Biomedical Engineering Reference
In-Depth Information
Currently, proteomics in clinical (not POC) settings utilize fluorescent detection
based on the ELISA, which report detection limits on the order of 1 pM with 2
orders of linear dynamic range. The wash-free assay presented here has a similar
dynamic range but achieves over an order of magnitude higher sensitivity in a
fraction of the time. The higher sensitivity is primarily attributable to using MNP
tags rather than fluorescent labeling. With the magnetic nanotechnology described
in this chapter, detection down to 50 fM in a 25L sample has been demonstrated
[
17
]. While the sensitivity needs for POC settings is generally less stringent, having
higher sensitivity allows for a shorter assay time, leading to faster diagnostic times.
The higher sensitivity of this technology may also facilitate the earlier diagnosis of
disease.
The MNP tags require an external magnetic field to induce a magnetic moment,
and the sensors require the magnetic field to modulate the sensor response to a
higher frequency. The optimal magnetic field for this particular combination of
sensor and MNP has been shown previously to be 25 Oe [
18
]. Because the optimum
is fairly shallow, this allows the field to be reduced without a significant loss in
sensitivity. At a magnetic field of 15 Oe (60 % of the optimum), the signal per
MNP decreases by only 20 %. With this small reduction in sensitivity, the power
consumption can be significantly reduced.
GMR spin-valves typically exhibit high flicker noise (also known as 1/F noise
because it is inversely proportional to frequency). To increase the signal-to-noise
ratio (SNR) and improve the detection capability of the device, the signal from the
MNP tags is modulated away from the low-frequency noise to a higher frequency
[
19
]. To recover this signal, the microprocessor digitizes the response from the
GMR nanosensors and performs the filtering and demodulation. Figure
7.13
c, d
illustrates this process with the incoming modulated signal and the clean output
signal after a 113th order digital filter has been applied. A minimalistic version of the
computationally intensive signal processing algorithms used in our desktop station
was implemented due to the limited computational power of the microprocessor
[
20
]. With the integration of a power source, signal processing, and display
functionality into the handheld detection module, no additional components are
required to run and measure an assay, allowing it to truly be a POC testing device.
A fundamental element of the handheld device is a microchip microprocessor
(dsPIC30F6012a) which runs at 80 MHz (20 MIPS). The microprocessor has an
integrated 12-bit analog to digital converter used to digitize the signals from
the sensors. Furthermore, the microprocessor communicates to the direct digital
synthesizer chips via an integrated SPI bus. However, the primary reason for
choosing a high-end microprocessor is for the heavy DSP algorithms that it
performs. To extract the single tone from the spectrum with the double modulation
scheme, the 113 tap digital FIR bandpass filter is applied to the incoming samples.
The tap count was chosen after all of the code had been written such that it filled the
remaining memory of the microprocessor to minimize the noise bandwidth of the
extracted tone. The root mean square value of the filter output is proportional to the
magnetoresistance of the sensor and is saved to an internal buffer. The sensors are
scanned in a round robin fashion, rotating from sensor 1 through sensor 8. For each
