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.

[1]  Kishore Sundara-Rajan,et al.  Interdigital sensors and transducers , 2004, Proceedings of the IEEE.

[2]  Arianna Menciassi,et al.  Miniaturization of biomedical micromachines , 2002, 2nd Annual International IEEE-EMBS Special Topic Conference on Microtechnologies in Medicine and Biology. Proceedings (Cat. No.02EX578).

[3]  Benjamin C. K. Tee,et al.  Skin-like pressure and strain sensors based on transparent elastic films of carbon nanotubes. , 2011, Nature nanotechnology.

[4]  Woo-Chang Choi.  Polymer Micromachined Flexible Tactile Sensor for Three-Axial Loads Detection , 2010 .

[5]  Yonggang Huang,et al.  Stretchable and Foldable Silicon Integrated Circuits , 2008, Science.

[6]  Wenjin Chen,et al.  Mechanical phenotyping of breast cancer using MEMS: a method to demarcate benign and cancerous breast tissues. , 2014, Lab on a chip.

[7]  A. Mata,et al.  Characterization of Polydimethylsiloxane (PDMS) Properties for Biomedical Micro/Nanosystems , 2005, Biomedical microdevices.

[8]  Pasqualina M. Sarro,et al.  Pressure, flow and oxygen saturation sensors on one chip for use in catheters , 2000, Proceedings IEEE Thirteenth Annual International Conference on Micro Electro Mechanical Systems (Cat. No.00CH36308).

[9]  T. Someya,et al.  Conformable, flexible, large-area networks of pressure and thermal sensors with organic transistor active matrixes. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[10]  A. Evans,et al.  Micromachined silicon cantilever paddles with piezoresistive readout for flow sensing , 1996 .

[11]  Jaydev P. Desai,et al.  Probabilistic Estimation of Mechanical Properties of Biomaterials Using Atomic Force Microscopy , 2014, IEEE Transactions on Biomedical Engineering.

[12]  D L Polla,et al.  Microdevices in medicine. , 2000, Annual review of biomedical engineering.

[13]  Hamid Ladjal,et al.  Mechanical phenotyping of mouse embryonic stem cells: increase in stiffness with differentiation. , 2011, Cellular reprogramming.

[14]  Hans-Jürgen Butt,et al.  A Sensitive Method to Measure Changes in the Surface Stress of Solids , 1996 .

[15]  Ueli Aebi,et al.  The nanomechanical signature of breast cancer. , 2012, Nature nanotechnology.

[16]  Alan G. R. Evans,et al.  Fabrication of improved piezoresistive silicon cantilever probes for the atomic force microscope , 1997 .

[17]  Andrew G. Gillies,et al.  Nanowire active-matrix circuitry for low-voltage macroscale artificial skin. , 2010, Nature materials.

[18]  H. Ibach,et al.  Adsorbate‐induced surface stress , 1994 .

[19]  Udo Lang,et al.  Towards fully polymeric MEMS: Fabrication and testing of PEDOT/PSS strain gauges , 2008 .

[20]  David J. Peichel,et al.  Precision micromotor for surgery , 2000, 1st Annual International IEEE-EMBS Special Topic Conference on Microtechnologies in Medicine and Biology. Proceedings (Cat. No.00EX451).

[21]  J. Bechhoefer,et al.  Erratum: ‘‘Calibration of atomic‐force microscope tips’’ [Rev. Sci. Instrum. 64, 1868 (1993)] , 1993 .

[22]  J. F. Greenleaf,et al.  Magnetic resonance elastography: Non-invasive mapping of tissue elasticity , 2001, Medical Image Anal..

[23]  Jaydev P. Desai,et al.  Microarray-facilitated mechanical characterization of breast tissue pathology samples using contact-mode Atomic Force Microscopy (AFM) , 2010, 2010 3rd IEEE RAS & EMBS International Conference on Biomedical Robotics and Biomechatronics.

[24]  C.R. Keese,et al.  A biosensor that monitors cell morphology with electrical fields , 1994, IEEE Engineering in Medicine and Biology Magazine.

[25]  T. Someya,et al.  A Rubberlike Stretchable Active Matrix Using Elastic Conductors , 2008, Science.

[26]  Thomas W. Kenny,et al.  Low‐stiffness silicon cantilevers for thermal writing and piezoresistive readback with the atomic force microscope , 1996 .

[27]  Katsuhiko Fujita,et al.  The Shift from “Hard” to “Soft” Electronics , 2002 .

[28]  J. Rao,et al.  Nanomechanical analysis of cells from cancer patients. , 2007, Nature nanotechnology.

[29]  W. Häberle,et al.  VLSI-NEMS chip for parallel AFM data storage , 2000 .

[30]  Wenjin Chen,et al.  Accurate characterization of benign and cancerous breast tissues: aspecific patient studies using piezoresistive microcantilevers. , 2015, Biosensors & bioelectronics.

[31]  S. Lacour,et al.  Stretchable gold conductors embedded in PDMS and patterned by photolithography: fabrication and electromechanical characterization , 2010 .

[32]  Pasqualina M. Sarro,et al.  Lateral nano-Newton force-sensing piezoresistive cantilever for microparticle handling , 2006 .

[33]  Michael C. McAlpine,et al.  Highly ordered nanowire arrays on plastic substrates for ultrasensitive flexible chemical sensors. , 2007, Nature materials.

[34]  Takao Someya,et al.  A large-area, flexible pressure sensor matrix with organic field-effect transistors for artificial skin applications. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[35]  J. Dual,et al.  Mechanical characterization of PEDOT : PSS thin films , 2009 .

[36]  James K. Gimzewski,et al.  Surface stress in the self-assembly of alkanethiols on gold , 1997 .

[37]  Benjamin C. K. Tee,et al.  Highly sensitive flexible pressure sensors with microstructured rubber dielectric layers. , 2010, Nature materials.

[38]  Thomas Thundat,et al.  Adsorption-induced surface stress and its effects on resonance frequency of microcantilevers , 1995 .

[39]  Gary K. Fedder,et al.  Endoscopic optical coherence tomography with a micromachined mirror , 2002, 2nd Annual International IEEE-EMBS Special Topic Conference on Microtechnologies in Medicine and Biology. Proceedings (Cat. No.02EX578).

[40]  Patrick J. French,et al.  Silicon sensors for use in catheters , 2000, 1st Annual International IEEE-EMBS Special Topic Conference on Microtechnologies in Medicine and Biology. Proceedings (Cat. No.00EX451).

[41]  Isao Shimoyama,et al.  Transparent conductive-polymer strain sensors for touch input sheets of flexible displays , 2010 .

[42]  Giovanni Saggio,et al.  Piezoresistive behaviour of flexible PEDOT:PSS based sensors , 2009 .

[43]  K. Hata,et al.  A stretchable carbon nanotube strain sensor for human-motion detection. , 2011, Nature nanotechnology.

[44]  K. Costa,et al.  Non-Hertzian approach to analyzing mechanical properties of endothelial cells probed by atomic force microscopy. , 2006, Journal of biomechanical engineering.

[45]  Hai Zhou,et al.  Electrospun PEDOT:PSS–PVA nanofiber based ultrahigh-strain sensors with controllable electrical conductivity , 2011 .

[46]  Robert D. Howe,et al.  Bayesian change‐point analysis for atomic force microscopy and soft material indentation , 2009, 0909.5438.

[47]  A F Mak,et al.  Estimating the effective Young's modulus of soft tissues from indentation tests--nonlinear finite element analysis of effects of friction and large deformation. , 1997, Medical engineering & physics.

[48]  John Hedley,et al.  Quantitative analytical atomic force microscopy: a cantilever reference device for easy and accurate AFM spring-constant calibration , 2004 .

[49]  J. Wegener,et al.  Electric cell-substrate impedance sensing (ECIS) as a noninvasive means to monitor the kinetics of cell spreading to artificial surfaces. , 2000, Experimental cell research.

[50]  J. Bechhoefer,et al.  Calibration of atomic‐force microscope tips , 1993 .

[51]  H. Rothuizen,et al.  Translating biomolecular recognition into nanomechanics. , 2000, Science.

[52]  Subra Suresh,et al.  Biomechanics and biophysics of cancer cells , 2007 .

[53]  Peter Fischer,et al.  The self-assembly, aggregation and phase transitions of food protein systems in one, two and three dimensions , 2013, Reports on progress in physics. Physical Society.

[54]  Udo Lang,et al.  Piezoresistive properties of PEDOT: PSS , 2009 .

[55]  Dennis E. Discher,et al.  Nuclear Lamin-A Scales with Tissue Stiffness and Enhances Matrix-Directed Differentiation , 2013, Science.