## 3 Applications of Single Molecule Measurement: Disease Diagnosis, Monitoring
### Cancer Diagnosis  
One of the most widely reported studies is cancer diagnosis. It is generally known that cancer is caused by genetic abnormalities in cells, but there are many possible causes, and the corresponding diagnostic markers are different for each of the causes. In the application of cancer diagnosis for personal medical care, it is necessary to find the cause of each cancer individually and to administer the corresponding drug appropriately. Therefore, the simultaneous detection of various diagnostic marker molecules is required.  
Diagnostic marker molecules for cancer diagnosis include specific DNA gene sequences, specific genomic sequence duplications such as specific short tandem repeats (STRs), overexpression or suppression of miRNAs, CpG methylation, and tumor marker proteins and so on.  
Sequencing methods by nanodevices are utilized for the detection of cancer related gene sequences such as genetic mutations and polymorphisms [63; 64; 65; 66; 67]. For example, the genetic abnormality of TP53, a specific oncogene, was detected in blood samples [67]. It is possible to perform the detection by the Illumina and Sanger sequencing method but the nanodevice based single-molecule sequencer can detect them cheaper and faster.  
Indirect detection methods are utilized for the detection of cancer markers by using nucleotide probes, which are designed to selectively bind to the target cancer marker. For instance, by using a nucleic acid probe with complementary base pairs and a target miRNA, the detection of cancer-related miRNAs was successfully achieved [68; 69; 70; 71; 72; 73; 74; 75]. In this method, a specific miRNA is detected by the probe molecule bound to the miRNA conjugates in blood. In addition, by using multi targeting probes, which can be hybridized with several types of miRNAs, multiple target miRNAs were detected simultaneously [70; 71]. For no nucleotide type target markers, detection by using the nucleotide probe, which can interact with target markers, was successfully achieved [79; 81]. For instance, using a nucleic acid aptamer probe, prostate-specific antigen (PSA) was detected [79]. The development of the evolutionary engineering method using nucleic acids and peptides can produce probe molecules with high selectivity so that the nanodevice detection method using probe molecules can become more accurate in the future. CpG methylation has been reported in various cancers such as colorectal cancer and lung cancer, and has attracted attention  
\begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Detection** & **Target Marker** & **Detection Method** & **Detection Device** & **Sample Source** & **Reference** \\ \hline Bacterial lower respiratory infections (LRIs) & MecA blaTEM, sul1 and dfrA17,gene, E.coil, MRSA & Sequencing (metagenome) & bionanopore (MiniION) & respiratory samples from patients & [107] \\ \hline Polyglutamine diseases (e.g., spinal and bulbar muscular drug), OGGGCC and iCCTG disease) & Tandem repeat regions (CAG, CAA, GöGGCC and iCCTG) & Sequencing (Tandem genotyping) & bionanopore (MiniION) & - & [108] \\ \hline Rare Mendelian disorders & Structural variants of genes DNA & Sequencing & bionanopore (Minion) & - & [109] \\ \hline Lassa fever (Lassa virus) & Lassa virus & Sequencing & bionanopore (Minion) & & [110] \\ \hline Volatile organic compounds (VCCs) & Acetone & capacitance signal characterization & nanogap & - & [111] \\ \hline TNT & Nitroaromatics & Binding & bionanopore (bio engineered nanopore) & TNT & [112] \\ \hline \hline \end{tabular}
\end{table}
Table 2: _Cont._as target cancer markers. By using single-molecule detection with nanodevices, such epi-genetic detection was also reported [83].