FIGURE 1 - uploaded by Xiyuan Liu
Content may be subject to copyright.
Smartphone-based microscopes for cell imaging and counting. (a) Photograph of an optofluidic fluorescence imaging cytometry developed by Zhu et al., 71 and (b) comparison of fluorescence images of microbeads taken by the mobile phone device (top) and a conventional fluorescence microscope (bottom). (c) Images of diseased blood smears taken with a smartphone microscope developed by Breslauer et al. 6 Thin smear of Giemsa-stained malaria-infected blood (top) and sickle-cell anaemia blood (bottom). White arrows point to two sickled red blood cells. Scale bars are 10 mm. (d) Schematic illustration of the Contact Scope, and (e) brightfield images of a blood smear sample acquired using the Contact Scope. 44 

Smartphone-based microscopes for cell imaging and counting. (a) Photograph of an optofluidic fluorescence imaging cytometry developed by Zhu et al., 71 and (b) comparison of fluorescence images of microbeads taken by the mobile phone device (top) and a conventional fluorescence microscope (bottom). (c) Images of diseased blood smears taken with a smartphone microscope developed by Breslauer et al. 6 Thin smear of Giemsa-stained malaria-infected blood (top) and sickle-cell anaemia blood (bottom). White arrows point to two sickled red blood cells. Scale bars are 10 mm. (d) Schematic illustration of the Contact Scope, and (e) brightfield images of a blood smear sample acquired using the Contact Scope. 44 

Source publication
Article
Full-text available
Recent advances in biomedical science and technology have played a significant role in the development of new sensors and assays for cell and biomolecular detection. Generally, these efforts are aimed at reducing the complexity and costs associated with diagnostic testing so that it can be performed outside of a laboratory or hospital setting, requ...

Contexts in source publication

Context 1
... standard microscope eyepieces and objec- tives, a smartphone-integrated microscope attachment was developed by Breslauer et al. 6 for brightfield and fluorescence imaging. Different requirements of mag- nification and resolution can be achieved by simply using different objectives. Ambient light and white LEDs are used for brightfield imaging, whereas a trans-illumination geometry incorporating a UV LED excitation source and UV filters are utilized for fluo- rescence microscopy. This device can produce high quality images of human blood cells and parasite, as well as measure their density. Thin and thick smears of P. falciparum-infected blood samples and sickle cell anemia blood samples were successfully imaged using this system. M. tuberculosis-infected sputum smear samples were also imaged, where individual tubercu- losis (TB) bacteria could be easily identified as illus- trated in Fig. 1c. Due to its ability to image, count and analyze cells in clinical samples, this platform reveals that smartphone-based microscopy can be a promising technique for disease diagnosis and water quality monitoring, particularly in remote and resource- limited ...
Context 2
... older mobile phone cameras have lower res- olutions compared to modern smartphones, a portable microscope attachment, named Contact Scope 71 and (b) comparison of fluorescence images of microbeads taken by the mobile phone device (top) and a conventional fluorescence microscope (bottom). (c) Images of diseased blood smears taken with a smartphone microscope developed by Breslauer et al. 6 Thin smear of Giemsa-stained malaria-infected blood (top) and sickle-cell anaemia blood (bottom). White arrows point to two sickled red blood cells. Scale bars are 10 mm. (d) Schematic illustration of the Contact Scope, and (e) brightfield images of a blood smear sample acquired using the Contact Scope. 44 ( Fig. 1d), 44 was developed by Navruz et al. which is capable of imaging highly dense samples using a lower resolution camera. This device employs a unique tapered fiber-optic array, where the top facet consists of fiber optic cables having a density 9-fold higher compared to the bottom facet. Samples are placed on the top facet of the array and are illuminated by LEDs. The resulting light pattern of the sample is transmitted onto the bottom facet of the array, and projected through two lenses to the phone's camera. By manu- ally rotating the fiber array with discrete angular increments (e.g., 1-2°), contact images are captured at each position and digitally fused together based on a shift-and-add algorithm through a custom-developed Android app, and displayed on the phone's screen. The Contact Scope can achieve a spatial resolution of 1.5-2.5 lm over a field of view of 1.5-15 mm. 2 Wide- field images of blood smears were obtained using the Contact Scope, which showed good agreement with images taken using a brightfield microscope. While this platform exhibits comparable imaging performance as conventional microscopy at lower magnifications, the resolution limits of this system can be further improved for imaging at higher ...

Similar publications

Article
Full-text available
Colorimetric techniques provide a useful approach for sensing application because of their low cost, use of inexpensive equipment, requirement of fewer signal transduction hardware, and, above all, their simple-to-understand results. Colorimetric sensor can be used for both qualitative analyte identification as well as quantitative analysis for man...
Article
Introduction: There is a significant interest in developing inexpensive portable biosensing platforms for various applications including disease diagnostics, environmental monitoring, food safety, and water testing at the point-of-care (POC) settings. Current diagnostic assays available in the developed world require sophisticated laboratory infras...

Citations

... Particularly prominent are lateral-flow and vertical-flow immunoassays, which have been applied to analytes ranging from pathogens, DNA amplicons, and vitamins, to host biomarkers of disease [13]. Optical readouts of these assays include established techniques such as imaging of fluorophores and light-absorbing gold and colored latex nanoparticles, as well as newer techniques such as microbubbling assay [7,[14][15][16][17][18][19][20][21][22], and our own recently introduced phosphorescent nanoparticles [23][24][25][26]. Smartphones have gradually replaced desktop scanners and emerged as suitable low-cost readers for microfluidic devices, specifically paper-based colorimetric immunoassays [27]. ...
Article
Full-text available
Rapidly growing interest in smartphone cameras as the basis of point-of-need diagnostic and bioanalytical technologies increases the importance of quantitative characterization of phone optical performance under real-world operating conditions. In the context of our development of lateral-flow immunoassays based on phosphorescent nanoparticles, we have developed a suite of tools for characterizing the temporal and spectral profiles of smartphone torch and flash emissions, and their dependence on phone power state. In this work, these tools are described and documented to make them easily available to others, and demonstrated by application to characterization of Apple iPhone 5s, iPhone 6s, iPhone 8, iPhone XR, and Samsung Note8 flash performance as a function of time and wavelength, at a variety of power settings. Flash and torch intensity and duration vary with phone state and among phone models. Flash has high variability when the battery charge is below 10%, thus, smartphone-based Point-of-Care (POC) tests should only be performed at a battery level of at least 15%. Some output variations could substantially affect the results of assays that rely on the smartphone flash.
... Basically, SPSs may be categorized into two types: i.e., (1) built-in sensors and (2) add-on sensors. As a result, this has strongly increased the fabrication of portable SPS systems for field-deployable applications [5,6]. The strong drive to utilize smartphones in sensing was due to the universal possibilities for the development of sensors based on their features: (1) contains plenty of electronics that are built-in, acoustic, and optical elements, which may be utilized as stand-alone sensors or components of sensors, (2) easy to use for adjustment allow them to be suitable in terms of integrating with peripheral electronic, acoustic, and optical modules, (3) they are handy reduced computers, (4) they provide an opportunity to add applications (apps or software), which may be established on the profitable smartphones to function the sensors, produce the signals and enable interface with consumers, (5) they are usually furnished with a global positioning system (GPS) that permits location of consumers or map the distribution of analyte in geographical regions, (6) possess wireless communication operations that may be utilized to assemble a wireless sensor network, and (7) offer userfriendly interface for consumers and finally, smartphones are uncomplicated and do not need the user to undertake any specialized training. ...
Chapter
Technological advances in smartphone have permitted a superior multiplicity for communications of devices with one other restraining human interference. A significant improvement in integration of nanosensors in smartphones for disaster management, public health emergencies, and in the aftermath of life-threatening disorderly events is needed. Since nanosensors are very sensitive towards pressure, we anticipate that the advancement of this technology will add a significant value to vulnerable countries and possibly decrease the number of deaths. Thus, in this chapter, we deliberated manners of improving the self-sufficient energy production and use in smartphones, based on current and promptly evolving technologies. Besides, enhancements in physical toughness and offline operability are also discussed. The growth of smartphone technology up to now is not equivalent, either throughout the countries or within them. Fundamentally, smartphone technology across the emerging countries is very limited, worse most of these emerging countries still experience significant number of earthquakes, leading to higher number of deaths and ultimately unending poverty and hunger.
... There have been a number of reviews on the topic (Garcia et al., 2018;Lillehoj et al., 2013;Souza Filho et al., 2014;Wang et al., 2015). Most of these retrospected the applications of smartphones in different fields (Liu et al., 2014;Morrison et al., 2018;Rateni et al., 2017). The present review, on the other hand, surveys the applications of such sensors in a more specific field, biosample analysis. ...
Article
The emergence of the smartphones has brought extensive changes to our lifestyles, from communicating with one another, to shopping and enjoyment of entertainment, and from studying to functioning at the workplace (and in the field). At the same time, this portable device has also provided new possibilities in scientific research and applications. Based on the growing awareness of good health management, researchers have coupled health monitoring to smartphone sensing technologies. Along the way, there have been developed a variety of smartphone-based optical detection platforms for analyzing biological samples, including standalone smartphone units and integrated smartphone sensing systems. In this review, we outline the applications of smartphone-based optical sensors for biosamples. These applications focus mainly on three aspects: Microscopic imaging sensing, colorimetric sensing and luminescence sensing. We also discuss briefly some limitations of the current state of smartphone-based spectroscopy and present prospects of the future applicability of smartphone sensors.
... Amongst these advancements, for example, lens-free and smartphone imaging methods bypass the restrictions of traditional optical hardware, thereby effectively overcoming either the fundamental trade-offs or the instrumentation complexity of lens-based imaging systems. These breakthroughs have exploited such versatility of adaptation and integration for cell diagnosis and analysis [15][16][17][18][19][20]. ...
Article
Full-text available
Fluorescence live-cell imaging allows for continuous interrogation of cellular behaviors, and the recent development of portable live-cell imaging platforms has rapidly transformed conventional schemes with high adaptability, cost-effective functionalities and easy accessibility to cell-based assays. However, broader applications remain restrictive due to compatibility with conventional cell culture workflow and biochemical sensors, accessibility to up-right physiological imaging, or parallelization of data acquisition. Here, we introduce miniaturized modular-array fluorescence microscopy (MAM) for compact live-cell imaging in flexible formats. We advance the current miniscopy technology to devise an up-right modular architecture, each combining a gradient-index (GRIN) objective and individually-addressed illumination and acquisition components. Parallelization of an array of such modular devices allows for multi-site data acquisition in situ using conventional off-the-shelf cell chambers. Compared with existing methods, the device offers a high fluorescence sensitivity and efficiency, exquisite spatiotemporal resolution (∼3 µm and up to 60 Hz), a configuration compatible with conventional cell culture assays and physiological imaging, and an effective parallelization of data acquisition. The system has been demonstrated using various calibration and biological samples and experimental conditions, representing a promising solution to time-lapse in situ single-cell imaging and analysis. © 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
... Third-party tools paired with smartphone cameras are versatile diagnostic instruments [54]. Visual analysis of paper-based immunoassays replace expensive laboratory equipment [55] for detection of osteoarthritis biomarkers [56], quantifying pH levels in sweat and saliva for dehydration monitoring [57], detecting of antibodies in blood plasma using bioluminescence [58], detection of cancerous cells using light diffraction [59], and quantifying salmonella from paper microfluidics [60]. ...
... They observe external biomarkers using sensors such as a camera [11], [41], microphone [13], accelerometer [42], and WiFi [76]. Invasive measurements are achieved by pairing invasive techniques, such as drawing blood, with a separate second stage of sensing such as combining a smartphone's camera with a modality transformation mechanism such as a colorimetric strip [55], [77]. ...
... Signal interference deals with situations where sensors are ineffective and involves purposefully altering the target system through addition, subtraction, or manipulation [55], [79] (Ṁ, , ). An unaltered smartphone camera is not sufficient to quantify pathogens in a blood sample due to the size of the cells. ...
Article
Full-text available
Information within systems can be extracted through side-channels; unintended communication channels that leak information. The concept of side-channel sensing is explored, in which sensor data is analysed in non-trivial ways to recover subtle, hidden or unexpected information. Practical examples of side-channel sensing are well known in domains such as cybersecurity (CYB), but are not formally recognised within the domain of medical diagnostics and monitoring (MDM). This article reviews side-channel usage within CYB and MDM, identifying techniques and methodologies applicable to both domains. We establish a systematic structure for the use of side-channel sensing in MDM that is comparable to existing structures in CYB, and promote cross-domain transferability of knowledge, mindsets, and techniques.
... [3][4][5][6] The use of these microscopes in ophthalmology is largely restricted to the laboratory which is costly, time-consuming, and labor-intensive. [7] There is growing interest to develop tools for health monitoring which can be used in a clinical setting and fields/camp setups. [8][9][10] Point-of-care (POC) diagnostics are being developed by researchers to offer advantages over the conventional laboratory-based evaluation methods, providing portability, automation, faster processing time reduced sample volume and lower cost. ...
Article
Microscopes play an important role in the diagnosis of microorganisms and pathological lesions in ophthalmology guiding us to the appropriate management. The current trend of collecting samples and examination is mostly laboratory-based which consume time, labor, and are costly. Smartphones are being used in different fields of ophthalmology with great ubiquity. The good quality photographs obtained by smartphones along with the ease of mobility has made it possible to warrant its use in the microscopic world. This article describes a simple novel technique of preparing an intraocular lens system which can be used in conjunction with a smartphone to detect microorganisms and pathological lesions.
... Several smartphone-based diagnostic platforms have been developed by assembling all of these elements (LEDs, additional lenses, and necessary filters) into standalone attachments for a smartphone [44][45][46] . These attachments are traditionally tailored to the specific hardware of the smartphone model that they are attached to; however, due to the ever-changing technology of mobile phones, an attachment whose design is independent from a specific phone model is preferred. ...
Article
Full-text available
Fluorescence microscopy: Smartphone solutions for seeing cells A method of turning a smartphone into a fluorescence microscope, developed by researchers in the US and China, enables complex biomedical analyses to be performed rapidly and inexpensively. Conventional fluorescence microscopes are vital for detecting specific cell types and proteins, but are bulky and inconvenient for point-of-care diagnoses. Tony Jun Huang at Duke University, Dawei Zhang at USST and co-workers used liquid polymers to create miniature lenses comprising two droplets, one inside the other, dyed with colored solvents. The lenses, which are compatible with several different smartphone cameras, allowed the researchers not only to observe and count cells, but also to monitor the expression of fluorescently-tagged genes, and to distinguish between normal tissue and tumors. This ingenious use of easily-accessible and affordable smartphone technology will lead to better on-site personalized medicine, especially for developing countries.
... Various rRNA genes are separated by some non-transcribed compartments. Combined with fluorescent labeling, smartphones can help to detect microbes and parasites, even subcellular proteins and nucleic acids in vitro [112][113][114]. Agarwal et al. recently reported the use of smartphonebased digital imaging in the diagnosis of fungal keratitis and follow-up surveys [115]. ...
... There are more than 2 billion smartphone users in the world [18]. Since modern smartphones are not only portable and connected to the communication network but are also equipped with a lightweight, high-performance camera/imaging module, they have become the preferred tool for use in many POC applications [10,11,19,20]. In the clinical perspective, the smartphone-camera-based devices are being widely tested for various diagnostic applications [21][22][23][24], and the well-known examples include portable spectrophotometers, fluorescence analyzers, and microscopes [25]. ...
Article
Full-text available
Accurate and rapid diagnosis of highly pathogenic avian influenza A H5N1 is of critical importance for the effective clinical management of patients. Here, we developed a rapid and simultaneous detection toolkit for influenza A H5 subtype viruses in human samples based on a bioconjugate of quantum dots (QDs) assembly and a smartphone-based rapid dual fluorescent diagnostic system (SRDFDS). Methods: Two types of QDs were assembled on a latex bead to enhance the detection sensitivity and specificity of influenza A infection (QD580) and H5 subtype (QD650). The dual signals of influenza A and H5 subtype of H5N1-infected patients were detected simultaneously and quantified separately by SRDFDS equipped with two emission filters. Results: Our results showed a high sensitivity of 92.86% (13/14) and 78.57% (11/14), and a specificity of 100% (38/38, P < 0.0001) and 97.37% (37/38) for influenza A and H5 subtype detection, respectively. Conclusion: Therefore, our multiplex QD bioconjugates and SRDFDS-based influenza virus detection toolkit potentially provide accurate and meaningful diagnosis information with improved detection accuracies and sensitivities for H5N1 patients.
... Examples include optical and fluorescence imaging [20], microtiter assay interpretation [21], immunologic detection (e.g. microfluidic chips [22][23][24]; antibody-conjugated strips [25]) and nucleic acid detection (e.g., microfuge tubes [26,27]; microtiter plates [28]; microfluidic chambers [29]; microfluidic chips [30][31][32][33][34][35][36]). Although these are notable advances in terms of broadening access to sophisticated molecular diagnostics, translation to clinical utility using patient-derived samples has been limited (e.g., HIV blood samples [24], influenza throat swabs [25], Chlamydia trachomatis swabs [36]). ...
Article
Full-text available
Background: There is an urgent need for rapid, sensitive, and affordable diagnostics for microbial infections at the point-of-care. Although a number of innovative systems have been reported that transform mobile phones into potential diagnostic tools, the translational challenge to clinical diagnostics remains a significant hurdle to overcome. Methods: A smartphone-based real-time loop-mediated isothermal amplification (smaRT-LAMP) system was developed for pathogen ID in urinary sepsis patients. The free, custom-built mobile phone app allows the phone to serve as a stand-alone device for quantitative diagnostics, allowing the determination of genome copy-number of bacterial pathogens in real time. Findings: A head-to-head comparative bacterial analysis of urine from sepsis patients revealed that the performance of smaRT-LAMP matched that of clinical diagnostics at the admitting hospital in a fraction of the time (~1 h vs. 18-28 h). Among patients with bacteremic complications of their urinary sepsis, pathogen ID from the urine matched that from the blood - potentially allowing pathogen diagnosis shortly after hospital admission. Additionally, smaRT-LAMP did not exhibit false positives in sepsis patients with clinically negative urine cultures. Interpretation: The smaRT-LAMP system is effective against diverse Gram-negative and -positive pathogens and biological specimens, costs less than $100 US to fabricate (in addition to the smartphone), and is configurable for the simultaneous detection of multiple pathogens. SmaRT-LAMP thus offers the potential to deliver rapid diagnosis and treatment of urinary tract infections and urinary sepsis with a simple test that can be performed at low cost at the point-of-care. FUND: National Institutes of Health, Chan-Zuckerberg Biohub, Bill and Melinda Gates Foundation.