LitCovid-sentences  

PMC:7143804 / 981-13453 JSONTXT 12 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T9 0-2 Sentence denotes 1.
T10 3-15 Sentence denotes Introduction
T11 16-76 Sentence denotes Diseases were and can still be a major problem in the world.
T12 77-112 Sentence denotes Examples are outbreaks of zoonoses.
T13 113-208 Sentence denotes One very recent example is the Covid-19 coronavirus outbreak in the People’s Republic of China.
T14 209-272 Sentence denotes Zoonoses are also a widespread problem in animal husbandry [1].
T15 273-399 Sentence denotes This group encompasses diseases which can be transferred between animals (usually vertebrates) and between animals and humans.
T16 400-501 Sentence denotes They are transmitted through zoonotic agents (e.g., bacteria, viruses, fungi, and parasites) [2,3,4].
T17 502-765 Sentence denotes Examples of bacterial zoonoses are the infections caused by Coxiella burnetii (Q-fever), Mycobacterium bovis (bovine tuberculosis), and by species of the Salmonella (Salmonellosis), Campylobacter (Campylobacteriosis), and Escherichia (Escherichiasis) genus [2,5].
T18 766-837 Sentence denotes These diseases are of potential risk for humans and livestock of farms.
T19 838-957 Sentence denotes Poon et al. show that early-stage detection of coronaviruses positively influence the survival chances of patients [6].
T20 958-1103 Sentence denotes An outbreak among the livestock of a farm is often disastrous to the owner of that farm, and for people living in the proximity of that farm [7].
T21 1104-1258 Sentence denotes Often, more animals of the livestock are infected and the whole livestock is exterminated out of precaution, which could lead to bankruptcy of the farmer.
T22 1259-1392 Sentence denotes Therefore, early-stage detection of this group of diseases, and other diseases as well, is often the key to save lives and livestock.
T23 1393-1562 Sentence denotes As these diseases are also encountered at remote locations and in developing countries, it is desired that such detection equipment is portable and as cheap as possible.
T24 1563-1631 Sentence denotes A lab-on-a-chip platform can be used for this early-stage detection.
T25 1632-1820 Sentence denotes In the early stage of diseases, the agent, and therefore its genetic material, is only present in low concentrations within the infected human or animal, making detection rather difficult.
T26 1821-2104 Sentence denotes One way to overcome this low concentration is to amplify the genetic material of the agent, i.e., deoxyribonucleic acid (DNA) in case of bacteria and DNA or ribonucleic acid (RNA) in case of viruses, until a certain threshold is reached and detection of the disease is made possible.
T27 2105-2466 Sentence denotes When this amplification reaction is specific to certain DNA or RNA sequences, for example, by using polymerase chain reaction (PCR) [6,8], helicase-dependent amplification (HDA) [9,10], or loop-mediated isothermal amplification (LAMP) [11], and when a fluorescent DNA or RNA binding dye is used, a simple yes-or-no answer for a specific disease can be obtained.
T28 2468-2472 Sentence denotes 1.1.
T29 2473-2489 Sentence denotes State-of-the-Art
T30 2490-2569 Sentence denotes In the past, several chip-based DNA and RNA amplification devices are reported.
T31 2570-2677 Sentence denotes It goes beyond the scope of this paper to discuss the state-of-the-art of DNA amplification chips in-depth.
T32 2678-2766 Sentence denotes There are several good review papers written on this topic [12,13,14,15,16,17,18,19,20].
T33 2767-2839 Sentence denotes Readers are referred to these for a comprehensive overview of the field.
T34 2840-3030 Sentence denotes In this paper, the state-of-the-art is divided into several discussion points, i.e., the heating method, the temperature control method, and the substrate material and fabrication technique.
T35 3031-3073 Sentence denotes These points will be discussed separately.
T36 3074-3140 Sentence denotes With respect to heat supply, different methods have been employed.
T37 3141-3253 Sentence denotes Almassian et al. give a comprehensive overview of different possible heating methods in their review paper [12].
T38 3254-3403 Sentence denotes Not all of the mentioned methods are easy to implement in low-cost and portable lab-on-a-chip devices due to their bulkiness or implementation costs.
T39 3404-3513 Sentence denotes Examples of these rather difficult methods are using heating via induction, infrared, or microwave radiation.
T40 3514-3641 Sentence denotes Others are not useful due ot their challenging temperature control, like with heating up the system using exothermic reactions.
T41 3642-3725 Sentence denotes Within the field of DNA amplification, different mechanisms of amplification exist.
T42 3726-3811 Sentence denotes Some are based on thermo cycling processes, e.g., PCR, whereas others are isothermal.
T43 3812-3899 Sentence denotes The use of an isothermal amplification technique puts less requirements on the heaters.
T44 3900-4093 Sentence denotes Isothermal processes are either truly isothermal or consisting of three different temperatures, as they have a thermal denaturation step before and a termination step after the elongation step.
T45 4094-4243 Sentence denotes The switching between these temperature steps does not have to be as fast as with thermal cycling steps in, for example, PCR amplification reactions.
T46 4244-4376 Sentence denotes The use of less temperature variations makes it easier to maintain the set temperature as there is less heating an cooling involved.
T47 4377-4501 Sentence denotes Furthermore, it eliminates the use of a continuous flow approach in systems with low thermal conductivities, e.g., polymers.
T48 4502-4576 Sentence denotes Therefore, it is easier to implement within lab-on-a-chip devices [17,21].
T49 4577-4734 Sentence denotes Isothermal DNA amplification reactions can already be performed by putting the chip on a commercially available hotplate [22,23] or Peltier elements [24,25].
T50 4735-4796 Sentence denotes However, these heating systems are bulky and power-consuming.
T51 4797-4884 Sentence denotes Therefore, they are not useful for portable equipment or operation at remote locations.
T52 4885-4950 Sentence denotes Miniaturizing heaters lowers the bulkiness and power consumption.
T53 4951-5139 Sentence denotes Miniaturized heaters can be integrated as integrated resistive heaters, e.g., as deposited thin-film metal [26,27,28,29] or as laminated Cu foil [30], or as micro-Peltier elements [31,32].
T54 5140-5319 Sentence denotes These miniaturized heaters can be implemented directly onto the microfluidic chip [28] or on a different substrate and leter incorporated onto the microfluidic chip [33,34,35,36].
T55 5320-5443 Sentence denotes The geometry of such a heater contributes significantly to the uniformity of the heat distribution within the chip [26,37].
T56 5444-5570 Sentence denotes One method to accurately control the temperature is the use of a proportional-integral-derivative (PID) controlled thermostat.
T57 5571-5703 Sentence denotes These PID controllers are coupled to the electrical heaters and use a thermocouple as feedback-loop to the controller [22,23,24,25].
T58 5704-5813 Sentence denotes There are various materials that can be used to fabricate lab-on-a-chip devices for DNA or RNA amplification.
T59 5814-5949 Sentence denotes In the past 15 years, more than ten polymers, ceramic materials, and metals have successfully been used to fabricate such devices [15].
T60 5950-6029 Sentence denotes The major property playing a role here is the biocompatibility of the material.
T61 6030-6118 Sentence denotes The surface of the microfluidic structure should not inhibit the amplification reaction.
T62 6119-6272 Sentence denotes This biocompatibility can be an intrinsic property of the material or the surface can be modified or coated to achieve this [12,13,14,15,16,17,18,19,20].
T63 6273-6403 Sentence denotes One often used material is polydimethylsiloxane (PDMS) [22,23,31,32,34,35,38], which can be processed using soft lithography [39].
T64 6404-6521 Sentence denotes However, this is a fabrication technology used in academia and is not suitable for upscaling to mass production [40].
T65 6522-6625 Sentence denotes Fabrication methods suitable for mass production are thermoforming/embossing or injection molding [41].
T66 6626-6845 Sentence denotes One of the materials which is biocompatible and suitable for both industrial scale fabrication technologies is cyclic olefin copolymer (COC) [42], which is one of the materials used in the past as well [28,36,43,44,45].
T67 6846-7026 Sentence denotes Guckenberger et al. estimates the costs of injection molding of only 50 simple microfluidic devices on $47, but this becomes cheaper when the mass production stage is reached [41].
T68 7027-7100 Sentence denotes Another benefit of COC is the possibility to shape it using micromilling.
T69 7101-7214 Sentence denotes This technique is a rapid prototyping technology and therefore very useful within proof-of-concept projects [41].
T70 7215-7303 Sentence denotes Integrating resistive metal tracks onto a COC substrate have also been done in the past.
T71 7304-7523 Sentence denotes Some papers describe the use of a surface modification step done before metal deposition in order to enhance adhesion between the COC and the metal layer, like a pretreatment with plasma [46] or an organic solvent [47].
T72 7524-7606 Sentence denotes Other papers describe the direct deposition of metal onto the COC surface [28,48].
T73 7607-7706 Sentence denotes Chung et al. specifically, fabricated an amplification chip in COC with integrated Au heaters [28].
T74 7707-7837 Sentence denotes However, their system required heating from both sides as the used grade of COC has a glass transition temperature (Tg) of 130 °C.
T75 7838-7941 Sentence denotes This COC could not withstand the required heater temperatures to have enough heat flux into the system.
T76 7942-8076 Sentence denotes They had to heat up the heater to temperatures above 130 °C, which caused cracking of the heater tracks due to deformation of the COC.
T77 8077-8181 Sentence denotes With their double-sided heating they ensured that the reaction mixture had the desired PCR temperatures.
T78 8182-8336 Sentence denotes However, double-sided heating doubles the amount of metal required, increases the amount of fabrication steps, and therefore increases the price per chip.
T79 8338-8342 Sentence denotes 1.2.
T80 8343-8361 Sentence denotes The Presented Work
T81 8362-8715 Sentence denotes The work presented at the 4th Microfluidic Handling Systems conference and which is extended in this paper aims at the development of a disposable, polymer-based DNA amplification lab-on-chip system with integrated resistive heater based on the World Health Organization (WHO) Sexually Transmitted Diseases Diagnostics Initiative (SDI) ASSURED criteria.
T82 8716-8903 Sentence denotes Devices which are ASSURED are (A) affordable, (S) sensitive, (S) specific, (U) user-friendly, (R) robust and rapid, (E) equipment-free, and (D) deliverable to those who need them [20,49].
T83 8904-8979 Sentence denotes The first step towards such a device is the development of the chip itself.
T84 8980-9079 Sentence denotes This paper focuses on the choice of substrate material, metal deposition method, and type of metal.
T85 9080-9237 Sentence denotes Although, it is mentioned above that PCR and HDA are sequence specific, the reaction chosen is the isothermal multiple displacement amplification (MDA) [50].
T86 9238-9516 Sentence denotes This reaction is more straightforward [51], as it amplifies any present DNA, and is therefore better suitable as a proof-of-principle amplification reaction to show the functioning of the integrated heater and the biocompatibility of the substrate after the fabrication process.
T87 9517-9656 Sentence denotes The use of an isothermal amplification technique also simplifies the final device and lowers its footprint, as there are no pumps required.
T88 9657-9812 Sentence denotes In this research, external analysis methods are used which do not contribute to the WHO-SDI ASSURED criteria due to their bulkiness, costs, and difficulty.
T89 9813-9939 Sentence denotes However, suggestions and comments on the integration of low-cost detection methods, which are ASSURED, are given in Section 5.
T90 9941-9945 Sentence denotes 1.3.
T91 9946-9981 Sentence denotes Multiple Displacement Amplification
T92 9982-10135 Sentence denotes The proof-of-principle amplification of choice is a MDA reaction, which is a non-specific isothermal method of amplification performed around 30 °C [50].
T93 10136-10226 Sentence denotes MDA is a method of whole genome amplification (WGA), as it amplifies all present DNA [52].
T94 10227-10297 Sentence denotes It is commonly used when the initial amount of DNA sample is very low.
T95 10298-10433 Sentence denotes After the WGA is performed, a sequence specific amplification can be done since the quality the amplified DNA by MDA is very high [53].
T96 10434-10570 Sentence denotes The amplification reaction is illustrated below in Figure 1 (the contour of the amplified sequence is highlighted in black for clarity).
T97 10571-10787 Sentence denotes Starting with a double stranded DNA (dsDNA) molecule, a denaturation step at 95 °C is required, giving the random hexamer-primers and the ϕ29 DNA polymerase access to the bases of single stranded DNA (ssDNA) strands.
T98 10788-10857 Sentence denotes The hexamers anneal themself to aleatory parts of the ssDNA sequence.
T99 10858-10926 Sentence denotes These hexamers work as initiation sites for the ϕ29 DNA polymerases.
T100 10927-11041 Sentence denotes After denaturation at 95 °C, the mixture is cooled down to ice temperature and the rest of the reagents are added.
T101 11042-11242 Sentence denotes The mixture is heated up to ~30 °C so the polymerase starts to complete the complementary ssDNA sequence, creating again a dsDNA strand, eventually it encounters a hexamer from another annealing site.
T102 11243-11380 Sentence denotes Once this happens the polymerase will lift up that hexamer and starts to separate the amplified sequence formed from that annealing site.
T103 11381-11478 Sentence denotes As the polymerase displaces the formed strand ahead of it, it continues to complete the sequence.
T104 11479-11698 Sentence denotes The displaced strand becomes a new ssDNA strand and therefore, it gives new sites for more primers to attach and initiation sites for the polymerase, continuing the amplification, and thus creating a web of DNA strands.
T105 11699-11785 Sentence denotes Finally, the inactivation of the polymerase is done by heating up the system to 65 °C.
T106 11786-12030 Sentence denotes Even though MDA is considered an isothermal process, prior to the reaction and to the addition of most reactants, the dsDNA and a buffer are heated up to 95 °C to denature the dsDNA to ssDNA and to give hexamers the initial access to the ssDNA.
T107 12031-12111 Sentence denotes After the amplification reaction, the polymerase has to be inactivated at 65 °C.
T108 12112-12255 Sentence denotes However, this does not require fast temperature changes, as would be the case with, for example, the temperature cycling in PCR amplifications.
T109 12256-12472 Sentence denotes This, together with the robustness of the amplification (it is a self-limiting reaction that amplifies all present DNA [50]) makes MDA perfectly suitable as proof-of-principle amplification reaction for such devices.