Panasonic, core partner within imec’s
Human++ program, and imec today presented at the International Electron Devices
Meeting in San Francisco various critical components of a biomedical lab-on-chip
sensor enabling fast detection of Single Nucleotide Polymorphisms (SNPs) in
DNA, such as a miniaturized pump for on-chip generation of high pressures, a
micropillar filter optimized for DNA separation achieving world-record resolution,
and a SNP detector allowing on-chip detection using very small sample volumes.
A SNP is a single nucleotide replacement in a DNA sequence which can result
in different reaction by people to pathogens and medicines. Detection of these
SNP’s is therefore becoming increasingly important with the move towards
more personalized healthcare.
Existing methods to detect SNP’s require many sample processing steps
in dedicated medical tools at medical laboratories. Such tests are labor intensive,
time-consuming and expensive. Moreover, rather large blood samples are needed.
A lab-on-chip device can bring huge advantages both to the patient and the healthcare
system. Such devices enable fast, easy-to-use, cost-effective test methods which
can be performed at regular times in a doctor’s office or even near the
patient’s bed. This is very interesting for point-of-care applications
such as personalized medicine.
By combining advanced micro-electronic fabrication processes with heterogeneous
integration, imec and Panasonic aim to realize a state-of-the-art microfluidic
device for SNP detection. In order to do this, advanced microfluidic components
have been fabricated and optimized, such as a miniaturized pump for on-chip
generation of high pressure, a micropillar filter optimized for DNA separation
achieving world-record resolution, and a SNP detector allowing on-chip detection
using very small sample volumes.
The entrance unit of the SNP detection system samples very small volumes of
blood. This entrance unit features a miniaturized high-pressure pump based on
an advanced conductive polymer actuator. After optimization, the actuator generates
high pressures (up to 3MPa) at low voltage (~1.5V). The high pressure is essential
to generate a fluid flow through the next unit of the SNP detection system.
The on-chip low voltage operation is important because it opens the path to
autonomy and portability of the lab-on-chip device.
Next, the DNA separation unit featuring an advanced micro-pillar array filter
was developed. This deep-UV patterned silicon pillar array was realized using
advanced MEMS technology. It consists of many micron-scale pillars, being typically
20µm high and with 1-2µm inter-pillar distance. The pillar array
is used for DNA separation based on ion-pair reversed-phase (IR-RP) liquid chromatography.
Imec and the VUB (Vrije Universiteit Brussel), a scientific partner of imec,
optimized the pillar-based IR-RP liquid chromatography technique for DNA separation.
This resulted in the first miniaturized on-chip system that enables fast and
highly selective separation of short, double stranded DNA strands which only
differ 50 base pairs in length. The resolution of the system is the highest
in the world and proves the potential to handle 5 SNPs at the same time in the
final SNP detection system.
The other functional units of the SNP detector are a unit for DNA extraction
and polymerase chain reaction (PCR) using heaters and temperature sensors, and
a SNP detection unit based on electrochemical sensors. The miniaturization of
these sensors was of crucial importance, since the minimum required sensor volume
determines the blood sampling volume needed for the SNP detection, and hence
the dimensions of all components of the device. Scientists of Panasonic and
imec demonstrated SNP detection capabilities using on-chip sensors handling
a volume as small as 0.5µL.
Imec’s Human++ program provides a multidisciplinary R&D platform
for industrial partners to collaborate on finding industry-relevant solutions
for future healthcare and wellness needs by combining nanoelectronics and biotechnology
into heterogeneous systems for diagnosis and therapy. Human++ partners build
on imec’s 25 years of expertise in micro- and nanoelectronics and expertise
in several healthcare-relevant domains.