Differences

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--- oxfordapr202009a:start [2015/02/03 18:42] – magiero
+++ oxfordapr202009a:start [2015/02/05 04:24] (current) – magiero
@@ Line 32: / Line 32: @@
 ==== - Apparatus ====
 • [0049] The wells are divided into groups.  The picture uses 4 wells per group as an example.  One detection channel per group is used.  For some applications the sensor device might comprise a total of 4096 wells 21 and 1024 detection channels 30.\\
+• [0050] The apparatus includes a **switch arrangement** 31 which is capable of selectively connecting the detection channel to any one of the wells in the group.  In particular the switch arrangement is a **1-to-4 multiplexor** comprising 4 switches each connected to one well electrode 22 and a common contact 33 which is itself connected to the input of the detection channel 30.\\
+• [0051] The switches 32 are preferably semiconductor switches, preferably **field effect transistors**.  The switches are selected to provide **minimal leakage** to the detection channel either from the wells that are not connected through the switches that are open or from the **latch** 34 through the switches.  **Dynamic charge injection** effects are avoided by running the apparatus 1 with the switches in a static configuration for most of the time.\\
+• [0052] Any one single switch 32 is closed at a time.\\
+• [0053] There is no requirement to be able to change the configuration of the switch arrangement 31 rapidly.  Typically, **changes may be required on a time-scale of minutes** and a complete update should be achievable on a timescale of up to 0.1 s to l s.\\
+• [0059] The detection channel 30 includes a **charge amplifier** 40 that is a differential amplifier.\\
+• [0061] The output of the charge amplifier 40 is connected to two **sample-hold amplifiers** 44 arranged in parallel and optionally provided with voltage gain.  The S/H amps are used to provide **correlated double sampling**.  Each S/H is switched synchronously with the control switch 43.  The S/H output goes to a multiplexor 45 which supplies the date to a processing unit (assuming A/D conversion is done somewhere in between).\\
+• [0062] **Alternatively** can use two charge amplifiers 40 in parallel.\\
+==== - Sensor Selection Process [0068] - [0072] ====
+• Measure signals to choose some well in each group.  Facility to try again if no sensor found or if a once good sensor loses quality.\\
+• [0072] However, it is noted that the quality of performance of wells 21 becoming unacceptable is relatively rare.\\
+==== - Redundancy and Efficiency [0073] - [0090] ====
+• [0074] The insertion of membrane proteins into a lipid bilayer 26 is a random process that follows Poisson statistics. This means that even when the average number of membrane proteins per well 21 is one, a significant number of wells 21 may have none, two or more membrane proteins inserted, and these wells 21 are then not useful. For example, it is found that in a particular embodiment the maximum probability for finding just one membrane protein in a well 21 is about 36%, and this is only achieved if conditions are optimal.  A greater or lesser membrane protein concentration quickly results in a reduction of useable wells 21 (especially a lesser exposure). **Current estimates for efficiency which is likely to be achieved in practical embodiments are about 20%**.\\
+• [0076] **Lipid bilayers 26 are formed with an efficiency which may be assumed to approach 100%** for current purposes. Membrane proteins are then inserted using a solution whose concentration and exposure time is adjusted to give a mean number of membrane proteins per well 21 near to one. Because the wells 21 might not in practice have a lipid bilayer 26 of the same size, their capture efficiencies will vary. This combines with Poisson statistics to give a spread in the number of membrane proteins per well 21. The apparatus 1 characterises the sensor device 2 to detect which wells 21 have active, useful membrane proteins.\\
+• [0078] The mean of the pore Poisson distribution depends on
+  - area of the lipid bilayer
+  - concentration of membrane proteins in the solution
+  - time for which lipid bilayer is exposed to the membrane protein solution
+• [0087] **Cross-bar switch** is possible, but much more complex.
+==== - Modified Detection Circuit [0091] - [0098] ====
+{{ detector3.png?400}}
+• [0092] In this one you can unblock the pores (supply an inverted potential) without affecting other wells 21.\\
+• [0095] Now provide a second switch arrangement 48 that can connect up the unblocking bias source 47 to the pore in question.\\
+• These switches are referenced in [[oxfordapr202009b:start | Dec. 01, 2009 patent]].