Biomedical Engineering Reference
In-Depth Information
sensor, the signal is acquired for 200 ms and the subsequent analysis takes 800 ms.
While the signal processing could be overlapped with the data acquisition or applied
in real-time, the tasks are undertaken sequentially to simplify the timing between
the acquisition and the processing steps. This signal acquisition and processing is
repeated throughout the duration of the test.
In POC settings, it is not practical to perform sample preparation prior to running
the diagnostic test. Accordingly, the platform must have reproducible detection
despite differences in the sample fluid (buccal swab, serum, urine, cell lysates, etc.),
pH, and temperature. Fortunately, GMR spin-valve sensors have been reported to be
insensitive to different sample matrices, rendering the platform highly generalizable
to a diversity of biologically relevant samples and removing the need for any
complex sample preparation [
21
]. This subtle requirement is often overlooked or
ignored when discussing POC diagnostics, but in fact is critical to the utility of such
a diagnostic device in real-world settings.
7.6
POC Detection Results via GMR Biosensor Arrays
The user interface of the detection module has been designed to provide both a
rapid readout and a user-friendly, easy-to-comprehend display. The microprocessor
monitors the real-time binding events and predicts the saturation signal based on the
initial binding trajectory. Monitoring the binding trajectory in real-time significantly
reduces the assay time and produces a more reliable final readout than taking a
single-point measurement at an arbitrary time prior to signal saturation. Figure
7.14
a
shows the binding curves of various concentrations of human immunodeficiency
virus (HIV) p24 protein ranging from 100 ng/mL down to 32 pg/mL. We used these
binding trajectories to train the microprocessor for future experiments. The assay
runs for 15 min to allow sufficient time for differentiable signals to emerge while
still providing rapid results for POC utility.
Each disposable stick, which is inserted into the detection module, is equipped
with eight sensors allowing for up to 8-plex protein detection simultaneously in a
single assay and permitting entire panels of markers to be monitored in real-time.
The signals detected by each sensor on the stick can be displayed to the user via col-
ored light-emitting diodes (LEDs) on the detection module. The microprocessor is
preprogrammed with tables that contain calibration curves for each target protein as
well as for the corresponding concentration thresholds (undetectable, low, medium,
and high) which are predetermined by physicians according to clinically relevant
therapy regimens (Fig.
7.14
b). As the assay runs, the colored LEDs dynamically
change and thereby present the results in real-time to the end user. The display of
the device can alternatively be equipped with a quantitative digital readout, but the
LED color reporting system shown here suffices to indicate relative levels of protein
content for untrained users. After a 15 min incubation period, the predicted signal
at saturation is compared with threshold values, and the microprocessor selects the
appropriate indicative color for each LED. For example, when a 10 ng/mL of p24
capsid protein was tested on the handheld device, a signal of 39 ppm was measured
