## 4 Applications in Clinical Assays
### Detection of Infectious Diseases Caused by Viruses  
MIPs/SIPs based biosensors have wide applications for the detection of virus in medical diagnostics. [PERSON] and coworkers [62] summarized the state-of-the-art application of MIPs for virus detection.  
Figure 6: Schematic preparation procedures for three types of direct micro-contact imprinting (**A**) and indirect micro-contact imprinting (**B**). Reproduced from [26]—Published by Elsevier B.V.  
The detection performance for influenza, Dengue virus, Japanese encephalitis virus (JEV), human immunodeficiency virus (HIV), hepatitis A virus, hepatitis B virus, adenovirus, and picornaviruses were discussed. However, the studies cited in their review paper mainly used quartz crystal microbalance (QCM), surface plasmon resonance (SPR), fluorescence resonance energy transfer (FRET), and resonance light scattering (RLS) as transducers. In this section, the MIPs/SIPs based electrochemical biosensors for virus detection are emphasized.  
Human papillomavirus (HPV) is a group of more than 200 related viruses, some of which are spread through anal or vaginal sex. Long-lasting or chronic infections caused by HPV can induce cancer. [PERSON] and coworkers [63] presented a MIPs based nano-sensor to detect human papillomavirus derived E7 protein. Analysis of EIS data revealed that the detection of E7 protein can be as low as sub pg L-1 levels. Notably, the human papillomavirus E6 protein (type-16) was not recognized by the E7 imprinted polymers. It shows outstanding specificity.  
As a member of the Flaviviridae virus family, Zika virus usually infects human beings and typically causes a skin rash, conjunctivitis, red eyes, malaise, muscle and joint pain, headache, or mild fever. Recently, [PERSON] et al. [52] developed an electrochemical sensor based on SIPs and graphene oxide composite for Zika virus detection. The sensor was applied to detect virus in both PBS solutions and serum. In the PBS solution, LOD was found to be \(2\times 10^{-2}\) PFU/mL in the presence of the dengue virus. For serum samples, dilution steps were added to reduce the background signal. The LOD found to be \(2\times 10^{-3}\) in 10% serum samples and \(5\times 10^{-2}\) PFU/mL (10-250 RNA copies/mL) in 1% serum samples. Generally, the lowest LOD in real samples should be 6000 (\(\sim\)10\({}^{4}\)) particles (or \(\sim\)10\({}^{-3}\) PFU) per mL. This performance is sufficient for Zika virus detection in practical applications.  
Acquired immune deficiency syndrome (AIDS) is a severe infectious disease caused by HIV. HIV is a member of retroviruses, it is disseminated mainly by contaminated blood transfusions, unprotected sex, and others. [PERSON] et al. [64] developed an electrochemical biosensor based on multi-walled carbon nanotubes modified MIPs for the detection of HIV-p24. They proved that MIPs have a specific recognition capacity for HIV-p24. The linear range was found to be from \(1.0\times 10^{-4}\) ng cm\({}^{-3}\) to 2.0 ng/cm\({}^{-3}\). The LOD was tested to be 0.083 pg/cm\({}^{3}\). The reported biosensor showed excellent selectivity and stability. It was successfully used for the detection of HIV-p24 in a human serum sample.