high-end
machine learning (ML) or artificial intelligence (AI) algorithms in lower-end smartphones. For
these applications, data need to be processed on a remote server and then transferred back to
the smartphone for display. The ability to effectively perform this transfer depends on several
factors such as connectivity and bandwidth. The recent development of 5G technology enables
high-speed data transmission in an affordable way; therefore, it is envisioned that low-end,
5G-connected phones may be able to incorporate processing from sophisticated algorithms a
combination of using cloud-based processing and high-speed transfers. For now, widespread
adaptation of smartphone-based spectroscopic systems may seem unlikely, but we expect that
given the utility of spectroscopic analysis, this technology will eventually become ubiquitous,
similar to the adaptability of billions of smartphones currently blanketing the world.
Funding. Congressionally Directed Medical Research Programs (U0052609).
Acknowledgments. We wish to acknowledge Joseph D. Malone for his help and suggestions in preparing the
manuscript. This work was funded by the Dorothy J Wingfield Phillips Chancellor Faculty Fellowship and DOD CDMRP
U0052609.
Disclosures. The authors declare no conflicts of interest.
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