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Diagnosis: Nanosensors in Diagnosis and Medical Monitoring
Published in Harry F. Tibbals, Medical Nanotechnology and Nanomedicine, 2017
In microfluidic chips, MEMS micropumps and microvalves have been used to drive and control the flow of analytes and reagents. Since the channels are capillary sized, samples can be kept separated within the microscopic flow channels by air bubbles. Alternatively, aqueous microsample alli-quoits, labeled beads, or cells can be separated by suspension as droplets or particles in a stream of oil [213]. But newer microfluidic technology is obviating the need for micropumps and valves, and is instead controlling the movement of droplets by optical and electromagnetic forces. This newer version of microfluidics is called electrokinetics, or digital microfluidics [214-216].
Advanced Biotechnology
Published in Lawrence S. Chan, William C. Tang, Engineering-Medicine, 2019
Another major area of advances that is made possible by the miniaturization capabilities of MEMS is Lab-on-a-Chip. As the name implies, this field is characterized by drastic miniaturization of forms and functions of a conventional chemical, biological, or clinical laboratory onto a chip-scale platform. It is a device enabled by MEMS that integrates one or several laboratory functions onto a chip from few millimeters to a few centimeters on a side (Volpatti and Yetisen 2014). The advantages of reducing a roomful of instruments in a conventional laboratory onto a chip with integrated smart electronics include drastic reduction in cost of the platform and the functions they perform, reduction in sample size and consumables, speed in achieving test results, automation, and massively deployable and widely accessible. The demand and rapid growth of the Lab-on-a-Chip field is captured by the establishment and success of one of the premier journals in the field, Lab on a Chip, published by the Royal Society of Chemistry (RSC.org). The journal was first introduced in 2001, and now carries an Impact Factor of 5.995. It comprehensively represents the field on novel micro- and nano-technologies and fundamental principles including (RSC.org) Micro- and nano-fabrication (including 3D printing, thin films).Micro- and nano-fluidics (in continuous and segmented multiphase flow, droplet microfluidics, new liquids).Micro- and nano-systems (sensor, actuator, reaction).Micro- and nano-separation technologies (molecular and cellular sorting).Micro- and nano-total analysis system (µTAS, nTAS).Digital microfluidics.Sample preparation.Imaging and detection.
Metabolomics in antimicrobial drug discovery
Published in Expert Opinion on Drug Discovery, 2022
Compared to GC-MS and NMR, LC-MS is the most widely used technique due to the wealth of information it is capable of providing as well as due to its sensitivity, flexibility, and versatility. Developments in this technology include the use of smaller particle-size packed columns, decreasing mobile-phase viscosity, and optimization of column technology to improve the efficiency of separation by reducing eddy and longitudinal diffusion and improving mass-transfer resistance [3]. The use of multi-dimensional separations such as two-dimensional LC may also improve separation efficiencies and extend the coverage of metabolites. Other developments in the field include integration of microfluidic and digital devices with MS, which, due to miniaturization, allows incorporation of different components performing sample preparation, separation, and introduction steps. Commercially available devices include IonKey (Waters) and HPLC-Chip (Agilent), chipLC-ESI devices, and the ZipChip (908 Devices) chipCE-ESI device [3]. Integration of digital microfluidics platforms with MS offers even further miniaturization, smaller sample size, faster analysis, high-throughput, and automation.
Label-free plasmonic biosensors for point-of-care diagnostics: a review
Published in Expert Review of Molecular Diagnostics, 2019
Maria Soler, Cesar S. Huertas, Laura M. Lechuga
Microfluidic systems intended for the POC plasmonic devices must employ simple and ideally automated operational principles, be compatible with light pathways (i.e. optically transparent), be fabricated with low-cost and scalable techniques, and should enhance the biosensing performance. The latter can be attempted by ensuring an efficient sample delivery, minimizing reagent and sample consumption, and enabling high-throughput and multiplexed analyses. Conventional microfluidics are usually fabricated as multilayered polymeric devices with input and transport channels – of several micrometers of size – and an output to a waste reservoir [24]. These systems generally are operated with the help of syringe or peristaltic pumps that provide a continuous and regular flow of the sample over the sensor. The simplicity of such design allows for including multiple channels, which can be further controlled with pneumatic or mechanic valves, for parallel multiplexed analysis. In this regard, Chen et al. developed a microfluidic patterning technique with 10 segments of six collocating parallel detection spots for the detection of inflammatory cytokines in serum (Figure 3(a)) [25]. Acimovic et al. reported an LSPR-based multiplexed detection platform with up to 32 sensing sites on a single sensor [26]. In their latest article, this system has been employed for the direct detection of different cancer biomarkers in human serum, proving the potential for disease diagnostics [27]. However, these biosensors still require bulky equipment (e.g. microscopes, spectrometers, etc.) not appropriate for POC settings. Another microfluidic approach to improve the biosensing performance is to exploit the nanoplasmonic structures for fluid manipulation. It is the case of flow-through schemes utilizing plasmonic nanoapertures as nanochannels, which has been employed for capturing pathogens specifically around the detection hot spots [28]. Finally, on the road toward full automation of microfluidics, numerous strategies are continuously developing including microreactors, droplet-based techniques, digital microfluidics, etc. [29–31]. Although the integration of these advanced fluid-control methodologies with plasmonic biosensors does not seem to be easy, ongoing research and future perspectives can anticipate an enormous boost of lab-on-a-chip POC diagnostics with the synergy of both technologies.
Digital microfluidics comes of age: high-throughput screening to bedside diagnostic testing for genetic disorders in newborns
Published in Expert Review of Molecular Diagnostics, 2018
David Millington, Scott Norton, Raj Singh, Rama Sista, Vijay Srinivasan, Vamsee Pamula
The theory of digital microfluidics (DMF) and its applications have been reviewed [1]. The principles and development of electrowetting-based digital microfluidic devices to provide a practical and effective platform upon which to base a wide variety of clinically useful tests was reviewed by Pollack, et al. several years ago [2]. This review article described the ‘lab-on-a-chip’ system, conceived of and developed by Advanced Liquid Logic, Inc., that permitted the manipulation of micro-droplets on a disposable printed circuit board (PCB) with built-in reservoirs for samples, reagents, and waste by software control, such that all the steps required for an enzymatic assay, for example, were performed programmatically. The versatility of this platform to perform assays of interest to the newborn screening (NBS) community was explored at about this time [3]. There was considerable interest in expanding the range of NBS testing in dried blood spots (DBS) to include certain lysosomal storage disorders (LSDs) that were considered treatable [4,5]. Screening for LSDs was initially suggested by Chamoles, et al., who developed several fluorogenic enzymatic assays to test DBS samples in 96-well microtiter plates using a benchtop microfluorometer [6–8]. Chamoles used existing fluorogenic substrates that were already in use in diagnostic laboratories and translated those to the microtiter plate format. Subsequently, tandem mass spectrometry (MS/MS) methods for LSD enzyme measurement that used non-fluorometric synthetic substrates were developed [9–11]. The initial translation of fluorometric enzyme assays for selected LSDs onto the DMF platform [12] took advantage of the fact that up to eight assays on each of 12 samples could potentially be performed within a single run on the same platform. A prototype instrument was developed and used in a pilot NBS program in Illinois to prospectively screen for three LSDs [13]. However, it was the development of a cartridge capable of performing at least 5 assays on up to 48 samples that launched high-throughput NBS for LSDs using the DMF platform [14]. The state of Missouri became the first NBS program in the United States to prospectively screen all newborns for four LSDs using the SEEKER DMF platform with novel reagents supplied by the manufacturer [15]. The fact that it is still doing so with no significant problems, changes or improvements testifies to the robustness of the platform. The acquisition of Advanced Liquid Logic by Illumina [16] resulted in a hiatus of approximately 2 years in further clinical DMF assay development until a new company, Baebies Inc., was founded in late 2014. In February 2017, SEEKER became the first and currently remains the only United States Food and Drug Administration (FDA) authorized platform to screen newborns for LSDs [17]. It was also the first DMF device to be cleared by the FDA for clinical applications. Future development of this technology is expected to expand the menu of available assays for high-throughput NBS. The technology is also being miniaturized to support rapid, comprehensive diagnostic testing of critical neonatal conditions such as hyperbilirubinemia, hypothyroidism, hypoglycemia, and hypercoagulation near the patient using small sample volumes.