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DE GRUYTER Current Directions in Biomedical Engineering 2020;6(3): 20203134 Dorina Hasselbeck*, Max B. Schäfer, Kent W. Stewart, Peter P. Pott Diagnostic Capabilities of a Smartphone- Based Low-Cost Microscope Abstract: Microscopy enables fast and effective diagnostics. has to be sufficient to enable a wide range of diagnostic However, in resource-limited regions microscopy is not applications. accessible to everyone. Smartphone-based low-cost Several smartphone-based microscopes have already been microscopes could be a powerful tool for diagnostic and developed [2, 3]. The approach of Switz et al.  is based on educational purposes. In this paper, the imaging quality of a an additional inverted smartphone camera lens in front of the smartphone-based microscope with four different optical smartphone (see Fig. 1a). This type of optical system allows parameters is presented and a systematic overview of the cost-effective microscopy with a relatively high resolution and resulting diagnostic applications is given. With the chosen a large field of view (FOV). Consisting out of two lenses, the configuration, aiming for a reasonable trade-off, an average magnification of this setup can be calculated by Eq. 1, shown resolution of 1.23 µm and a field of view of 1.12 mm was in Fig. 1. Since the focal length of both lenses is in the same achieved. This enables a wide range of diagnostic applications order of magnitude, there is no or only limited optical such as the diagnosis of Malaria and other parasitic diseases. magnification. However, since the sensor of a smartphone has a higher number of pixels than its screen, the image can be Keywords: Smartphone-based Microscope, Diagnostics, digitally magnified if full resolution information is needed. Malaria, Parasites, Neglected Tropical Diseases (NTDs) Inverted Smartphone Smartphone https://doi.org/10.1515/cdbme-2020-3134 Camera Lens Camera Object (1) 𝑀 = − 1 Introduction 𝑓 𝑓 a b Microscopy is an important tool for science and medicine. As Figure 1: (a) Optical principle of the smartphone-based a diagnostic method, it is considered the gold standard for microscope; (b) Eq. (1) to calculate the optical magnification. numerous diseases. However, in many resource-limited regions, microscopy equipment is not available. Smartphone- In this work, a smartphone-based low-cost microscope with an based low-cost microscopes have the potential to enable inverted smartphone camera lens and a monolithic focusing microscopy diagnostics in these regions. Currently, mechanism is used . It is crucial that the smartphone-based smartphones are very abundant and there will be an estimated microscope achieves a high resolution to enable a wide range number of 6.4 billion smartphones in the world by 2021 . of diagnostic applications. Various studies showed that the Additionally, the integrated smartphone camera systems have diagnosis of some diseases is already possible [5, 6]. In this improved significantly in recent years, resulting in the work, the highest possible resolution without changing the possibility of developing high-resolution smartphone-based requirements of the used smartphone was determined and a microscopes with an advanced but low-cost optical system. To systematic overview of the diagnostic applications of the be an adequate replacement for conventional laboratory smartphone-based microscope is provided. microscopes the resolution of a smartphone-based microscope 2 Materials and Methods ______ *Corresponding author: Dorina Hasselbeck: Institute of 2.1 Optical System Medical Device Technology, Pfaffenwaldring 9, University of Stuttgart, Germany, e-mail: email@example.com A smartphone-based microscope developed previously , is Max B. Schäfer, Kent W. Stewart, Peter P. Pott: Institute of used to determine the potential applications. To evaluate what Medical Device Technology, University of Stuttgart, Germany Open Access. © 2020 Dorina Hasselbeck et al., published by De Gruyter. This work is licensed under the Creative Commons Attribution 4.0 License. Dorina Hasselbeck et al., Diagnostic Capabilities of a Smartphone-Based Low-Cost Microscope — 2 resolution is achievable, four different lenses, taken from target size, the FOV was determined by referring to the pixel smartphone camera modules, are tested in the smartphone- size of the respective smartphone. based microscope frame (Fig. 2a). The lenses were taken from smartphone models from Apple (Apple Inc., Cupertino, CA, 2.3 Diagnostic Applications US) and Samsung (Samsung Electronics Co. Ltd., Suwon, KR) (see Table 1). Four different lenses with different focal A literature research was performed focusing on diseases that lengths, 𝑓′ , were tested to verify if a shorter focal objective lens can be diagnosed by conventional light microscopy. This length results in a higher optical magnification and therefore investigation provided information about the potential in a higher resolution. diagnostic applications of the smartphone-based microscope. The structural sizes of the pathogens or physiological Table 1: Used smartphone camera lenses and their properties. structures were determined in order to compare to the Smartphone Module Focal length Cost [€] resolution achieved by the microscope. Initially, the different [mm] Inc. tax diseases which had already been imaged with a smartphone- iPhone 5S rear camera 4.12 2.99 based microscope were collected. In addition, diseases that are iPhone 7 front camera 2.89 11.99 common in resource-limited regions were selected by using iPhone 5S front camera 2.15 2.90 the World Health Statistics 2018 of the World Health Samsung Galaxy S4 front camera 1.9 2.39 Organization (WHO) . Lastly, the diseases were filtered by those in which a diagnosis with the achieved smartphone- based microscope resolution was possible. The search engines GoogleScholar and Pubmed were used to find the publications. 2.2 Verification of the Optical System To determine the resolution of the system, images of a test target were recorded with four different configurations of the 3 Results smartphone-based microscope. The test target used was a MIL-STD-150A US Air Force optical resolution test target (see Fig. 2b). 3.1 Resolution and Field of View The resulting resolutions and the respective FOV of the lenses of different focal lengths are shown in Table 2. The highest individual resolution was achieved by using a Xiaomi Mi 8 Lite smartphone (Xiaomi Inc., Beijing, China) and the lens of the Samsung Galaxy S4 front camera. This configuration results in element 6 of group 8 being resolvable, which corresponds to a spatial resolution of 1.1 µm. Furthermore, the Samsung Galaxy S4 lens provided the highest resolution on Figure 2: (a) Smartphone-based microscope  (b) US Air Force average, with the nine different smartphones used. optical resolution test target. Table 2: Average optical magnification (M, see Eq. 1), mean Nine state of the art smartphones, all released after 2015, were minimal resolved element of group 8, resolution and field of view used to take images of the test target with each smartphone- (FOV) of the different smartphone-based microscope based microscope. This resulted in nine images per configurations, when using nine different state of the art microscope configuration. To determine the resolution of each smartphones. smartphone-based microscope the contrast gradient of every Smartphone module Ø M Element Resolution FOV element in group 8 of the test target is analysed. An element is (group 8) [µm] [mm²] considered resolved when the Michelson contrast was at least iPhone 5S (rear) -1 1 1.95 16.87 10 % in both, horizontal and vertical orientation. With the iPhone 7 -1.38 2 1.74 4.9 smallest resolvable element, the arithmetic mean of the iPhone 5S (front) -1.86 4 1.38 1.2 Michelson contrast was calculated for each smartphone-based Samsung Galaxy S4 -2.11 5 1.23 1.12 microscope. In order to determine the FOV, images of a 1 mm calibration target were taken. Using the recorded calibration Dorina Hasselbeck et al., Diagnostic Capabilities of a Smartphone-Based Low-Cost Microscope — 3 Technologies Co., Ltd., Shenzhen, China) and using the lens 3.2 Diagnostic Applications of a Samsung Galaxy S4 front camera. 26 different diseases were found that could be diagnosed by light microscopy and whose pathogens size enables a diagnosis with a smartphone-based microscope with a resolution of 1.23 µm or better. The potentially diagnosable diseases are listed in Table 3. Table 3: Overview of the diseases potentially diagnosable with the smartphone-based microscope without using immersion fluid and the respective pathogen structure size. Diseases marked with an asterisk are classified as an NTD. If only one dimension is given for the size, the pathogen usually has a long and slender shape. Disease Specimen Size [µm] Ref. Malaria Blood smear 1.5×1  Taeniasis* Stool sample 30  Enterobiasis Skin scraping 50×20  Figure 3: Images taken with transmitted illumination with the Fasciolosis* Stool sample 60×117  smartphone-based microscope of a giemsa stained blood smear Intestinal fluke infections* Stool sample 130  with erythrocytes infected with malaria plasmodium (bluish) where an accumulation of stain due to a crack in the cover plate can also Opisthorchiasis* Stool sample 30×12  be seen (a), a giemsa stained blood smear infected with microfilarie Paragonimiasis* Sputum sample 80  causing human African trypanosomiasis (b), a stool sample infected with eggs of the Trichuris Trichiura causing Trichuriasis (c), and a Loiasis Blood smear 290×7.5  stool sample infected with eggs of Taenia saginata causing Lymphatic filiariasis* Blood smear 250×10  Taeniasis (d). Mansonelliasis Blood smear 1.5×100  Onchocerciasis* Skin biopsy 220×5  Ascariasis* Stool sample 60×40  4 Discussion Trichuriasis* Stool sample 50×22  Schistosomiasis* Stool sample 83×60  The use of the Samsung Galaxy S4 front camera lens resulted in the highest resolution. This increase of resolution compared Hookworm disease* Stool sample 64×36  to the use of the other lenses is accompanied by a significant Strongyloidasis* Stool sample 6-13  reduction of the FOV. This reduction has a negative effect on Chagas disease* Blood smear 6-20  the sensitivity of a diagnosis. Human African Blood smear 10×40  However, only with this higher resolution, the widespread trypanosomiasis* disease Malaria (pathogen size 1.5 µm) is diagnosable. This is Amoebiasis Stool sample 10-20  especially significant given the fact that there were an Balantidiasis Stool sample ≤150  estimated 216 million cases worldwide causing approximately Giadiasis Stool sample 9×5  445,000 deaths in 2016 , of which the majority occurred in resource-limited regions. Additionally, a variety of diseases Leishmaniasis* Skin biopsy 1.8-2  that are categorised as neglected tropical diseases (NTDs) Scabies* Skin scraping 300×250  cause serious problems in the same regions with 1 billion Sickle cell anemia Blood smear 7.5  infected people worldwide and an estimated number of Iron deficiency anemia Blood smear 7.5  534.000 deaths per year. The reason for the neglect of this Hematuria Blood smear 7.5  diseases is often a lack of financial resources . An overall number of 16 NTDs are diagnosable with the described smartphone-based microscope. 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Current Directions in Biomedical Engineering – de Gruyter
Published: Sep 1, 2020
Keywords: Smartphone-based Microscope; Diagnostics; Malaria; Parasites; Neglected Tropical Diseases (NTDs)
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