exploring mems as transducers and electrophysiological characterisation of cells in healthcare...

School of Medical Science and Technology, Indian Institute of Technology -Kharagpur

School of Medical Science and Technology Indian Institute of Technology Kharagpur

EXPLORING MEMS AS TRANSDUCERSand

ELECTROPHYSIOLOGICAL CHARACTERISATION OF CELLS IN HEALTHCARE APPLlCATIONS

Soumen [email protected]


OUTLINE OF THE TALKEvolution of microelectronicsIntroduction to MEMS LithographyWhy siliconCritical issues in Microsystem

technologyScaling lawsConclusions


EVOLUTION OF MICROELECTRONICSDevice (Transistor) (1947)

Silicon Planar Technology (1954)

Integrated Circuits (1958)

VLSI Micromachining / SOP / SOC MEMS (1970)

ULSI / Nano CMOS NEMS

MARKET DEMANDS…..Present to Future Higher speed Low power consumption Multi to Mega function Functional convergence (digital + analog + RF + optical)System in package: Convergence of computing, communication, consumer & Biomedical

Transceive voice+ massive data (e-mails, Internet, Camera)

MEMS micro gear-train bySandia National Laboratories

DRAM chip: 200 M transistors, Wiring length 8–10 m, feature size 35 nm, Supply < 1V

http://www.motorola.com/consumer/v/index.jsp?vgnextoid=718099cede15a010VgnVCM1000008206b00aRCRD&show=productHome


Transistor (Bipolar/MOS) to Integrated Circuits, VLSI/ULSI/SOC PCB based circuits Photolithography and silicon planar technology Linear bipolar ICs Bipolar digital ICs, TTL, ECL, IIL PMOS, NMOS, CMOS LSI / VLSI chips Device size shrinking, chip size increasing, speed and

power dissipation improving Microprocessors, microcomputers DSP chips On-chip analog-digital functions , SOC Nanoscale ICs


Moore’s Law Gordon Moore of Intel predicted in 1965 that “the number of

transistors per chip would double every 2 years”.Moore’s law led to the development of NanoCMOS

approaching 20 nm minimum feature with about a billion transistors per chip.

But conventional CMOS cannot go beyond 0.5 nm gate oxide. Moore’s law is steadily loosing validity in traditional IC technology.

“Cramming More Components Onto Integrated Circuits” by G. MoorePublication: Electronics, April 1965

2X transistors every 2 years

Traditional Scaling Era

40+ Years of Moore’s Law at INTEL: From Few to Billions of Transistors

END OF TRADITIONAL SCALING ERA ~ 2003


Nano CMOS TechnologyTechnology nodes ( min. feature size / gate

length) scaling down as : 350 nm, 250 nm, 180 nm, 150 nm, 130 nm, 90 nm, 65 nm, 45 nm, 30 nm, 22 nm.

Effective gate oxide thickness (EOT) shrinking from 80 nm to 1 nm (10 A)/ 4 to 5 atomic layers.

Subthreshold leakage current and GATE DIRECT TUNNELING CURRENT increase significantly. GDTC was not considered in previous designs.

Metal and polySi interconnect line width shrink below 100 nm. Contact holes and vias approach 100-200 nm. Interconnect resistance and RC delay increase appreciably.

Copper metallisation, CoSi / NiSi and chemical-mechanical polishing/planarisation (CMP) help in reducing resistance and RC value. But it reaches a limit.


Feynman’s Vision (1959)“There is plenty of room at the bottom”

“The entire encyclopedia could be written

on the head of a pin”

“ ……fabricate a motor with a volume less

than 1/64 of an inch on a side”


Advantages: Size reduction Cost effective Improved sensitivity Integration with signal conditioning circuit Low power consumption

Due to the miniature size and complex geometry of the 3-D mechanical structures, fabrication of MEMS devices is clearly beyond the means of traditional machine tools.

Evolved from silicon planar integrated circuit technology

MEMS (Micro Electro Mechanical Systems) is the integration of mechanical and electrical components on a common substrate to produce a system of miniature dimensions through the use of microfabrication technology. Operate in different energy domains (thermal, mechanical, chemical, magnetic, electrical, optical, biological energy domains) to produce/actuate electrical signal.


MEMS – Tiny TransducersAccelerometers,Gyroscopes,Pressure sensors,Position Sensors,Micro Gears,Micro Hinges,

Drug delivery,Microgrippers,Microfluidics,Lab on a Chip,Gas Sensors,

Bio-MEMS

Fluxgates, Hall Effect sensors,

MAGNETIC SENSORS MOEMSMicro mirrors,Micro Lens,

RF-MEMSTunable Inductors,RF Switches.

Flow sensors,Micro heaters,Micro Reactor,

Mechanical

Biological/ Chemical

Magnetic Optical

Communication

Thermal

Untreated


MEMS are interdisciplinary in their design, fabrication, and operation. They encompass many aspects ofEngineering

Mechanical (structures and phenomena: bending, deflecting, oscillations, vibrating; fluid dynamics…)

Electrical (electrical signals: detected, generated, processed; optoelectronics; Integrated circuits and devices…)

Chemical and Biochemical (reactions, processes, and kinetics… of many systems including living organisms)

Science Physics and Biophysics (external world vs. materials/properties

including living organisms at macro and nano scale) Chemistry, biochemistry, and physical chemistry (step more from

corresponding engineering disciplines towards basic answers) Biology (macro and nano effects in plants, animals, and humans

observed by smart transducers)Technology

Macro ex. Fluidics and large mechanical structures Micro ex. µm scale dimension of transducers, and Nano ex.nanodevices CNT, nanoprobes ….)


Integration of Various Science and Engineering Fields

Very powerful performance possible but difficulty in realization comes due to the interdisciplinary character of MEMS


Building BlocksMajor components in MEMS systems include

Design Much more difficult than IC designs due to the interdisciplinary

character of MEMS Design includes packaging

Packaging is one of the most challenging step both in design and realization

Transducers must be integrated with electronics Integration with ICs is another challenge for MEMS due to difficult

issues of process compatibility Fabrication

Silicon technology is widely used in MEMS with new step added Dimensions are usually much larger than those in ICs even for nano-

transducers. To feel NANO you do not need to be in the nano-scale size!

Other materials are included to perform required functions of transducers

MEMS are frequently integrated with fluidics (polymers, glass…) Materials

Materials that can perform required functions (thermo, piezo-, magneto-resististance…)

Interaction with fluidics (half-cell potential, corrosion…)


MICROMACHININGMicromachining is defined to be a process technology for shaping silicon or other material to realize 3-D MEMS structure by chemical etching technique Evolved from silicon planar integrated circuit technology Completely different from conventional machining process

Micromachining has become a dominant and fundamental technology in the fabrication of microsensors, microactuators and microstructures

MEMS devices are fabricated by Micromachining process.


ADVANTAGES of MEMS


MICROCHIP AND MEMS DEVELOPMENT


MICROFABRICATION PROCESS


Basics of Lithography

Lithography is used to describe as, a process in which a layer of material, sensitive to photons, electrons or ions, is selectively exposed following a particular pattern/image to transfer that pattern to the wafer.

“Lithos” (stone) + “graphein” (write) = Lithography , which means “ writing a pattern on stone”

Why lithography? Device miniaturization to achieve the technology

goals. Flexible technique. Enhanced properties, i.e. transport phenomenon, Fantastic characteristics, quantum confinement

effect.


Standard Photolithography:

Photolithography

apply resist

mask alignment/exposure

develop

etching

resist removal

• Spin coat radiation sensitive polymer - Resist

• Expose layer (through mask or direct write)

• Develop• Etch away or deposit

material

Basics of Lithography


Resolution Limit:Contact Lithography, Projection Lithography: directly dependent on wavelengthDecreasing feature sizes require the use of shorter .Can’t go farther: From this point we

need EBL.

Why e-beam lithography?Optical effect: Diffraction

Intensity profile produced by a spatially coherent beam as it passes through a slit

http://electroiq.com/blog/2013/page/110/


NanolithographyConventional EB and Ion Beam Direct

Writing / X-ray Lithography are highly capital intensive, not suitable for batch processing

Alternate lithography techniques for batch fabrication :Nanoimprint Lithography : Stamp-and-

Repeat / Stamp-and-Flash Microcontact Printing LithographyScanning Electron Probe Nanofabrication


electronic interface

computer

Expose:The E-beam is turned on/off and directed in a prearranged pattern over the surface of the resist.

There are two types of scanning system:(1)Raster scan, (2) vector scan.

Basic process for EBL cont..


Basic process for EBL

Surface preparation E-resist coating Soft bake Expose

Develop

Hard bakeInspection

Metal deposition/Etch Resist Strip Final InspectionTypical operations cycle of EBL


Proximity effect Backscattering causes the electron beam to broaden and expose a large volume of resist then expected.

The proximity effect places a limit on the minimum spacing between pattern feature. This is a limiting factor of high resolution lithography.

Depends on the pattern density and the substrate material, as well as parameters of the EBL exposure. Acceleration voltage Electron dose

Parametric effect cont..


Why Silicon for MEMS ?

The largest silicon micromachining applications to date, pressure and acceleration sensors, have been enabled primarily by two factors:

Excellent mechanical performance of silicon enabling it effectively to replace a majority of all other sensing technologies

The existing infrastructure of the mainstream IC industry, enabling development of products offering an unmatched price-to-performance ratio.


Mechanical performance of siliconSilicon and its derivatives (SiO2, Si3N4) are some of the best

electrically characterized materials in the world.

Based on known characterization of silicon, it can be classified as the best material for mechanical sensors. Silicon mechanical strength is comparable to (even higher than) steel, but at a lower density and better thermal conductivity.

Parameter Steel Silicon UnitsYield strength 4.2 (max) 7.0 1010 dyne cm-2

Young’s modules 2.1 1.9 1012 dyne cm-2

Density 7.9 2.3 G cm-2

Thermal conductivity

0.97 1.57 W cm-10 C-1


Why Silicon for Microsensors ? Lack of mechanical and thermal hysteresis, and long-term drift: For all

mechanical sensors the measure of excellence and performance limit is defined by the achievable mechanical and thermal hysteresis, and long-term stability. Silicon delivers good performance on each low-cost wafer, thanks to its extremely pure, defect-free crystalline structure.

High sensitivity to stress: The piezoresistive effect in silicon has a stress sensitivity two orders of magnitude larger than that of metal strain gauge, which enables fabrication of the high output devices with simple electronics

Batch manufacturability: The capability of manufacturing completed mechanical structures simultaneously on multiple wafers, each carrying multiple devices, forms the revolutionary aspect of the silicon micromachining technology - batch manufacturability.

Besides the excellent performance, silicon brings significant support from the established mainstream electronic industry, specifically:

Access to ultra-pure materialAccess to advanced semiconductor processesAvailability of the high volume packaging technologiesAccess to high volume manufacturing equipmentAn available base of educated silicon processing technologists


Unique Processes for MEMS

In addition to thatDouble Sided Alignment and LithographyEtch – Stop ProcessesDeep Reactive Ion Etching (DRIE)Sacrificial Layer EtchingWafer BondingDeposition of Special FilmsLIGA / Micromolding / NIL / MCPSpecial Packaging Techniques

Virtually all micro fabrication processes used for ICs are used for silicon-based MEMS and microsystems

Photolithography / Electron Beam Lithography Diffusion / Implantation/ Oxidation CVD / LPCVD / PECVD Vacuum Deposition / DC-RF Sputtering Wet Chemical Etching – Isotropic / Anisotropic Dry Etching – Plasma, RIE, RIBE


Bulk Micromachining Surface Micromachining Wafer Bonding LIGA/SLIGA and LIGA-Like Others

i) 3-D Lithographyii) Laser Micromachining

MEMS Technologies


Silicon Micromachining

Bulk Micromachining:Using single crystalline silicon wafer, the bulk material of the substrate along thickness direction is dissolved / etched by wet chemical etchant to realize various 3-D micromechanical structures

Device thickness is controlled by etching/ diffusion Mechanical properties of bulk silicon is preserved Alignment required for top and bottom side of wafer Require etch stop mechanism

MicromachiningBulk micromachining

Surface micromachining


Bulk Micromachining

Bulk micromachining along crystallographic planes


This technology is based on depositing and etching structural and sacrificial films. After deposition of thin film, sacrificial layer is etched away, leaving a completely assembled microstructure

Maximum possible thickness of the microstructure is limited to that of the deposited film

Surface Micromachining


Surface Micromachining


MICROSYSTEMS


Integrated MicrosystemsMiniature Mechanical Systems with Micron Feature SizeBatch Fabricated – No AssemblyExploits Microelectronics InfrastructureCommon Technology Base for Sensors, Actuators and Electronics


Integrated Microsystems


Microsystems Technology Motivation :Quality factor improvement in quality X reduction in costs

(per element) 107 (for microelectronics), 102 (technology in steel product

Thus “technology leap” given to microelectronicsQuestions ?

Would it not be possible the implementation of microelectronics in industrial scale to non-electric problems as well ( mechanical, optical or fluidic structures)?

Would it not be possible to develop the analog of the microprocessor, i.e. the “micro-systems”?

Would it not be possible to have this systems attain the maximum level of performance?


Major ProblemsInterface - a great number of possible forms of energy and

information transmissions have to be coped with.A great deal of novel technique has to be developed in

micro systems technology in order to handle information transmission by electric, acoustic, optical, thermal, fluidic or other means into the systems and out of the systems.

When the systems is applied in medical engineering, e.g. as a minimally invasive therapeutic system, drugs or biological substances must be handled by the system.These requirements mean a great challenge to the packaging and connection techniques in micro systems technology.


Implantable wireless microsystems Incorporates MEMS based transducers Have on-board power supply or powered from outside

by inductive coupling Communicate bi-directionally through RF interface Have on-board signal processing capability Constructed using biocompatible materials Use advanced packaging techniques

MICROSYSTEM COMPONENTS

Transducers are interfaces between tissue and readout circuitry and their performance is critical to the success of overall microsystem. Long term stability is an issue.

Transducers suffer poor S/N ratio, thus, requires on-board interface electronics. Post or integrated CMOS processing or hybrid processing technique is used for fabrication of the microsystem. Power consumption is a major consideration particularly for implantable devices, thus DSP is done outside the body.


Packaging and encapsulation is a challenging task. It must accomplish to 1) product electronics from harsh environment while providing access window for transducer to interact with the desired measurand, 2) Protect body from hazardous materials in microsystem. The degree of protection required for implantable systems depends on required life time of the device. Conventional packaging technique may not be suitable like glass-metal sealing is not batch scale technique, titanium encapsulation is not suitable for data transmission.

Choice of power source depends on implant life time, system power consumption, mode of operation (continuous or intermittent) and size. Battery is used for low power system with limited lifetime. Inductive powering is an alternative approach for large power requirement. Fuel cell and thin film batteries are being explored.

Bidirectional wireless communication is essential for implantable microsystem. Various modulation (AM, FM, and other pulse modulation) methods are used for inward and outward data transmission. The choice of transmission frequency is a trade off between adequate miniaturisation and tissue loss.

MICROSYSTEM COMPONENTS


Resonance shift due to single Cell

A gold dot, 50 nm fused to the end of a cantilevered oscillator. A one-molecule-thick layer of a chemicaldeposited on the gold adds a mass of about 6 attograms, which is measurable.

Silicon neural probe arraysKewley et al, Sensors Actuators 58, 1997

Cell-based biosensor with microelectrode array

Electrostatic micromotorFan Long-Sen et. al, Sensors Actuators 20, 41- 47

Silicon micro-needleChoi et al, Biomed. Microdev.,

2007

www.hgc.cornell.edu/biomems.html

Glimpse of BioMEMS


BioMEMS Activity @ IIT KharagpurProf-In-Charge: Dr. Soumen Das, Associate ProfessorProf-In-Charge: Dr. Soumen Das, Associate Professor

School of Medical Science & Technology, I. I. T. Kharagpur, INDIA 721302School of Medical Science & Technology, I. I. T. Kharagpur, INDIA 721302E-mail: [email protected]: [email protected]

Present R & D focusPresent R & D focus Flexible device/electronic for Flexible device/electronic for biomedical app.biomedical app.

Label-free Separation of Label-free Separation of Biological CellsBiological Cells

Funding/Collaboration: NPMASS, Govt. of India; ISRO, India; TI India, Bangalore

The real world dealing more with chemical, biological, mechanical rather than electrical domain only necessitates biomedical sensors involving 3D bio-microelectromechanical (BioMEMS) systems for transforming sensible bio-signals into a measurable output.

MEMS flow sensorNi-Cr resistor

on polymer

Technology for fluid flow at low power Micro-thruster for generation of thrust by the phase change of fluid

Silicon MEMS sensor for healthcare monitoringAccelerometer

Microfluidic system for cell manipulation

Microfluidic chip

Flexible electronics

Micro-structuring of polymer -Array of micropillars on SU-8, PDMS

Deposition and patterning of Al, Au and NiCr thin films on flexible polymer for BioMEMS applications

Development of MEMS Based Flexible Flow Sensor for Health Care Monitoring

HeaterSubstrate

CatheterArtery (Aorta)

Catheter with sensor against blood flow

direction

Flexible device concept / sensor bending

Wrapped Sensor

Thermocouple

Electric Probes

Microheater

Fabricated sensor

Flow Measurements

Simulated temp. distribution

Sensor Test Setup

Cells are separated based on their electrical property which changes with disease progressions, viability of cells

Electrical Characterization of Cells

Applications:•Cellular behavior•Disease detection•Cytotoxicity effect•Cell signal transduction

IEEE Trans Biomed Eng 2013. DOI:10.1109/TBME.2013.2265 319IEEE J of MEMS, 2013. DOI 10.1109/JMEMS.20IOP, JMM, 19, 2009;Microsystem technology,15, 2009


In this era of “think small,” one would intuitively simply scale down the size of all components to a device to make it small. Unfortunately, the reality does not work out that way.It is true that nothing is there to stop one from down sizing the device components to make the device small. There are, however, serious physical consequences of scaling down many physical quantities.Scaling laws that will make engineers aware of both positive and negative physical consequences of scaling down machines and devices.At very large scale physical problems are handled using relativity, where as at very small scale it is handled by quantum mechanics. Relative magnitude of different forces changes with the characteristic size of a system.

Effect of miniaturisation: Scaling Laws


WHY SCALING LAWS?Miniaturizing machines and physical systems is an ongoing effort inhuman civilization that comes from our market demands for: Intelligent, Robust, Multi-functional and Low cost consumer products has become more stronger than ever.

The only solution to produce these consumer products is to packagemany components into the product –making it necessary to miniaturize each individual components.

Miniaturization of physical systems is a lot more than just scaling downDevice components in sizes.Some physical systems either cannot be scaled down favorably, or cannot be scaled down at all! Scaling might favor smaller devices ( e.g., faster, less power, etc) but it might also disfavor miniaturization (e.g., smaller power sources last less long and small actuators exert less force).Scaling laws thus become the very first thing that any engineer would do in the design of MEMS and microsystems.It is of two types: 1. Scaling in Geometry: Scaling of physical size of objects

2. Scaling of Phenomenological Behavior: Scaling of both size & material characterizations


Effect of miniaturisation: Scaling Laws

Scaling laws are rules used to predict how a system will behave as it changes its size. Scaling laws deal with the structural and functional consequences of changes in size or scale among otherwise similar structures.The three parameters that can be changed when the size of a structure is increased/decreased are:Dimensions (e.g., thicker walls)Materials (e.g., from brick to steel)Design (e.g., from compression to tension elements)

Scaling in Geometry: Volume (V) and surface (S) are two physical parameters that are frequently involved in machine design.Volume leads to the mass and weight of device components.Volume relates to both mechanical and thermal inertia. Thermal inertia

is a measure on how fast we can heat or cool a solid. It is an important

parameter in the design of a thermally actuated devices Surface is related to pressure and the buoyant forces in fluid mechanics. For instance, surface pumping by using piezoelectric means is a practical way for driving fluids flow in capillary conduits.When the physical quantity is to be miniaturized, the design engineer must weigh the magnitudes of the possible consequences from the reduction on both the volume and surface of the particular device.


Volume of body increased, its surface area does not increase in same proportion, but in proportion to 2/3 power of volume

If linear dimension is decreased by 10 times, its area (S) is decreased by 100 times and volume (V) is decreased by 1000 times. S ~ V2/3,

Thus smaller bodies have, relative to their volume larger surface area than larger bodies of same shape.

For elephant S/V ~ .0001/mm, butterfly 0.1/mm. It requires little energy and power, and thus low consumption of food to fly, whereas elephant has huge appetite for food to generate sufficient energy for even small movement.

Linear extrapolation of length comes easy to us, but we are quickly at a loss when considering the implications that shrinking of length has on surface area to volume ratios (S/V) and on the relative strength of external forces (actuator mechanisms) e.g. capillary tubes: weight scales as l3 and surface tension as l.


Scaling laws:Time – l0 Mass – l3 Gravitational force - l3 Friction - l2

Surface tension - l1 Velocity - l1 Diffusion - l1/2 Thermal loss - l2

Cantilever deflection

2

2

4/

)(2)(3 s

stslg

Assuming all dimensions are equally scaled down,

2

4

23

tlg

Deflection shrinks faster than device dimension

Mechanical Resonance

10

31

0

,21

Lf

LmLk

mkf

1

0

53

0

,21

LfLILkI

kf

Cantilever Beam Torsional resonator


MEMS and microsystems fields will lead to mature products in a number of industrial applications as well as provide inspiration for research in unexplored areas.

Diverse set of materials used in microsystems is steadily expanding to take advantage of properties ranging far beyond those found in silicon alone.

Critical issues associated with fabrication and packaging needs to be examined in depth to achieve high throughput and yield.

Both fabrication flows and unit processes still involve considerable innovation.

MEMS packaging is also more difficult than in microelectronics because many sensors must directly contact the environment they are trying to measure, and for many devices, packaging at the wafer level is essential both for fabrication yield and for operating performance.

Conclusions