**4.2 Permselective glucose sensing with red cell membrane-coated biosensors**

In biosensors, not only sensitivity but also specificity (selectivity) is important because numerous molecules coexist in the biological samples that may interfere the detection [35]. For example, blood contains ions, saccharides, proteins, and blood cells which hinder accurate glucose detection. Enzymatic glucose biosensors, most widely used, employ glucose oxidase or glucose dehydrogenase

**Figure 7.**

*Biodistribution of RCM-coated gold nanoparticles in mice [7]. The fluorescently labeled nanoparticles were injected intravenously into the mice. The fluorescent intensity at the liver, kidney, spleen, brain, lung, heart, and blood was measured at 24, 48, and 72 h. (A) fluorescent intensity per gram of tissue (n = 6). (B) Relative signal per organ.*

#### **Figure 8.**

*Schematic illustration of RCM-coated glucose sensor [9]. The RCM-coated enzymatic glucose sensor specifically reacts with glucose via taking advantage of glucose transporter-1 (GLUT1).*

**145**

molecules (**Figure 9**) [9].

**5. Conclusions**

**Figure 9.**

**Acknowledgements**

*Application of Red Cell Membrane in Nanobiotechnology DOI: http://dx.doi.org/10.5772/intechopen.84274*

for selective detection of glucose. However, the enzymes react with glucose and other similar structured molecules (mono- and disaccharides) such as fructose, galactose, and maltose in blood. For this reason, glucose sensors are interfered by the molecules. It is reported that RCM which has glucose transporter was employed as glucose-selective permeable membrane by taking advantage of GLUT (**Figure 8**) [9]. The RCM-coated sensor showed high selectivity to glucose compared to uncoated sensor. In detail, the uncoated sensors are highly affected by the increment of interfering molecules (e.g., ascorbic acid, uric acid, and galactose), whereas the RCM-coated sensors exhibit consistency in glucose detection. In particular, RCM-coated sensor showed that the signals of glucose with interfering molecules barely change from that of glucose without interfering

*Selectivity test of RCM-coated glucose sensors under competitive interactions between glucose and each interfering molecule [9]. The selectivity test was conducted with 5 mM of glucose blended with each interfering molecule, e.g. (A) ascorbic acid (AA), (B) uric acid (UA), or (C) galactose (GA). The black and red bars* 

*represent the output signal of uncoated sensor and RCM-coated sensor, respectively.*

The RCM has various types of membrane proteins such as membrane receptor, transporter, and cell adhesion molecules. Each type of membrane proteins is full in potentials to be applied in various fields such as drug delivery system and biosensor. The well-evolved functionality of membrane proteins can be easily utilized by coating the RCM on nanomaterial and solid surface of sensors. Currently, drug delivery system is the major field of RCM application because the membrane can confer the immune evasive properties of RCM to the nanomaterials. In the future, it is expected that the RCM will be increasingly applied in development of highly

This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MSIP) (No. NRF-2016R1A2B4010269, NRF-2017R1A6A3A11034311 and NRF-2018M3C1B7020722). This material is also supported by the Ministry of Trade, Industry and Energy (MOTIE, Korea) under Industrial Technology Innovation Program (No.10079316). Gyudo Lee is thankful

selective biosensors utilizing various transporters on RCM.

for the financial support by Korea University Grant.

*Application of Red Cell Membrane in Nanobiotechnology DOI: http://dx.doi.org/10.5772/intechopen.84274*

#### **Figure 9.**

*Erythrocyte*

**Figure 7.**

*signal per organ.*

which were abundant and diverse on RCM. In this regard, the immune evasive properties of RCM-functionalized nanomaterials have great potential as clinical drug delivery carriers. In particular, it is researched that the RCM-functionalized nanoparticles showed good dispersion stability in serum and great biodistribution in mice model up to 72 h (**Figure 7**) [7]. Indeed, it is demonstrated that the RCM inhibits macrophage uptake. RCM-coated gold nanoparticles showed ~4 times

**4.2 Permselective glucose sensing with red cell membrane-coated biosensors**

In biosensors, not only sensitivity but also specificity (selectivity) is important because numerous molecules coexist in the biological samples that may interfere the detection [35]. For example, blood contains ions, saccharides, proteins, and blood cells which hinder accurate glucose detection. Enzymatic glucose biosensors, most widely used, employ glucose oxidase or glucose dehydrogenase

*Biodistribution of RCM-coated gold nanoparticles in mice [7]. The fluorescently labeled nanoparticles were injected intravenously into the mice. The fluorescent intensity at the liver, kidney, spleen, brain, lung, heart, and blood was measured at 24, 48, and 72 h. (A) fluorescent intensity per gram of tissue (n = 6). (B) Relative* 

*Schematic illustration of RCM-coated glucose sensor [9]. The RCM-coated enzymatic glucose sensor specifically* 

*reacts with glucose via taking advantage of glucose transporter-1 (GLUT1).*

higher immune evasive properties than bare gold nanoparticles [8].

**144**

**Figure 8.**

*Selectivity test of RCM-coated glucose sensors under competitive interactions between glucose and each interfering molecule [9]. The selectivity test was conducted with 5 mM of glucose blended with each interfering molecule, e.g. (A) ascorbic acid (AA), (B) uric acid (UA), or (C) galactose (GA). The black and red bars represent the output signal of uncoated sensor and RCM-coated sensor, respectively.*

for selective detection of glucose. However, the enzymes react with glucose and other similar structured molecules (mono- and disaccharides) such as fructose, galactose, and maltose in blood. For this reason, glucose sensors are interfered by the molecules. It is reported that RCM which has glucose transporter was employed as glucose-selective permeable membrane by taking advantage of GLUT (**Figure 8**) [9]. The RCM-coated sensor showed high selectivity to glucose compared to uncoated sensor. In detail, the uncoated sensors are highly affected by the increment of interfering molecules (e.g., ascorbic acid, uric acid, and galactose), whereas the RCM-coated sensors exhibit consistency in glucose detection. In particular, RCM-coated sensor showed that the signals of glucose with interfering molecules barely change from that of glucose without interfering molecules (**Figure 9**) [9].

#### **5. Conclusions**

The RCM has various types of membrane proteins such as membrane receptor, transporter, and cell adhesion molecules. Each type of membrane proteins is full in potentials to be applied in various fields such as drug delivery system and biosensor. The well-evolved functionality of membrane proteins can be easily utilized by coating the RCM on nanomaterial and solid surface of sensors. Currently, drug delivery system is the major field of RCM application because the membrane can confer the immune evasive properties of RCM to the nanomaterials. In the future, it is expected that the RCM will be increasingly applied in development of highly selective biosensors utilizing various transporters on RCM.

#### **Acknowledgements**

This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MSIP) (No. NRF-2016R1A2B4010269, NRF-2017R1A6A3A11034311 and NRF-2018M3C1B7020722). This material is also supported by the Ministry of Trade, Industry and Energy (MOTIE, Korea) under Industrial Technology Innovation Program (No.10079316). Gyudo Lee is thankful for the financial support by Korea University Grant.

*Erythrocyte*
