GB2131166A - DNA analyser - Google Patents

Abstract

A DNA analyser comprises an electrophoresis table (1), a position sensitive proportional radiation counter (2) mounted closely adjacent to the table for movement in a direction which is perpendicular to the direction of movement of a DNA sample (a) under electrophoresis, and a signal processor (14, 15, 16, 18, 19, 20, 22, 23, C) for processing a signal from the radiation counter to provide an indication of the position of the DNA sample on the table. <IMAGE>

Description

SPECIFICATION DNA analyser This invention relates to DNA analysers.

Autoradiography has been widely employed for detecting the gel-electrophoresis pattern of a plurality of activated DNA samples, an X-ray film being attached directly to a gel-electrophoresis plate and exposed. However, this method requires that electrophoresis should be interrupted during the detecting operation and this is extremely difficult. Therefore, it is possible only to detect electrophoresis patterns at certain points in time. Furthermore, this method has various other disadvantages such as long exposure time for detecting DNA samples with low-radioactivity, complicated operation, and it is difficult to automate.

Although the present invention is primarily directed to any novel integer or step, or combination of integers or steps, herein disclosed and/or as shown in the accompanying drawings, nevertheless, according to one particular aspect of the present invention to which, however, the invention is in no way restricted, there is provided a DNA analyser comprising: an electrophoresis table; a position sensitive proportional radiation counter mounted closely adjacent to the table for movement in a direction which is perpendicular to the direction of movement of a DNA sample under electrophoresis; and a signal processor for processing a signal from the radiation counter to provide an indication of the position of the DNA sample on the table.

In the preferred embodiment the radiation counter comprises an anode wire connected to a source of a relatively high voltage and a delay line arranged parallel to but spaced from the anode wire so that charge caused in the anode wire by radiation from the DNA sample induces a current pulse in the delay line for processing by the signal processor.

The signal processor may include a time-toamplitude converter for producing an analog signal which has a value related to the relative position of the current pulse induced in the delay line.

The signal processor may include computing means for receiving the output of the converter and producing data corresponding to the position of the current pulse induced in the delay line. Said computing means is preferably arranged to control motor means for moving said radiation counter and the speed of electrophoresis of the DNA sample.

The invention is illustrated, merely by way of example, in the accompanying drawings, in which: Figure 1 is a schematic side view of a DNA analyser according to the present invention; Figure 2 is a plan view of part of the DNA analyser of Figure 1; and Figure 3 is a view of part of the DNA analyser of Figure 1 to explain the operation thereof.

Referring to the drawings there is shown one embodiment of a DNA analyser according to the present invention. A gel-electrophoresis plate 1 has electrolyte S1, S2 at opposite ends thereof. A plurality of DNA samples transfer from the electrolyte Si over the plate 1 in the direction indicated by an arrow A. A power source E is connected between the electrolyte Si and the electrolyte S2 and is controlled by a microcomputer C. A position sensitive proportional radiation counter 2 is mounted closely adjacent the plate 1 and is moved parallel to the direction indicated by an arrow B by a motor M or other moving device. The direction indicated by the arrow B is perpendicular to the direction indicated by arrow A. The motor M is controlled by the microcomputer C and is guided on a rail R connected to a shaft of the motor.The radiation counter 2 comprises a shield 3 which has an opening facing the plate 1, and an anode wire 4 extending therethrough in a direction parallel to the direction indicated by arrow A. The anode wire 4 is electrically insulated from the shield 3. A delay line 5 is provided adjacent and parallel to the anode wire 4. An inlet valve 6 enables a charge or ionisable gas such as argon etc. to enter the shield 3 and an outlet valve 7 allows the gas to leave the shield. The anode wire 4 is connected to a high voltage power source 9 through a terminal 8 mounted on the shield 3. The delay line 5 is connected to terminals 10, 11 mounted on the shield and signals on the delay line 5 are taken from the terminals 10, 11 on lines 12, 13 respectively.The line 12 is connected to a start input terminal 17 of a time-to-amplitude converter 16 through an amplifier 14 and a discriminator 15, and the line 13 is applied to a stop input terminal 21 of the converter 16 through an amplifier 18, a discriminator 19 and a delay circuit 20. The output of the converter 16 is connected by a line 24 to a multi-channel analyser 22 which is connected to a memory 23 and the microcomputer C which controls the power source E and the motor M. The amplifiers 14, 18, the discriminators 15, 19, the delay circuit 20, the converter 16, the analyser 22, the microcomputer C and the memory 23 form a signal processing circuit for processing the signals on the lines 12, 13.

The operation of the DNA analyser is as follows.

Referring to Figure 3, radioactive rays emanating from an activated DNA sample a ionises the gas in the shield 3 causing the emission of electrons. Since a positive potential is applied to the anode wire 4 by the high voltage power source 9, the electrons move to the anode wire while producing secondary electrons. A current pulse is thus produced at a position b on the anode wire 4 corresponding to the position of the DNA sample a on the plate 1. This pulse induces a pulse at a position con the delay line as a result of mutual electromagnetic interaction. This current pulse advances on the delay line 5 in both a direction x and a direction y, and corresponding signals appear on lines 12, 13. The distance D between the plate 1 and the anode wire 4 is approximately 1 mm.The signal on the line 12 is amplified by the amplifier 14, discriminated into a noise component and a signal component by the discriminator 15 and the signal component is passed to the start input terminal 17 of the converter 16. The signal on the line 13 is amplified by the amplifier 18, and discriminated into a signal component and a noise component by the discriminator 19. Then, the signal component is passed to the stop input terminal 21 of the converter 16 through the delay circuit 20 where it is delayed by a predetermined delay time T. The delay time T provided by the delay circuit 20 is equal to the delay time of the delay line 5. The converter 16 converts the period of time from the signal being applied to the start input terminal 17 of the converter to the signal being applied to the stop input terminal 21 into an electrical analog signal which appears on the line 24.Since the transmission speed of the current pulse on the delay line is constant, the analog signal has a value related to the position of the current pulse induced on the delay line. The analog signal on the line 24 from the converter 16 is applied to the analyser 22 and, after being stored in a channel corresponding to its value for a certain period, it is transmitted to the microcomputer C. The microcomputer C carries out calibration and background correction operations on the transmitted data, puts the resulting positional data into the memory 23 and resets the analyser to initialise it. Then the microcomputer C supplies a signal to the motor M so as to move the counter 2 in the direction of the arrow B by a predetermined distance readyforthe next measurement.

The above operation is repeated automatically so that the parallel electrophoresis patterns of several DNA samples on the plate 1 are detected and positional data for all of them is stored in the memory 23. In the case where the measurement requires a relatively long time on account of low radioactivity of the DNA samples, a signal is supplied to the microcomputer C to the power source E to decrease the electrophoresis voltage thereby to decrease the electrophoresis speed so that the time relationship of the patterns of the DNA samples may be maintained.

Further, in the case where the plate 1 is too long for the counter 2 or for measuring an electrophoresis pattern which changes relatively quickly, the above operation can be repeated after a predetermined time.

The DNA analyser described above enables the pattern of radioactivity of DNA samples on an electrophoresis board to be automatically detected in a short period and also changing electrophoresis patterns of DNA samples to be measured. Further, it has the advantage that the electrophoresis patterns of a plurality of DNA samples on the plate 1 can be measured almost simultaneously with a single radiation counter 2.

Claims (8)

1. A DNA analyser comprising: an electrophoresis table; a position sensitive proportional radiation counter mounted closely adjacent to the table for movement in a direction which is perpendicular to the direction of movement of a DNA sample under electrophoresis; and a signal processor for processing a signal from the radiation counter to provide an indication of the position of the DNA sample on the table.

2. A DNA analyser as claimed in claim 1 in which the radiation counter comprises an anode wire connected to a source of a relatively high voltage and a delay line arranged parallel to but spaced from the anode wire so that charge caused in the anode wire by radition from the DNA sample induces a current pulse in the delay line for processing by the signal processor.

3. A DNA analyser as claimed in claim 2 in which the signal processor includes a time-to-amplitude converter for producing an analog signal which has a value related to the relative position of the current pulse induced in the delay line.

4. A DNA analyser as claimed in claim 3 in which the signal processor includes computing means for receiving the output of the converter and producing data corresponding to the position of the current pulse induced in the delay line.

5. A DNA analyser as claimed in claim 4 in which said computing means is arranged to control motor means for moving said radiation counter and the speed of electrophoresis of the DNA sample.

6. A DNA analyser substantially as herein described with reference to and as shown in the accompanying drawings.

7. A DNA analyser characterised in that said analyser comprises a gel-electrophoresis device, a position sensitive proportional counter (hereinafter referred to as PSPC) which is closely mounted on an electrophoresis board of said gel-electrophoresis device, a moving device for driving the PSPC in the right angle direction to the moving direction of a DNA sample which moves on said electrophoresis board, and a signal processor for processing the signal obtained from said PSPC, and the radioactive rays from a plurality of DNA samples moving in parallel on the electrophoresis board is detected.

8. Any novel integer or step, or combination of integers or steps, hereinbefore described, irrespective of whether the present claim is within the scope of, or relates to the same or a different invention from that of, the preceding claims.