4.1. Bulk temperature

The bulk temperatures of liquids in microfluidic systems are uniformly distributed and it can be changed by either external heating or internal heating approaches. A number of techniques have been implemented for various applications.

compact setup is able to complete 10 thermal cycles within 20 min. With the similar configuration, Yang et al. [55] fabricated a serpentine microchannel on a thin polycarbonate plate (thickness: 0.75 mm) as a PCR microreactor (Figure 5). They used thermocouples to measure the surface temperatures of the intrachamber temperature and Peltier elements. With the developed device, they performed 30 thermal cycles in 30 min and the heating rate and cooling

Figure 5. (a) Peltier thermocycler for the PCR microreactor and (b) a photograph of the serpentine polycarbonate

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Furthermore, Maltezos et al. [62] chose using liquid metal in combination with Peltiers to explore the limits of PCR speed in a microchip. Sample tubes were first immerged in a liquid medium (gallium eutectic) and then sandwiched between two high-powered Peltier elements. Heat can be rapidly transferred between the DNA/RNA in the sample tubes and the Peltier elements via the liquid interface. High heating rate and cooling rate can be up to 106 and 89C/s

On the other side, the direct integration of heating or cooling elements into microfluidic systems is a popular method. Integrated heating approaches are able to reduce the whole

Joule heating has been the most widely-used technique as an integrated heating solution for the temperature control in microfluidic systems. Lao et al. [63] filled platinum into siliconbased microchannels as in-chip heaters and sensors. A well-controlled thermal environment (1C) was achieved for gas and liquid phase reactions (Figure 6). The silicon microchannel was thermally isolated by a thin silicon nitride membrane to save power consumption. Precise and prompt temperature control was facilitated with a digital feedback system developed by them (heating rate: 20C/s, cooling rate: 10C/s, and response time: 5 s). By using similar serpentine channel configurations, Wu et al. [64] injected silver paint into the PDMS microchannels as integrated microheaters and took an advantage of compressed air for rapid cooling in parallel channels. Heating rate was 20C/s and error of temperature was about 0.5C in the steady state. With this device, DNA can be successfully amplified in 25 thermal cycles with 1 min per cycle. Instead of applying metal, de Mello et al. [65] made use of ionic

rate are 7–8 and 5–6C/s, respectively.

microchannel [55].

in their experiments, respectively.

system size and improve its portability.

To control the bulk temperature of the liquids, the external heating approaches usually use either commercial heaters (e.g., Peltier elements) or preheat/cool liquids prior to being injected into microchannels. Velve Casquillas et al. [60] designed an external temperature control system with two Peltier elements that is able to readily vary the temperature of yeast channel underneath the temperature control channel (shown in Figure 4a). By using this system, they can rapidly regulate the yeast channel temperature in a wide range (5–45C within 10 s). Similarly, Khandurina et al. [61] utilised two Peltier elements as a sandwich assembly to directly heat up a microfluidic chip for the polymerase chain reaction (PCR) (Figure 4b). This

Figure 4. (a) A schematic of the temperature control device by an external Peltier element; the yeast channel is placed below the temperature control channel [60] and (b) schematic of the dual Peltier assembly for rapid thermal cycling followed by electrophoretic analysis on-chip [61].

stress between the polymer molecules, the quantity or coverage of polymer molecules on each

Temperature is a crucial parameter in many microfluidic applications, for example, microscale milk pasteurisation unit [53], polymerase chain reaction (PCR) [54, 55], mixing [56], and temperature gradient focusing [57] or separation [58]. Lab-on-a-chip devices and systems are compact and multi-functional platforms which can be integrated into a small chip. Temperature control is one of the important functions in various microfluidic applications. In this section, different techniques for temperature control in microfluidic systems will be summarised into

The bulk temperatures of liquids in microfluidic systems are uniformly distributed and it can be changed by either external heating or internal heating approaches. A number of techniques

To control the bulk temperature of the liquids, the external heating approaches usually use either commercial heaters (e.g., Peltier elements) or preheat/cool liquids prior to being injected into microchannels. Velve Casquillas et al. [60] designed an external temperature control system with two Peltier elements that is able to readily vary the temperature of yeast channel underneath the temperature control channel (shown in Figure 4a). By using this system, they can rapidly regulate the yeast channel temperature in a wide range (5–45C within 10 s). Similarly, Khandurina et al. [61] utilised two Peltier elements as a sandwich assembly to directly heat up a microfluidic chip for the polymerase chain reaction (PCR) (Figure 4b). This

Figure 4. (a) A schematic of the temperature control device by an external Peltier element; the yeast channel is placed below the temperature control channel [60] and (b) schematic of the dual Peltier assembly for rapid thermal cycling

two categories: bulk temperature control and temperature gradient control [59].

solid surface and solid surfaces (i.e., reversible process or not) [49–52].

4. Temperature control in microfluidic systems

have been implemented for various applications.

followed by electrophoretic analysis on-chip [61].

4.1. Bulk temperature

112 Microfluidics and Nanofluidics

Figure 5. (a) Peltier thermocycler for the PCR microreactor and (b) a photograph of the serpentine polycarbonate microchannel [55].

compact setup is able to complete 10 thermal cycles within 20 min. With the similar configuration, Yang et al. [55] fabricated a serpentine microchannel on a thin polycarbonate plate (thickness: 0.75 mm) as a PCR microreactor (Figure 5). They used thermocouples to measure the surface temperatures of the intrachamber temperature and Peltier elements. With the developed device, they performed 30 thermal cycles in 30 min and the heating rate and cooling rate are 7–8 and 5–6C/s, respectively.

Furthermore, Maltezos et al. [62] chose using liquid metal in combination with Peltiers to explore the limits of PCR speed in a microchip. Sample tubes were first immerged in a liquid medium (gallium eutectic) and then sandwiched between two high-powered Peltier elements. Heat can be rapidly transferred between the DNA/RNA in the sample tubes and the Peltier elements via the liquid interface. High heating rate and cooling rate can be up to 106 and 89C/s in their experiments, respectively.

On the other side, the direct integration of heating or cooling elements into microfluidic systems is a popular method. Integrated heating approaches are able to reduce the whole system size and improve its portability.

Joule heating has been the most widely-used technique as an integrated heating solution for the temperature control in microfluidic systems. Lao et al. [63] filled platinum into siliconbased microchannels as in-chip heaters and sensors. A well-controlled thermal environment (1C) was achieved for gas and liquid phase reactions (Figure 6). The silicon microchannel was thermally isolated by a thin silicon nitride membrane to save power consumption. Precise and prompt temperature control was facilitated with a digital feedback system developed by them (heating rate: 20C/s, cooling rate: 10C/s, and response time: 5 s). By using similar serpentine channel configurations, Wu et al. [64] injected silver paint into the PDMS microchannels as integrated microheaters and took an advantage of compressed air for rapid cooling in parallel channels. Heating rate was 20C/s and error of temperature was about 0.5C in the steady state. With this device, DNA can be successfully amplified in 25 thermal cycles with 1 min per cycle. Instead of applying metal, de Mello et al. [65] made use of ionic

4.2. Temperature gradient

For several applications such as Soret effect and droplet actuation, temperature gradients are demanded in microfluidic systems. Temperature gradients have been generated in either a

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As illustrated in Figure 8a, Mao et al. [67] generated a linear temperature gradient along the horizontal direction of the PDMS microchannel by using the pre-heated liquid approach. Hot and cold fluids were channelled into two side channels separately, and a stable temperature gradient has been established in the central channel (Figure 8b). Zhao et al. [68] implemented this approach for studies on thermophoresis using a microchip made of stainless steel. Due to a higher conductivity of stainless steel than PDMS, a wider range of variations for both bulk temperature and temperature gradient (1.5 104 K/m) can be formed in the microchannel. In order to fabricate similar structures in PDMS microchip, Yan et al. [69] proposed a fast prototyping method for single-layer PDMS microfluidic devices with abrupt depth variations by combining the laser ablation and NOA81 moulding. The whole fabrication process can be completed within 2 h. This method can readily produce PDMS microfluidic devices with micrometre and millimetre structures in one step. Moreover, this method can be applied in a non-clean-room environment and does not require complicated and expensive soft lithography equipment or etching processes.

Instead of preheating liquids, Vigolo et al. [70] chose to use silver-filled epoxy with a similar parallel channel configuration to generate temperature gradients in a microchannel. This microscale heating element can be powered by two ordinary AAA batteries. Thus, this design shows its potential as a cost effective and portable solution for thermal control of microfluidic devices. Alternatively, the parallel-channel configuration has also been implemented for control of bulk temperatures in microchannels. It can be readily realised by changing the direc-

In addition to regulating bulk temperatures, Peltier elements can be utilised to establish a constant temperature gradient in microfluidic systems. Matsui et al. [74] designed and fabricated a hybrid temperature gradient focusing (TGF) chip (materials: PDMS/glass) by applying two Peltier elements. A range of temperature gradient can be formed along the horizontal

Figure 8. (a) Schematic diagram of a device with an on-chip linear temperature gradient and (b) a plot of temperature vs.

controlled temperature profile or an arbitrary way by various techniques.

tions of preheated liquid and DC electric current [71–73].

position of the temperature gradient device [67].

Figure 6. Top view of the microchip showing the patterned heaters and temperature sensors [63].

liquids ([BMIM][PF6] and [BMIM][Tf2N]) as heating elements. The ionic liquid was Joule heated by an AC current (power: 1 W, frequency: 50 Hz, and voltage: ≤ 3.75 kV). By controlling the applied voltage of the ionic liquids, the bulk temperature was regulated from 50 to 90C with an accuracy of 0.2C.

Other than the commonly used physical heating approach (i.e., Joule heating), chemical approach can be another integrated option. To locally control the temperature in a microchannel, Guijt et al. [66] made use of heat adsorption and dissipation via endothermic and exothermic chemical reactions, respectively (Figure 7a). Heating/cooling can be achieved in a temperature control channel (TCC) where two reagents from separate reactant channels (RC1 and RC2) merged and had chemical reaction. Heating was achieved with a dissolution of 97 wt% H2SO4 (Reagent 1) in water (Reagent 2), while cooling was realised with the evaporation process acetone (Reagent 1) in the air (Reagent 2). A wide temperature range from 3 to 76C with a ramp rate of 1C/s can be realised in the central channel by manipulating the flow rate ratio between two reagents (shown in Figure 7b).

Figure 7. (a) Two reactant channels (RC) merging into a temperature control channel (TCC) and (b) layout of the device used for demonstration experiments [66].
