An example will help us understand this phenomenon: imagine a big room with a door; the maximum allowable value of the entering people in unit time is N. When the number

of people who need to enter the room in unit time check details is lower than N, the value of the entering people in unit time will increase with the increasing number of people who need to enter. When the number of people who need to enter the room in unit time is larger than N, the actual value of the entering people will equal to or even be lesser than N (especially for disordered conditions). Similarly, when IgG concentration is higher than the threshold value, the number of passing molecules will remain or decrease. The physical place-holding effect is weakened, which can result in the increase of ionic current. Single-biomolecule sensing Only an overall decline in the background current can be observed using PC membranes. In order to find the changes in the background current curve induced by a AG-881 in vivo single biomolecule’s translocation, the Si3N4 micropore is employed, and it is covered by the PC membrane containing nanopore arrays, which will significantly decrease the effective nanopore numbers. The effective areas of the two Si3N4 micropores used in our work are 1.77 μm2 (chip 1) and 3.14 μm2 (chip 2), which can TGF-beta/Smad inhibitor decrease the effective nanopore number from 106 and 107 to 10 and 19, respectively. They are integrated into the nanofluidic device for DNA sensing,

and the ionic current was recorded by patch clamp. In these cases, the probabilities of the simultaneous translocation events decreased N-acetylglucosamine-1-phosphate transferase dramatically. So, it is possible to obtain discrete ionic drops or blockades in the detected ionic curves during biomolecules’ translocations, which can provide more information for the translocation. Figure 6 shows the characteristic I-V curves obtained using chip 1 and chip 2, respectively. The theoretical amounts of the effective nanopores in chip 1 and chip 2 are 10 and 19, respectively. The results indicate that chip 2 processes bigger ionic conductance compared with chip 1. Obviously, more effective

nanopores correspond to more permeated areas, which can allow more ion translocations and result in bigger ionic currents, supposing that other conditions (such as concentration of electrolyte solution, applied voltage, pH value, and temperature) are not changed. For one integrated chip, higher concentration of KCl solution results in bigger ionic current if the other conditions are not changed, as shown in Figure 7. This is due to the increase of ion in the unit solution volume. Figure 6 The characteristic I- V curves for the integrated micro- nano pore in 0.75 mol/L KCl solution. The sizes of the Si3N4 pores are 1.5 and 2.0 μm. Figure 7 The characteristic I- V curves for the integrated micro- nano pore in different KCl solutions. The size of the Si3N4pore is 2.0 μm; the KCl solutions are from 0.