EFFICIENT IMPLEMENTATION OF ROBUST CUSUM ALGORITHM TO CHARACTERIZE
NANOGAPS MEASUREMENTS WITH HEAVY-TAILED NOISE
Javier Kipen
⋆
, Joakim Jald´ en
⋆
, Shyamprasad N. Raja
†
, Saumey Jain
†
⋆
Division of Information Science and Engineering (ISE), KTH, Stockholm, Sweden {kipen,jalden}@kth.se
†
Division of Micro and Nanosystems (MST), KTH, Stockholm, Sweden {shnr,saumey}@kth.se
ABSTRACT
Detection of bio-molecules through quantum tunneling currents
could lead to the next-generation DNA sequencing methods. In
order to analyze the stability of these sensitive devices, it is nec-
essary to characterize their conductance switching statistics. This
characterization can be realized by denoising the tunneling current
signal and clustering the outcomes. The first step can be done with
the CUSUM algorithm, which detects abrupt changes and has been
used in similar devices. We found heavy-tailed non-Gaussian noise
in the measurement setup of the experimental devices. This pa-
per suggests an approximation in the likelihood ratio step of the
CUSUM algorithm that is more robust than the simple Gaussian
noise assumption and, at the same time, is computationally more
efficient than computing the fitted true likelihoods.
Index Terms— CUSUM, robust, nanogaps, heavy-tailed
1. INTRODUCTION
Genome sequencing can decode the trove of information stored in
DNA and other nucleic acids. This information holds the potential
for developing targeted and personalized drugs for therapies. Some
recent technologies could significantly reduce the price of this pro-
cess. A good example was the success of the Oxford Nanopore Tech-
nologies DNA sequencers, which relies on modulated ionic currents.
It is believed that devices based on quantum mechanical phenomena
could further reduce costs and improve accuracy [1].
In this context, we consider the development of a next-generation
bio-molecular sensor based on quantum tunnel current measure-
ments. The sensor consists of a pair of electrodes separated by a
nanometer-sized gap enclosed by a microfluidic channel. Applying
a voltage bias over the electrodes induces a tunneling current that is
modulated by bio-molecules that pass the gap. Such sensors were
massively fabricated in parallel in our project by first generating
nano-wires with a method similar to the one described in [2] and
then generating a gap through electromigration [3] by applying a
current with the devices immersed in a chosen medium.
The last procedure has considerably different outcomes for each
medium in which the electromigration was performed. Some medi-
ums showed a higher yield of tunneling devices. We analyzed the
current stability of the devices for fixed voltage biases to compare
the devices. When the medium was nitrogen, half of the working
devices had a random telegraph signal (RTS) noise [4], which can
be due to the rearrangement of atoms. We refer to these devices as
switching devices. The proportion of devices with RTS noise for
other mediums was similar.
The measures signal can be modeled as a piece-wise constant
signal with clustered levels immersed in noise. In order to analyze
the stability of these devices, the current levels are associated with
conductance states. Then by analyzing the spread, duration, and val-
ues of these conductance levels, it can be determined whether these
devices are stable for bio-molecule measurements.
The CUSUM algorithm [5] was used to denoise the underlying
piece-wise constant signal, assuming that the noise was Gaussian.
However, the noise of the devices was heavy-tailed. The main con-
tribution of this paper is the development of a robust and computa-
tionally efficient version of the CUSUM algorithm for this noise.
2. METHODS
In the denoising step, we tested several approaches from [6], but
since the amount of data is large (recordings of minutes for hundreds
of devices at 200 kHz), the computation time was excessive, which
made the analysis unfeasible. A previous study about the automatic
processing of translocations through nanopores [7] used the CUSUM
algorithm to denoise the underlying piece-wise constant signal. This
algorithm is computationally cheaper than the methods mentioned in
[6], which makes it more suitable for the given measurements.
Fig. 1: Distribution fit on real data.
In our measuring setup, we observed heavy-tailed noise. A his-
togram of the noise values for one specific device is shown in Fig. 1.
When the electromigration was done in nitrogen, 70% of the switch-
ing devices presented a noise at 0V that fitted well to a mixture of
two Gaussian with the same zero mean. This proportion was simi-
lar for other mediums. The heavy-tailed noise is also present in the
measurements of simple resistances, so we concluded that it was due
to the instrument used to perform the measurements.
Assuming that the noise distribution is Gaussian for the CUSUM
algorithm, as in [7], is sub-optimal in this case. However, imple-
menting the algorithm for the Gaussian mixture is unfortunately
computationally more expensive due to repeated calculations of ex-
ponents and logarithms. We, therefore, propose an approximation to
ICASSP 2023 - 2023 IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP) | 978-1-7281-6327-7/23/$31.00 ©2023 IEEE | DOI: 10.1109/ICASSP49357.2023.10096779