Biomaterials

W13D1: Biosensors
Name:






An underlying theme to many X-men storylines is the hunting
down of mutants, called X-men, amongst the human
population. This group of mutants has a genetic mutation in
their X-gene that allows the mutants to develop superhuman
powers or abilities, sometimes perceived as threatening to
the human race. You work as a staff scientist for U.S. Senator
Kelly who is trying to track down all the mutants to eliminate
their perceived threat. You are designing a biosensor to
detect the X-gene mutation.

1. You start out thinking that it might be easier to get a
blood sample instead of making a biosensor that interacts
in vivo with blood. Explain why sample removal systems dont have to be biocompatible
but biofouling is still a major concern.









2. Due to the difficulty of obtaining a fresh blood sample, youve decided your sensor must
invasively contact the mutants blood to properly detect the mutation. Explain why any
sensor that causes physical damage leads to chemical changes in the local environment?
How can this affect the function of the sensor?








3. Previously used needle-based electrodes have been found to give accurate results in
vitro before and after producing erroneous values in vivo. Explain this phenomenon.


4. Youre testing your new X-gene sensor in a non-mutant human as a control. After 2
days, your sensor begins to register much higher levels of X-genes. Due to extensive
testing, you know that drift (signal change over time NOT associated with analyte
detection) is not a factor in these readings. Explain your findings.








5. You have designed an amperometric sensor that is being tested for detection in
blood of Protein-X for which the X-gene codes. The sensor is prepared by attaching
a capture antibody for Protein-X to a biosensor surface. When a Protein-X molecule
is captured onto the sensor, it generates changes in the measured electrical
resistance of the device.
a. The following results are achieved with test samples of protein-X in buffered
saline, blood, and plasma. In order to examine dose response over several orders
of magnitude, draw a curve for each set of data of 1/ vs. log[protein-X] on the
same plot. Can you explain the shape of the curves?
[Protein X]
Sensor Reading in Sensor Reading in Sensor Reading in
(ng/mL)
PBS ()
Blood ()
Plasma ()
.0001
5
0.7
3
.001
4.96
0.69
2.9
.01

4.8

0.69

2.86

.1

3.3

0.68

2.2

1.0

1.6

0.65

1.3

10

1.06

0.62

0.9

100

1.05

0.61

0.86

1000

0.6

0.85



b. Why does the data look different between the three curves? Explain whats
happening to the biosensor.

c. What is the sensitivity of the biosensor in PBS in the concentration ranges of

0.0001 to 0.01, 0.1 to 10, and 100 to 1000 mg/mL? Sensitivity is the ratio of
change in sensor output to change in analyte concentration. Sensitivity =

(| |)
10

d. Within which concentration range is the sensor most sensitive to Protein-X

concentration? Is the sensor more or less sensitive in plasma and blood?


e. Albumin is the most prevalent blood protein, and its plasma concentration is
~40 g/L. Assume that the non-specific biosensor signal in plasma at [Protein-X]
= 1 ng/mL comes from albumin attachment to the anti-Protein-X antibody.
Estimate the selectivity of the anti-Protein-X antibody for recognizing the target
Protein-X while not recognizing other proteins in the serum (such as albumin).
Selectivity is defined as:

[]
[]

f. Design three surface-blocking schemes to aid in the design of this sensor. Would
these schemes improve the sensitivity, selectivity, or both? Explain.










g. Why is the assumption that albumin is the main cause of fouling in plasma due to
its abundance alone erroneous?