Hardik J. Pandya

Accurate Characterization of Benign and Cancerous Breast Tissues: Aspecific Patient Studies using Piezoresistive Microcantilevers

Breast cancer is the largest detected cancer amongst women in the US. In this work, our team reports on the development of piezoresistive microcantilevers (PMCs) to investigate their potential use in the accurate detection and characterization of benign and diseased breast tissues by performing indentations on the micro-scale tissue specimens. The PMCs used in these experiments have been fabricated using laboratory-made silicon-on-insulator (SOI) substrate, which significantly reduces the fabrication costs. The PMCs are 260 μm long, 35 μm wide and 2 μm thick with resistivity of order 1.316×10(-3) Ω cm obtained by using boron diffusion technique. For indenting the tissue, we utilized 8 μm thick cylindrical SU-8 tip. The PMC was calibrated against a known AFM probe. Breast tissue cores from seven different specimens were indented using PMC to identify benign and cancerous tissue cores. Furthermore, field emission scanning electron microscopy (FE-SEM) of benign and cancerous specimens showed marked differences in the tissue morphology, which further validates our observed experimental data with the PMCs. While these patient aspecific feasibility studies clearly demonstrate the ability to discriminate between benign and cancerous breast tissues, further investigation is necessary to perform automated mechano-phenotyping (classification) of breast cancer: from onset to disease progression.

Design and fabrication of a flexible MEMS-based electro-mechanical sensor array for breast cancer diagnosis

The use of flexible micro-electro-mechanical systems (MEMS)-based devices provides a unique opportunity in bio-medical robotics such as the characterization of normal and malignant tissues. This paper reports on the design and development of a flexible MEMS-based sensor array integrating mechanical and electrical sensors on the same platform to enable the study of the change in electro-mechanical properties of benign and cancerous breast tissues. In this work, we present the analysis of the electrical characterization of the tissue specimens and also demonstrate the feasibility of using the sensor for the mechanical characterization of tissue specimens. Eight strain gauges acting as mechanical sensors were fabricated using poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT:PSS) conducting polymer on poly(dimethylsiloxane) (PDMS) as the substrate material. Eight electrical sensors were fabricated using SU-8 pillars on gold (Au) pads which were patterned on the strain gauges separated by a thin insulator (SiO2 1.0??m). These pillars were coated with gold to make them conducting. The electro-mechanical sensors are integrated on the same substrate. The sensor array covers a 180??m?????180??m area and the size of the complete device is 20?mm in diameter. The diameter of each breast tissue core used in the present study was 1?mm and the thickness was 8??m. The region of interest was 200??m?????200??m. A microindentation technique was used to characterize the mechanical properties of the breast tissues. The sensor is integrated with conducting SU-8 pillars to study the electrical property of the tissue. Through electro-mechanical characterization studies using this MEMS-based sensor, we were able to measure the accuracy of the fabricated device and ascertain the difference between benign and cancers breast tissue specimens.

Toward a Portable Cancer Diagnostic Tool Using a Disposable MEMS-Based Biochip

Goal: The objective of this study is to design and develop a portable tool consisting of a disposable biochip for measuring electrothermomechanical (ETM) properties of breast tissue. Methods: A biochip integrated with a microheater, force sensors, and electrical sensors is fabricated using microtechnology. The sensor covers the area of 2 mm and the biochip is 10 mm in diameter. A portable tool capable of holding tissue and biochip is fabricated using 3-D printing. Invasive ductal carcinoma and normal tissue blocks are selected from cancer tissue bank in Biospecimen Repository Service at Rutgers Cancer Institute of New Jersey. The ETM properties of the normal and cancerous breast tissues (3-mm thickness and 2-mm diameter) are measured by indenting the tissue placed on the biochip integrated inside the 3-D printed tool. Results: Integrating microengineered biochip and 3-D printing, we have developed a portable cancer diagnosis device. Using this device, we have shown a statistically significant difference between cancerous and normal breast tissues in mechanical stiffness, electrical resistivity, and thermal conductivity. Conclusion: The developed cancer diagnosis device is capable of simultaneous ETM measurements of breast tissue specimens and can be a potential candidate for delineating normal and cancerous breast tissue cores. Significance: The portable cancer diagnosis tool could potentially provide a deterministic and quantitative information about the breast tissue characteristics, as well as the onset and disease progression of the tissues. The tool can be potentially used for other tissue-related cancers.

Robot-Guided Atomic Force Microscopy for Mechano-Visual Phenotyping of Cancer Specimens.

Atomic force microscopy (AFM) and other forms of scanning probe microscopy have been successfully used to assess biomechanical and bioelectrical characteristics of individual cells. When extending such approaches to heterogeneous tissue, there exists the added challenge of traversing the tissue while directing the probe to the exact location of the targeted biological components under study. Such maneuvers are extremely challenging owing to the relatively small field of view, limited availability of reliable visual cues, and lack of context. In this study we designed a system that leverages the visual topology of the serial tissue sections of interest to help guide robotic control of the AFM stage to provide the requisite navigational support. The process begins by mapping the whole-slide image of a stained specimen with a well-matched, consecutive section of unstained section of tissue in a piecewise fashion. The morphological characteristics and localization of any biomarkers in the stained section can be used to position the AFM probe in the unstained tissue at regions of interest where the AFM measurements are acquired. This general approach can be utilized in various forms of microscopy for navigation assistance in tissue specimens.

MEMS-Based Flexible Force Sensor for Tri-Axial Catheter Contact Force Measurement

Atrial fibrillation (AFib) is a significant healthcare problem caused by the uneven and rapid discharge of electrical signals from pulmonary veins (PVs). The technique of radiofrequency (RF) ablation can block these abnormal electrical signals by ablating myocardial sleeves inside PVs. Catheter contact force measurement during RF ablation can reduce the rate of AFib recurrence, since it helps to determine the effective contact of the catheter with the tissue, thereby resulting in effective power delivery for ablation. This paper presents the development of a 3-D force sensor to provide the real-time measurement of triaxial catheter contact force. The 3-D force sensor consists of a plastic cubic bead and five flexible force sensors. Each flexible force sensor was made of a PEDOT:PSS strain gauge and a polydimethylsiloxsane (PDMS) bump on a flexible PDMS substrate. Calibration results show that the fabricated sensor has a linear response in the force range required for RF ablation. To evaluate its working performance, the fabricated sensor was pressed against gelatin tissue by a micromanipulator and also integrated on a catheter tip to test it within deionized water flow. Both experiments simulated the ventricular environment and proved the validity of applying the 3-D force sensor in RF ablation. [2016-0139]

High sensitivity square ring channel shaped MOSFET embedded pressure sensor integrated with a current mirror readout circuitry

This paper presents the design and simulation of a current mirror sensing based ring channel shaped MOSFET embedded pressure sensor. The pressure sensor is composed of two identical square ring shaped n-channel MOS transistors connected in current mirror configuration with its output transistor integrated on a silicon diaphragm. The diaphragm deflection results in the variation of drain current of embedded MOSFET due to altered channel mobility. Piezoresistive effect in MOSFET has been exploited for the calculation of strain induced carrier mobility variation under applied pressure. COMSOL Multiphysics and T-Spice are used to simulate the structural and electrical behaviour of the pressure sensor. Simulation results show that the pressure sensor has a sensitivity of approximately 407 mV/MPa in the pressure range of 0-1 MPa.

A Microscale Piezoresistive Force Sensor for Nanoindentation of Biological Cells and Tissues

We present the design and fabrication of a Micro-Electro-Mechanical Systems based piezoresistive cantilever force sensor as a potential candidate for micro/nano indentation of biological specimens such as cells and tissues. The fabricated force sensor consists of a silicon cantilever beam with a p-type piezoresistor and a cylindrical probing tip made from SU-8 polymer. One of the key features of the sensor is that a standard silicon wafer is used to make silicon-on-insulator (SOI), thereby reducing the cost of fabrication. To make SOI from standard silicon wafer the silicon film was sputtered on an oxidized silicon wafer and annealed at 1050 °C so as to obtain polycrystalline silicon. The sputtered silicon layer was used to fabricate the cantilever beam. The as-deposited and annealed silicon films were experimentally characterized using X-ray diffraction (XRD) and Atomic Force Microscopy (AFM). The annealed silicon film was polycrystalline with a low surface roughness of 3.134 nm (RMS value).Copyright

Integration of MEMS with nanostructured metal-oxide materials for improved sensors for volatile organic compounds

The primary aim of the present work is to lower the operating temperature of the metal-oxide based sensors for detection of volatile organic compounds (VOCs) without compromising the sensitivity of the device. For this purpose, nanostructured oxides of ITO, Cu and Zn have been explored. The oxides of Cu and Zn have been synthesized by a novel process of thermal oxidation of the respective metal layers in air ambient without using any seed or catalyst layer. On the other hand, nanostructured ITO was obtained by RF magnetron sputtering process. For the heating of the sensing layer, a Ni microheater has been integrated on the sensor chip. Micro-electro-mechanical Systems (MEMS) technology has been adopted for the fabrication of the complete sensor for achieving the desired operating temperature at reduced power level. The sensor was extensively tested for a variety of VOCs such as acetone, methanol, ethanol and IPA. The issues involved in integrating nanostructured oxides with MEMS technology are also addressed.

NANOSTRUCTURED ITO THIN FILMS BY RF SPUTTERING FOR ACETONE SENSOR

A sensor for detection of acetone vapors using nanostructured ITO thin film is reported. The ITO film was sputter-deposited on glass substrate using RF magnetron sputtering at 200 W RF power in argon atmosphere at 20 mTorr pressure. The film was then annealed at 450°C for 1h in air. The sensing area was kept to be 3 mm × 3 mm. Two aluminum pads of 7 mm × 4 mm size were formed using lift-off technique for electrical contacts. The crystallinity, microstructure, and acetone vapor-sensing properties were systematically investigated. The stability of the sensing films with aging and temperature variations was also investigated.

ITO Thin Films by RF Sputtering for Ethanol Sensing

The sensor for detection of ethanol vapours using RF sputter deposited ITO thin film on glass and Si substrates is reported. The principle of operation is the change of resistance of ITO film on exposure to ethanol vapours. The films were annealed at 450 ºC for 1h in air. The films were extensively characterized for their structural properties using XRD, SEM and TEM measurements. The sensing area was kept to be 3mm × 3mm and two aluminium pads of 7mm × 4mm size were formed using lift-off technique for electrical contacts. The stability of the sensing films with aging and temperature variations was also investigated. It is shown that sputtering parameters such as RF power strongly affect the sensitivity of detection.