*3.3.1 Adhesive bonding*

Adhesive bonding is a simple manner to seal microfluidic devices, compared to other bonding techniques. By applying the liquid adhesive onto the surface of the chips, the solvent composition starts to evaporate till two parts are bonded. Besides, some adhesives with epoxy or acrylate compositions need to be cured under UV light irradiation or upon heating. After mixing with the photo-initiator or catalyzing agent, polymerization or crosslink reaction can occur in the adhesive system [56], where the adhesive is cured and microfluidic devices are bonded.

#### **Figure 12.**

*Optimization and validation: (a) experimental result, (b) simulation result with default settings, and (c) simulation results (after the cycle including the packing and cooling stage) with optimized parameters for the replication of flow cytometer structures; (d) experimental result, (e) simulation result with default settings, and (f) simulation results (after the injection stage) with optimized parameters for the replication of microfluidic droplet cylinders [55].*

**45**

**Figure 14.**

*The microfluidic chip bonding state with times [58].*

*Prototyping and Production of Polymeric Microfluidic Chip*

UV-curable adhesive as an intermediate layer has also been developed to assemble the disposable PMMA chips [57]. The substrate is firstly washed by ultrasonic cleaning equipment with deionized (DI) water and flushed with nitrogen before bonding. Then the adhesive is applied to the cover plate by spin coating (**Figure 13b**). After spin coating, the cover plate is assembled with the substrate, then silicone tubes are connected to the inlet and outlet ports of the chips. According to **Figure 13c**, the isopropanol is injected into the inlet ports and comes out from the outlet port through the silicone tubes in the flushing process. This process is aimed at flushing out the uncured adhesive that has been trapped inside the microchannels to prevent the channel clogging. In the last stage, the assembled chips are exposed to the UV light irradiation and the polymer chains in the adhesive system are crosslinked. **Figure 14** shows the bonding state of a microfluidic chip with time using adhesive

Although this method is useful for disposable devices, the storage time of adhesives at room temperature should be highlighted. Meanwhile, using isopropanol to flush out the uncured adhesive is a complicated procedure, as it might also wash out the adhesive at the edge of the microchannels, then the bonding effect will be reduced. In this way, the burst pressure should be conducted in case the edge of the

*Schematic diagram of the microchannel fabrication and bonding process: laser ablation for the fabrication of through holes on PMMA (a); spin coating of UV curable adhesive on cover plate (b); flushing out the un-crosslinked adhesives (c); UV exposure to induce the crosslinking of adhesives in the whole chip system [57].*

*DOI: http://dx.doi.org/10.5772/intechopen.96355*

bonding technology.

**Figure 13.**

channels is not fully bonded.

*Prototyping and Production of Polymeric Microfluidic Chip DOI: http://dx.doi.org/10.5772/intechopen.96355*

UV-curable adhesive as an intermediate layer has also been developed to assemble the disposable PMMA chips [57]. The substrate is firstly washed by ultrasonic cleaning equipment with deionized (DI) water and flushed with nitrogen before bonding. Then the adhesive is applied to the cover plate by spin coating (**Figure 13b**). After spin coating, the cover plate is assembled with the substrate, then silicone tubes are connected to the inlet and outlet ports of the chips. According to **Figure 13c**, the isopropanol is injected into the inlet ports and comes out from the outlet port through the silicone tubes in the flushing process. This process is aimed at flushing out the uncured adhesive that has been trapped inside the microchannels to prevent the channel clogging. In the last stage, the assembled chips are exposed to the UV light irradiation and the polymer chains in the adhesive system are crosslinked. **Figure 14** shows the bonding state of a microfluidic chip with time using adhesive bonding technology.

Although this method is useful for disposable devices, the storage time of adhesives at room temperature should be highlighted. Meanwhile, using isopropanol to flush out the uncured adhesive is a complicated procedure, as it might also wash out the adhesive at the edge of the microchannels, then the bonding effect will be reduced. In this way, the burst pressure should be conducted in case the edge of the channels is not fully bonded.

#### **Figure 13.**

*Advances in Microfluidics and Nanofluids*

Based on an experimental study on the filling behavior of microfluidic surface structures (**Figures 10(b)** and **11(a)**), the real responses of the injection molding machine are acquired and adopted in the process settings of the simulation with the help of process monitoring [55]. In addition, the effect of microscale sensitive parameters on the replication of surface structures using simulation is systematically studied and validated by flow front profile, cross-sectional profile, and replication of the structures. Consequently, the combination including a relatively higher heat transfer coefficient (30,000 W/(m2·K)) of the injection stage, standard atmospheric pressure (0.1 MPa) as the initial air pressure of venting, 0.7 as the friction coefficient for wall slip and a freezing temperature of 20 degrees above the glass transition temperature is selected. In terms of the flow cytometer surface structures, replication defects in experiments (circled in **Figure 12(a)**) are successfully predicted after the optimization as the blue parts shown in **Figure 12(c)**. Besides, the insufficient replication of the droplet cylinders (the areas in white in

**Figure 12(c)**) is also predicted after the selected parameters are applied.

[56], where the adhesive is cured and microfluidic devices are bonded.

*Optimization and validation: (a) experimental result, (b) simulation result with default settings, and (c) simulation results (after the cycle including the packing and cooling stage) with optimized parameters for the replication of flow cytometer structures; (d) experimental result, (e) simulation result with default settings, and (f) simulation results (after the injection stage) with optimized parameters for the replication of* 

The bonding methods for microfluidics comprises adhesive bonding, thermal fusion bonding, UV assisted thermal bonding, and solvent bonding. Following each section is introduced based on recent research findings with the mechanism, applicable materials, and process parameters of each bonding method. Finally, the challenges and relevant solutions for different bonding techniques are given.

Adhesive bonding is a simple manner to seal microfluidic devices, compared to other bonding techniques. By applying the liquid adhesive onto the surface of the chips, the solvent composition starts to evaporate till two parts are bonded. Besides, some adhesives with epoxy or acrylate compositions need to be cured under UV light irradiation or upon heating. After mixing with the photo-initiator or catalyzing agent, polymerization or crosslink reaction can occur in the adhesive system

**3.3 Bonding techniques for microfluidic devices**

*3.3.1 Adhesive bonding*

**44**

**Figure 12.**

*microfluidic droplet cylinders [55].*

*Schematic diagram of the microchannel fabrication and bonding process: laser ablation for the fabrication of through holes on PMMA (a); spin coating of UV curable adhesive on cover plate (b); flushing out the un-crosslinked adhesives (c); UV exposure to induce the crosslinking of adhesives in the whole chip system [57].*

**Figure 14.**

*The microfluidic chip bonding state with times [58].*

### *3.3.2 Thermal fusion bonding*

During the thermal fusion bonding process, the heating temperature is raised above the glass transition temperature (Tg) of the cover plate [19]. Meanwhile, a hold pressure is applied to enhance the mating contact forces between two surfaces. To achieve a strong bond, the heating temperature and the hold pressure should be high enough to ensure the complete diffusion of the polymer chains. In this case, the bond strength in the interface can be as high as the cohesive strength in the bulk material. According to **Figure 15**, the cover is first treated by O2 plasma to make its surface more hydrophilic. In this case, the adhesion between the COC cover plate and PMMA substrate is greatly improved. During the thermal press process, heat and constant pressure are provided. Steel platen transfers both heat and pressure to the chips. Two rubber sheets are used to distribute the pressure evenly and two polyimide films are used for the anti-sticking purpose (**Figure 15**).

One critical problem of thermal bonding is that the temperature and the pressure cannot be too high, otherwise, the microchannels may collapse and their integrity cannot be well maintained. Therefore, the heating temperature, hold pressure, and hold time should be controlled and adjusted to achieve high bond strength and limit the channel deformation. The balance should be achieved among the heating temperature, hold time, and hold pressure. These parameters should be well adjusted to maintain the integrity of the channels.

#### *3.3.3 UV assisted thermal bonding*

The channel collapse is hard to avoid during thermal bonding, as the heating temperature is often higher than the Tg of material. Therefore, it is important to lower the heating temperature. In this case, the substrate or cover plate can be pre-treated by UV/Ozone to achieve bonding at low temperature. The pretreated surface has higher energy due to oxidation. Therefore, the hydrophilicity and wettability are improved. As a result, the adhesion between the two surfaces is promoted.

Tsao et al. [60] compared the cross-section of the PMMA microchannels with and without UV/Ozone pre-treatment. As shown in **Figure 16(a)**, this chip treated by UV/Ozone had good bonding integrity. However, the untreated chips appeared obvious channel collapse as shown in **Figure 16(b)**. It is considered is because the treated chip had higher bond strength than the untreated chip (0.624 mJ/cm2 compared to 0.003 mJ/cm2 ).

**47**

*3.3.4 Solvent bonding*

**Figure 16.**

**Figure 17.**

*9.5 mm[h] [61].*

change during bonding.

**4. Conclusions**

Organic solvents can interact with polymer materials due to their similar solubility. Two polymer substrates are bonded together, which is called solvent bonding. This solubility can be determined by the Hildebrandt parameter (δ). Ogilvie et al. [61] used chloroform vapor to bond the PMMA substrates. Two PMMA substrates were first exposed to chloroform vapor for 4 minutes. In this stage, the solvent was only 2–3 mm below the surface of the chip and both chips and solvent were covered by a glass lid to form a vapor exposure chamber (**Figure 17**). Then two substrates were bonded at 65 °C for 20 minutes, followed by the cooling process to room temperature in 10 minutes. All chips needed 12 hours of post-conditioning before use. The optical properties were well maintained after bonding and high bond strength was achieved. Solvent vapor is more controllable than traditional vapor bonding techniques such as dipping or soaking in the solvent. However, controlling the solvent concentration is necessary especially for solvent mixtures, as it will

*Schematic of the bonding process. The PMMA chip shown has overall dimensions of 40[w] x 80[l] x* 

*SEM images of 500 mm wide, 180 mm deep PMMA microchannels: (a) thermal bonding of 24 min at 60°C, and (b) thermal bonding at 100°C [60]. Copyright (2007) with permission from Royal Society of Chemistry.*

In this chapter, the related manufacturing technologies for microfluidic chip fabrication are detailly described. Although rapid prototyping technologies for microfluidic chips, such as PDMS casting, micro machining, and 3D-printing, are well used in laboratory, the efficiency, machining accuracy and surface integrity of chips are still problematic for low-cost industrial batch production. Mass

*Prototyping and Production of Polymeric Microfluidic Chip*

*DOI: http://dx.doi.org/10.5772/intechopen.96355*

#### **Figure 15.**

*Schematic of the protocol used for assembly of the hybrid-based fluidic devices and the thermal press instrument [59]. Copyright (2015) with permission from Royal Society of Chemistry.*

#### **Figure 16.**

*Advances in Microfluidics and Nanofluids*

During the thermal fusion bonding process, the heating temperature is raised above the glass transition temperature (Tg) of the cover plate [19]. Meanwhile, a hold pressure is applied to enhance the mating contact forces between two surfaces. To achieve a strong bond, the heating temperature and the hold pressure should be high enough to ensure the complete diffusion of the polymer chains. In this case, the bond strength in the interface can be as high as the cohesive strength in the bulk material. According to **Figure 15**, the cover is first treated by O2 plasma to make its surface more hydrophilic. In this case, the adhesion between the COC cover plate and PMMA substrate is greatly improved. During the thermal press process, heat and constant pressure are provided. Steel platen transfers both heat and pressure to the chips. Two rubber sheets are used to distribute the pressure evenly and two polyimide films are used for the anti-sticking

One critical problem of thermal bonding is that the temperature and the pressure cannot be too high, otherwise, the microchannels may collapse and their integrity cannot be well maintained. Therefore, the heating temperature, hold pressure, and hold time should be controlled and adjusted to achieve high bond strength and limit the channel deformation. The balance should be achieved among the heating temperature, hold time, and hold pressure. These parameters should be well adjusted to

The channel collapse is hard to avoid during thermal bonding, as the heating temperature is often higher than the Tg of material. Therefore, it is important to lower the heating temperature. In this case, the substrate or cover plate can be pre-treated by UV/Ozone to achieve bonding at low temperature. The pretreated surface has higher energy due to oxidation. Therefore, the hydrophilicity and wettability are improved. As a result, the adhesion between the two surfaces

Tsao et al. [60] compared the cross-section of the PMMA microchannels with and without UV/Ozone pre-treatment. As shown in **Figure 16(a)**, this chip treated by UV/Ozone had good bonding integrity. However, the untreated chips appeared obvious channel collapse as shown in **Figure 16(b)**. It is considered is because the treated chip had higher bond strength than the untreated chip (0.624 mJ/cm2

*Schematic of the protocol used for assembly of the hybrid-based fluidic devices and the thermal press* 

*instrument [59]. Copyright (2015) with permission from Royal Society of Chemistry.*

*3.3.2 Thermal fusion bonding*

purpose (**Figure 15**).

is promoted.

compared to 0.003 mJ/cm2

).

maintain the integrity of the channels.

*3.3.3 UV assisted thermal bonding*

**46**

**Figure 15.**

*SEM images of 500 mm wide, 180 mm deep PMMA microchannels: (a) thermal bonding of 24 min at 60°C, and (b) thermal bonding at 100°C [60]. Copyright (2007) with permission from Royal Society of Chemistry.*

#### **Figure 17.**

*Schematic of the bonding process. The PMMA chip shown has overall dimensions of 40[w] x 80[l] x 9.5 mm[h] [61].*

#### *3.3.4 Solvent bonding*

Organic solvents can interact with polymer materials due to their similar solubility. Two polymer substrates are bonded together, which is called solvent bonding. This solubility can be determined by the Hildebrandt parameter (δ).

Ogilvie et al. [61] used chloroform vapor to bond the PMMA substrates. Two PMMA substrates were first exposed to chloroform vapor for 4 minutes. In this stage, the solvent was only 2–3 mm below the surface of the chip and both chips and solvent were covered by a glass lid to form a vapor exposure chamber (**Figure 17**). Then two substrates were bonded at 65 °C for 20 minutes, followed by the cooling process to room temperature in 10 minutes. All chips needed 12 hours of post-conditioning before use. The optical properties were well maintained after bonding and high bond strength was achieved. Solvent vapor is more controllable than traditional vapor bonding techniques such as dipping or soaking in the solvent. However, controlling the solvent concentration is necessary especially for solvent mixtures, as it will change during bonding.
