Smartphone technology facilitates point-of-care nucleic acid diagnosis: a beginner’s guide

Sample Preparation and Diagnostic Methods for a Variety of Settings: A Comprehensive Review

“…This has led to the increased use and development of diagnostic methods to streamline the process and improve patient outcomes by decreasing the time needed to identify the cause of an infection, determine whether it is a resistant strain, and adjust patient treatment [ 27 , 28 , 29 ]. This vast range of techniques and their utility in identifying not only infectious diseases but also non-transmissible conditions can be attributed to the progress in technologies that support precision medicine over the last decade, including advances in microfluidic devices [ 30 , 31 , 32 , 33 , 34 ], next-generation sequencing (NGS) and nucleic acid amplification (NAA) methods [ 35 , 36 , 37 , 38 ], mass spectrometry (MS) techniques [ 29 , 38 , 39 , 40 ], laboratory automation [ 41 ], power sources for medical devices [ 42 ], smart materials and nanomaterials for imaging and sensing [ 8 , 43 , 44 , 45 ], biosensing technologies [ 34 , 43 , 46 , 47 , 48 , 49 , 50 ], smart devices for providing mobile power sources and computing power [ 50 , 51 , 52 , 53 ], data analysis techniques such as machine learning (ML) [ 54 , 55 , 56 , 57 ], and improved modeling of disease spread [ 58 ].…”

“…Regardless of the testing setting or method used, however, sample preparation is required. POCT in particular often faces additional challenges compared with the laboratory-scale testing methods that many methods are based on since clinical samples collected from patients at the POC are often in complex matrices such as whole blood, urine, or saliva, and any sample preparation has to be easily performed at the POC [ 53 , 67 , 72 ].…”

“…Since much of this sample preparation process is either impractical for use in POCT methods or has a much longer turnaround time as well as less sensitivity and specificity than biochemical or molecular diagnostic laboratory methods, many of the methods developed over the past decade have focused on either making the extraction and separation steps compatible with POC platforms or increasing the sample throughput of biochemical and molecular diagnostic methods used in clinical laboratory platforms [ 21 , 24 , 25 , 26 , 27 , 28 , 29 , 38 , 39 , 41 , 46 , 66 , 70 ]. As previously mentioned, the large number of advances in areas such as microfluidics, advanced materials, and biosensors, as well as the growing ubiquity of smartphones, has greatly supplemented this process for POC devices and methods while advances in laboratory automation, extractions and separations, and high-throughput assay platforms, such as microplates, have analogously supplemented the process for centralized laboratory methods, as shown in Figure 4 [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ]. For molecular methods, including NAATs in particular, the greatest bottleneck in this process usually consists of extracting the target biomarkers by lysing the pathogens in a collected sample and separating or purifying the target analytes in order to proceed to amplification or detection [ 26 , ...…”

“…As previously mentioned, the large number of advances in areas such as microfluidics, advanced materials, and biosensors, as well as the growing ubiquity of smartphones, has greatly supplemented this process for POC devices and methods while advances in laboratory automation, extractions and separations, and high-throughput assay platforms, such as microplates, have analogously supplemented the process for centralized laboratory methods, as shown in Figure 4 [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ]. For molecular methods, including NAATs in particular, the greatest bottleneck in this process usually consists of extracting the target biomarkers by lysing the pathogens in a collected sample and separating or purifying the target analytes in order to proceed to amplification or detection [ 26 , 37 , 53 , 58 , 67 ]. In response to this, a great number of extraction/lysis methods have been developed for use in tandem with diagnostic methods utilizing nucleic acids as the target biomarkers, as they are both simple to apply to POC settings while maintaining sensitivity and specificity and are amenable to scaling up for high-throughput clinical laboratory testing for a large number of pathogens [ 21 , 26 , 74 , 75 , 76 , 77 , 78 ].…”

“…Just as many cartridge and chip systems that integrate sample preparation and detection into one device have been developed, many standalone systems for sample preparation steps such as extraction and separations have as well. As mentioned previously, the extraction of target analytes such as nucleic acids or antibodies from clinical samples is often the primary goal of any extraction steps involved in sample preparation [ 9 , 10 , 14 , 26 , 37 , 53 , 57 , 67 , 77 , 80 , 124 ]. To accomplish this, several different approaches to extraction/lysis of pathogens have been developed, including chemical, enzymatic, mechanical, sonication, thermal, electrical, and focused radiation methods [ 74 , 76 , 125 , 126 ].…”