Frequency-shift cmos magnetic biosensor array with single bead sensitivity and no external magnet

A method for detecting one or more magnetic particles, comprising the steps of:

• (a) providing an integrated measurement system having a plurality of N sensor cells, where N is an integer greater than 1, each of said sensor cells being represented by an integer in the range of 1 to N, each of said sensor cells including an active sensor oscillator configured to have an active sensor oscillator frequency and a reference oscillator configured to have a reference sensor oscillator frequency, a difference between said active sensor oscillator frequency and said reference sensor oscillator frequency being representative of a presence or an absence of one or more magnetic particles within a sensor volume of said sensor cell;
• (b) selecting an integer in the range of 1 to N;
• for said selected integer,
• (b1) measuring a selected one of said active sensor oscillator frequency and said reference sensor oscillator frequency of said sensor cell;
• (b2) waiting for a first delay time;
• and
• (b3) measuring after said first delay time the other of said active sensor oscillator frequency and said reference sensor oscillator frequency for said sensor cell;
• (c) recording a start time for said measurement according to step (b1);
• (d) selecting a different integer in said range of 1 to N, and repeating steps (b1) through (b3) for said integer;
• (e) repeating step (d) until all of the integers in the range 1 to N have been employed one time;
• (f) determining whether a period substantially equivalent to a time constant of a flicker process has elapsed since the recording of said start time in step (c);
• (g) if a period substantially equivalent to a time constant of a flicker process has elapsed since the recording of said start time in step (c), repeating steps (b) though (f) a desired number of times, and if a period substantially equivalent to a time constant of a flicker process has not elapsed since the recording of said start time in step (c), performing step (h);
• (h) waiting until a period substantially equivalent to a time constant of a flicker process has elapsed since the recording of said start time in step (c), and then repeating steps (b) though (f) a desired number of times;
• (i) upon completing said steps (b) through (h) said desired number of times, computing for each sensor cell a presence or absence of one or more magnetic particles;
• and
• (j) recording a result for each sensor cell indicative of said presence or absence of one or more magnetic particles.

An integrated magnetic particle measurement system array for detecting a presence or absence of magnetic particles in a sample volume, comprising:

• a substrate having a surface;
• two or more sensor cells, each of said sensor cells comprising a differential sensor pair including an active sensor oscillator configured to have an active sensor oscillator frequency, said active sensor oscillator frequency responsive to one or more magnetic particles situated within a sample volume and a reference oscillator configured to have a reference sensor oscillator frequency, said two or more sensor cells configured to be operative in the absence of an externally applied magnetic field;
• a down shift circuit electrically coupled via a multiplexer to said active sensor oscillator and said reference sensor oscillator of each sensor cell and having a down shift circuit output, said down shift circuit configured to down shift in a time multiplexed manner from each of said sensor cells said active sensor oscillator frequency to a downshifted active sensor oscillator frequency and said reference sensor oscillator frequency to a downshifted reference sensor oscillator frequency;
• and
• a counter communicatively coupled to said down shift circuit output and configured to output at a count output terminal from each of said sensor cells in said time multiplexed manner, a first count representative of said active sensor oscillator frequency and a second count representative of said reference sensor oscillator frequency, and wherein a calculated difference between said first count and said second count indicates a presence or an absence of one or more magnetic particles within said sample volume of said active sensor oscillator of each sensor cell.