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436 || AWSAR Awarded Popular Science Stories - 2019
novel microfluidic platform capable of probing the electrical and mechanical properties of individual cells at a rapid throughput. In the process, we asked ourselves two important questions – first, does the progression of diseases correlate to biophysical changes at the single-cell level? and second, how does one quantify these changes so that they can be used in rapid and efficient diagnosis?
Toanswerthesequestions,wefirstchose a disease model. Given that diabetes is the fastest growing disease in India, we yearned to understand the changes in the biophysical and rheological properties of lymphocytes in patients with diabetes. Thousands of individual lymphocytes were allowed to flow through a polydimethylsiloxane microchannel having a narrow constriction (5 μm) at the centre to mechanically squeeze the cells. This constriction was placed in between two pairs of co-planar microelectrodes made of gold, with each pair consisting
of one source and one
measurement electrode. The
gap between the electrodes
was comparable to the size
of the cells (lymphocyte),
and the impedance between
them was measured using an
external measurement setup
at a cell-specific frequency
(800 kHz). As the lymphocytes
traversed over each electrode
pair, the impedance measured
by the system was altered,
enabling one to measure the
electrical properties of the cell.
A differential measurement
principle was employed in
which there were two peaks
positive and negative in
the measurement signal, corresponding to the relative
impedance change of the entire
system. Analysing the time difference between the generated electrical signals further allowed us to estimate the time required by the cell to squeeze through the constriction (termed as transit time). This transit time is an effective way of comparing the mechanical properties of cells with varying degrees of deformability or stiffness. Thus, the platform enables the independent and simultaneous measurement of electrical and mechanical properties of lymphocytes at high throughput. Additionally, the platform compares the electrical signals from the lymphocytes in two states one: in an undeformed state prior to any mechanical squeezing and two: post squeezing across a mechanical constriction.
One might ask, ‘What additional information can we get from analysing electrical signals from these cells?’ A cell is essentially a complex union of a cytoskeletal network, lipid membrane, proteins, DNA,
ion channels and many more components that give rise to its fundamental electrical properties. The microscopic world of cells, therefore, has many parallels with electrical circuitry. Grossly simplified, the cytoplasm of the cell can be considered as a simple resistor and the cell membrane as a capacitor. In other words, a cell can be represented as a resistor and a capacitor in series. It is well known that, under diabetic conditions, increased oxidative stresses and blood glucose levels can alter the framework of many cell components, particularly lymphocytes. These ultimately get translated into changes in its electrical properties. Using our technique, it becomes
Without the progression of this critical technology, it would be virtually impossible to manipulate cells according to one’s whims and fancies. Using micro and nanofabrication techniques, we, at the Micro and Nano Fluidics Lab and the Complex Systems and Molecular Sensing Lab of the Indian Institute of Science, have developed a novel microfluidic platform capable of probing the electrical and mechanical properties of individual cells at a rapid throughput.