Internalization of subcellular-scale microfabricated chips by healthy and cancer cells.

Continuous monitoring of physiological parameters inside a living cell will lead to major advances in our understanding of biology and complex diseases, such as cancer. It also enables the development of new medical diagnostics and therapeutics. Progress in nanofabrication and wireless communication has opened up the potential of making a wireless chip small enough that it can be wholly inserted into a living cell. To investigate how such chips could be internalized into various types of living single cells and how this process might affect cells' physiology, we designed and fabricated a series of multilayered micron-scale tag structures with different sizes as potential RFID (Radio Frequency IDentification) cell trackers. While the present structures are test structures that do not resonate, the tags that do resonate have similar structure from device fabrication, material properties, and device size point of view. The structures are in four different sizes, the largest with the lateral dimension of 9 µm × 21 µm. The thickness for these structures is kept constant at 1.5 µm. We demonstrate successful delivery of our fabricated chips into various types of living cells, such as melanoma skin cancer, breast cancer, colon cancer and healthy/normal fibroblast skin cells. To our surprise, we observed a remarkable internalization rate difference between each cell type; the uptake rate was faster for more aggressive cancer cells than the normal/healthy cells. Cell viability before and after tag cellular internalization and persistence of the internalized tags have also been recorded over the course of five days of incubation. These results establish the foundations of the possibility of long term, wireless, intracellular physiological signal monitoring.

ISFET pH Sensitivity: Counter-Ions Play a Key Role.

The Field Effect sensors are broadly used for detecting various target analytes in chemical and biological solutions. We report the conditions under which the pH sensitivity of an Ion Sensitive Field Effect transistor (ISFET) sensor can be significantly enhanced. Our theory and simulations show that by using pH buffer solutions containing counter-ions that are beyond a specific size, the sensor shows significantly higher sensitivity which can exceed the Nernst limit. We validate the theory by measuring the pH response of an extended gate ISFET pH sensor. The consistency and reproducibility of the measurement results have been recorded in hysteresis free and stable operations. Different conditions have been tested to confirm the accuracy and validity of our experiment results such as using different solutions, various oxide dielectrics as the sensing layer and off-the-shelf versus IC fabricated transistors as the basis of the ISFET sensor.

Mass fabrication and delivery of 3D multilayer µTags into living cells.

Continuous monitoring of in vivo biological processes and their evolution at the cellular level would enable major advances in our understanding of biology and disease. As a stepping stone towards chronic cellular monitoring, we demonstrate massively parallel fabrication and delivery of 3D multilayer micro-Tags (µTags) into living cells. Both 10 µm × 10 µm × 1.5 µm and 18 µm × 7 µm × 1.5 µm devices containing inductive and capacitive structures were designed and fabricated as potential passive radio-frequency identification tags. We show cellular internalization and persistence of µTags over a 5-day period. Our results represent a promising advance in technologies for studying biology and disease at the cellular level.