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An alternative, though similar approach to that described in Example 2.5 is the use of immobilized metal af nity chromatography (IMAC) which takes advantage of metals immobilized on an af nity matrix. A fusion of the gene coding for the protein to be puri ed (white) with a sequence of six histidine residues (grey) called a his-tag is constructed which contains an enterokinase cleavage site (hatched) as shown in the illustration. This fusion is expressed in an E. coli expression system. The LO signal modulates the transconductance, and therefore the gain of the common-source ampli er for the IN signal, from zero below pinch off to the maximum value along the load line. The behaviour is very much like that of a switch with gain. In Figure 7.7, the load line has a constant Vds voltage path, implying a short-circuit drain termination at the LO fundamental frequency and harmonics; this is discussed in some detail below, together with the terminations at the IN and OUT frequencies. This con guration does not provide any intrinsic isolation between LO and IN signals and has a very bad isolation between LO and OUT ports since the already large LO signal is further ampli ed by the FET into the OUT port. The IN signal is also ampli ed by the FET, but its amplitude is relatively smaller and is more easily ltered out at the OUT port. The LO and IN ports are isolated from the OUT signal because of the low reverse gain of the FET. This con guration is likely to provide a conversion gain if properly terminated; however, it is also prone to instability if the gain is exceedingly large. The load line 2 in Figure 7.7 corresponds to a drain mixer, where the main nonlinearities are the transconductance and the output conductance, modulated by an LO signal applied to the drain, with the gate voltage fairly constant. The input signal is applied to the gate, while the output signal is taken at the drain port, as shown in Figure 7.9. The LO signal modulates the transconductance and the output conductance of the FET, and therefore the gain of the common-source ampli er for the IN signal, while switching between the saturated and ohmic regions of the characteristics. The behaviour is again like that of a switch with gain. In Figure 7.7, the load line has a constant Vgs voltage path, implying a short-circuit gate termination at the LO fundamental frequency and harmonics. This con guration does not provide any intrinsic isolation between LO and OUT signals and has a bad isolation between IN and both OUT and LO ports since the IN signal is ampli ed by the FET. The IN port is isolated from the LO and OUT signals because of the low reverse gain of the FET. It is likely to provide a conversion gain if properly terminated; however, it is also prone to instability if the gain is large. s , = exp(-PknA),
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