Embed Size (px)
Citation preview
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. 55, NO. 2, FEBRUARY 2008 485
Analog CMOS Design for Optical CoherenceTomography Signal Detection and Processing
Wei Xu, David L. Mathine, Member, IEEE, and Jennifer K. Barton*, Member, IEEE
Abstract—A CMOS circuit was designed and fabricated foroptical coherence tomography (OCT) signal detection and pro-cessing. The circuit includes a photoreceiver, differential gainstage and lock-in amplifier based demodulator. The photoreceiverconsists of a CMOS photodetector and low noise differentialtransimpedance amplifier which converts the optical interferencesignal into a voltage. The differential gain stage further amplifiesthe signal. The in-phase and quadrature channels of the lock-inamplifier each include an analog mixer and switched-capacitorlow-pass filter with an external mixer reference signal. Theinterferogram envelope and phase can be extracted with thisconfiguration, enabling Doppler OCT measurements. A sensitivityof 80 dB is achieved with faithful reproduction of the interfero-metric signal envelope. A sample image of finger tip is presented.
Index Terms—Biomedical imaging, CMOS analog integratedcircuits, optical tomography.
I. INTRODUCTION
OPTICAL coherence tomography (OCT) is a noninvasivebiomedical imaging technique with micron-scale res-
olution and cross-sectional imaging capability [1]. OCT hasdeveloped rapidly in the past decade into a versatile imagingtechnology. OCT applications have been reported in Ophthal-mology, Dermatology, Gastroenterology, Dentistry, Cardiology,and Urology, among other fields [2]–[4].
Time domain OCT is based on low-coherence interferometrytheory, with depth scanning enabled by changing the pathlengthin the reference arm. Typically, a discrete photoreceiver, analogfiltering and demodulation are used for signal detection andprocessing. This analog instrumentation may be bulky andexpensive. Demodulation may also be performed digitally,but real-time operation generally requires a high-performancedigital signal processor. Parallel OCT imaging systems canachieve high-quality, real-time imaging and potential elimina-tion of lateral scanning. For such systems, analog demodulationwith discrete components may become impractical, while highdata rates make direct digitization and digital demodulation
Manuscript received July 12, 2006; revised May 28, 2007. This work was sup-ported in part by the National Institutes of Health under Grant R01 EB001032.Asterisk indicates corresponding author.
W. Xu was with the Department of Systems and Industrial Engineering, TheUniversity of Arizona, Tucson, AZ 85716 USA. He is now with the High Per-formance Analog Division, Texas Instruments, Tucson, AZ 85706 USA (e-mail:[email protected]).
D. L. Mathine is with the the College of Optical Sciences and the Electricaland Computer Engineering Department, The University of Arizona, Tucson, AZ85721 USA (e-mail: [email protected]).
*J. K. Barton is with the the Division of Biomedical Engineering, Electricaland Computer Engineering, and the College of Optical Sciences, 1657 EastHelen Street, The University of Arizona, Tucson, AZ 85721 USA (e-mail:[email protected]).
Digital Object Identifier 10.1109/TBME.2007.905402
difficult. Analog CMOS technology offers the advantagesof low recurring cost, small size, and single chip integrationfor parallel channel acquisition. Previous CMOS designs forOCT system detection and processing have been reported byKariya [5], Bourquin [6], and Egan [7]. Kariya [5] reported asingle-channel analog CMOS circuit (with separate detector)that included phase locked loop, mixer and low-pass filter(LPF) for demodulation. Images of onion were obtained atapproximately 7000 pixels/second with a reported sensitivityof dB. Bourquin [6] reported a 58 58 2-D smart detectorarray on an 8.5 8.5 mm chip area for parallel OCT signaldetection and demodulation. This chip enabled very rapidimage acquisition, up to approximately 600 000 pixels/secondwith a sensitivity of dB. Egan [7] reported a full-fieldOCT system using a CMOS camera with integrated digitalsignal processing (DSP). This system performs 2-D lateralscanning electronically by addressing the pixels of the camera.Demodulation was performed digitally using the DSP of thecamera. The speed of this system was 451 200 pixels/secondwith an unreported sensitivity.
In contrast to these previous approaches, this paper presents aunique single-channel OCT detection and demodulation designthat provides high sensitivity. By incorporating low-noise dif-ferential photoreceiver design and lock-in amplifier (LIA) baseddemodulation, this chip achieves near -dB sensitivity. Addi-tionally, the LIA- based design supplies in-phase and quadraturecomponents of the interferogram, thus enabling Doppler-basedvelocity measurements [8]. This design can be easily scaled upto 100 parallel channels on a 9.4 9.7 mm CMOS chip. Ina parallel implementation, an acquisition speed of more than700 000 pixels/second could be achieved.
II. OCT SYSTEM
The block diagram of an OCT system with the CMOS detec-tion and demodulation circuitry is shown in Fig. 1. The OCTsystem light source is a superluminescent diode (SLD) (Su-perlum Diodes, Ltd., Russia) with 890-nm center wavelengthand 90-nm full-width at half-maximum (FWHM) bandwidth.Light from the fiber-coupled source is divided by a 2 2 fibercoupler into reference and sample beams. A retroreflectingmirror mounted on a galvanometer performs 2 mm of path-length modulation in the reference arm. Light reflected from thereference mirror and backscattered from a sample are combinedby the fiber coupler and directed to the on-chip photodiode,with which the optical power is converted into photo current.Then the transimpedance amplifier (TIA) converts current intoa voltage signal, which is demodulated by a LIA with a twochannel (X, Y) chip output. Finally, the signal is sampled bythe DAQ board and displayed on the computer screen.
0018-9294/$25.00 © 2008 IEEE
486 IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. 55, NO. 2, FEBRUARY 2008
Fig. 1. OCT system block diagram. TIA: Transimpedance amplifier. LIA:Lock-in amplifier. X and Y: In-phase and quadrature components of coherencesignal harmonics. DAQ: Data acquisition board. PC: Personal computer.
The photo current at the photodiode output is givenby [2]
(1)
where and are the intensity of light backscatteredfrom the reference and sample, is the detector quantumefficiency, is the electronic charge, is the photon en-ergy, is the pathlength difference between the samplebackscatterer and the reference and is the light centerwavelength. In (1), is the combined DCsignal from reference and sample arms. The interferogramsignal is anamplitude modulated (AM) signal obtained when the referencemirror scans at a constant speed, and contains the depth-de-pendent backscattering information. The relationship betweenthe interferogram signal carrier frequency and light centerwavelength is
(2)
where is the mirror scanning speed. The relationship be-tween the interferogram signal bandwidth and the optical wave-length FWHM bandwidth is
(3)
Using (2) and (3), with our SLD source, the OCT interferogramsignal has a carrier frequency of kHz and a bandwidthof kHz. The CMOS circuit was designed to detectthis optical signal, then amplify and process the signal into aform suitable for analog to digital conversion. Digital processingis limited to logarithmic compression and conversion to imageformat.
III. CIRCUIT PRINCIPLE
A. Overview
The overall CMOS chip block diagram is shown in Fig. 2.The on-chip photodiode linearly converts the optical power inthe detection arm into photo current, then the photo current isconverted into a voltage by the TIA.
Fig. 2. Block diagram of the CMOS chip, showing the major stages of the TIA,DGS, and mixer and LPF.
The rest of the CMOS chip is a LIA [9]. The LIA has a dif-ferential gain stage (DGS) to further amplify the voltage signal.Two mixers and two LPFs are used to extract the in-phase (X)and quadrature (Y) components of the 100-kHz signal. Becausethe LPF is a switched-capacitor design, an on-chip clock cir-cuit is needed to provide the nonoverlapping clock signal [10].An external reference signal generator provides the necessarysignals at 100 kHz and 0 , 180 , 90 , and 270 phase (S1,S2, S3, and S4, respectively) for the mixers. A similar referencesignal generator has been previously described [11]. The out-puts of the chip are the X and Y components. A personal com-puter (PC) is used to digitally compute the fringe amplitude as
. Besides the X and Y output and reference signals,there are three control signals for the TIA gain, high-pass filtercorner frequency, and LPF corner frequency. Each section of thechip is described in more detail as follows.
B. Photoreceiver
The photoreceiver includes a buried double junction pho-todiode and a TIA, and has been described previously [12].Briefly, the photoreceiver has a fully differential topology, lownoise, large DC rejection capability, and a ten-fold variablegain range. The differential topology and low-noise TIA designgives the photoreceiver a high signal-to-noise ratio (SNR). TheTIA DC rejection capability serves to suppress the unwantedDC photo current , which may be ordersof magnitude greater than the interferometric signal. Thehigh-pass corner frequency and TIA gain are tunable using anexternal voltage. The RC feedback in the TIA is designed toprovide a first stage of out-of-band noise reduction. The gainvaries by less than 2% over the band of interest (95–105 kHz)and the -dB bandwidth ranges from 30 to 500 kHz.
C. Differential Gain Stage (DGS)
The DGS is used to further amplify the TIA output signal andprovide a common mode voltage required by the mixer input.The DGS employs a similar structure to the single clipping am-plifier designed by Khorram et al. [13]. However, instead ofusing NMOS, PMOS is used to construct the circuit because
XU et al.: ANALOG CMOS DESIGN FOR OPTICAL COHERENCE TOMOGRAPHY SIGNAL DETECTION AND PROCESSING 487
Fig. 3. Analog mixer block diagram.
the required mixer input common mode voltage is closer to thenegative supply voltage. A symmetrical design is used for thedifferential pairs of input and load transistors, so that the DGSgain primarily depends upon the device width to length (W/L)ratio of the transistors. The gain was designed to be approxi-mately 4.3.
D. Mixer
A LIA is created from two mixers and LPFs. The mixer shiftsthe 100-kHz modulated signal to a frequency band centeredabout DC [9]. The mixers have two differential inputs and onesingle-ended output. As shown in Fig. 2, the first mixer takescomplementary square wave pair, 100 kHz and 100 kHz
, as reference signals to extract the in-phase componentfrom the DGS output. The second mixer takes phase-shiftedcomplementary square wave pair, 100 kHz and 100 kHz
as reference signals to extract the quadrature component.The mixer circuit diagram is shown in Fig. 3. The design is
based on an analog Gilbert multiplier cell [14]. The mixer gen-erates an output current that is proportional to the multipli-cation of the input and reference signals. The output current isthen converted to a voltage using a TIA with a gain of 50-k .The overall transfer function of the mixer is
(4)
where is the input signal, is complementary referencesignal pair input. is the mixer gain determined by the Gilbertcell bias voltage , the W/L ratio of the transistors in the Gilbertmultiplier cell and the 50-k resistance.
E. Switched Capacitor LPF (SC-LPF)
Two LPFs are used to remove the sum frequency (200 kHz)of the mixer outputs while preserving the low-frequency differ-ence signal. The LPF was designed as a third-order ButterworthLPF with a 5-kHz -dB cutoff frequency and 18 dB per oc-tave slope. At this frequency range, an on-chip resistor-capac-itor filter size was estimated to be about ten times of that ofSC-LPF. In addition to smaller size, the SC-LPF has the advan-tages of high accuracy and a tunable cutoff frequency [10]. Thedesigned SC-LPF transfer function is
(5)
where , and. The transfer function of the SC-LPF has
a single pole and a pair of complex conjugate poles realized bycascading a first-order SC-LPF and a low-Q biquad design of asecond-order SC-LPF [10].
A two-phase nonoverlapping clock [10] is required by theSC-LPF to switch transistors on and off for signal filtering.The signals are made nonoverlapping to prevent short circuitsduring the switching process. In the design, a Schmitt triggerbased voltage controlled oscillator (VCO) [15] is used to pro-vide a single-phase clock, which subsequently is used to gen-erate a two-phase nonoverlapping signal by introducing a delaycircuit into a cross-coupled RS flip-flop [16]. A simple on-chipfirst-order R-C LPF is used as a delay circuit. The first-orderR-C LPF, composed of a 10-k poly-silicon resistor and a 2-pFpoly-silicon capacitor, provides a nonoverlapping time of ap-proximately 25 ns. A control voltage is used to tune the VCOfrequency, which in turn controls the CLOCK frequency and theSC-LPF cutoff frequency. The optimum VCO frequency is ap-proximately 250 kHz from simulation.
IV. MEASUREMENT
All the subcomponents were tested separately before mea-suring the performance of the OCT system. The performance ofthe photoreceiver has been reported previously [12]. The pho-toreceiver was measured to have a ten-fold gain range (250-kto 2.5-M ), input referred current noise density of 2 pA/ at100 kHz, a gain of 1.1-M , bandwidth of 500 kHz, and a greaterthan 55-dB DC rejection capability. The DGS gain was testedwith a 100 kHz sinusoidal signal input and calculated as the ratioof output to input peak to peak voltage. The measured gain of4.5 matches well to the simulated value. The measured mixergain is 14. When the CLOCK frequency was set to the simu-lated value of 250 kHz, the SC-LPF -dB cutoff frequencywas measured to be 4.5 kHz. The difference between simulatedand measured cutoff frequency was due to CMOS process vari-ations. However, because the cutoff frequency can be adjustedby the external LPF control voltage, process variations do notlimit performance. A small control voltage change moved themeasured cutoff frequency to 5 kHz. If desired for larger band-width applications, the cutoff frequency could be set as largeas 50 kHz. Fig. 4 shows the measured and simulated SC-LPFtransfer functions for a cutoff frequency of 5 kHz. The mea-sured slope is close to dB per octave as expected.
The CMOS detection and demodulation chip was integratedinto the time domain OCT system. A mirror was placed inthe sample arm and the reference mirror scanning speed wasadjusted so that the carrier frequency was 100 kHz. First, theOCT system optical output was connected to a photoreceiver(2001-FC, New Focus, San Jose, CA). The interferogram wasconverted to a voltage signal by 2001-FC, measured by anoscilloscope (Tektronix, Inc., Beaverton, OR, TDS224). Theinterferogram output was time based data, which was convertedto a depth signal through multiplication by the mirror scanningspeed. The resulting interferogram is shown as a solid line inFig. 5. Subsequently, the CMOS chip was connected to theOCT system to perform signal sensing and processing. The
488 IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. 55, NO. 2, FEBRUARY 2008
Fig. 4. Switched capacitor LPF transfer function. Diamonds: Measured datapoints. Solid line: Simulated response. Standard deviation of measured data issmaller than data point symbols.
Fig. 5. (Solid line) Measured OCT system interferogram from a mirror using acommercial photoreceiver and (dashed line) and measured envelope calculatedfrom the CMOS chip outputs.
envelope, which is shown as a dashed line in Fig. 5, was com-puted from the CMOS chip outputs as [9]. A largecenter peak with two small sidelobes appears in all signals,demonstrating that the interferogram envelope can be faithfullyextracted by the CMOS chip. The FWHM of the interferogramwas measured to be 5.6 m, whereas the FWHM of the enve-lope was 6.4 m, a 14% broadening of the interferogram, andconsequently axial resolution. This resolution degradation isprimarily due to slight attenuation of higher frequency com-ponents by the SC-LPF, and could be mitigated by increasingthe cutoff frequency. The asymmetry in both the interferogramand envelope is due to optical dispersion mismatch between thesample and reference arms of the OCT interferometer.
System sensitivity was measured by placing a 1.8 neutral den-sity filter proximal to a mirror in the sample arm, to create asample with -dB reflectivity. The signal envelope is shown
Fig. 6. Output of the CMOS circuit for a�36-dB reflector in the OCT systemsample arm.
Fig. 7. OCT images of the volar surface of finger tip showing microscope slide(MS), sweat duct (SD), stratum corneum (SC), stratum spinosum (SS), anddermis (D), taken with (a) the CMOS circuit and (b) conventional analog de-modulation circuitry.
in Fig. 6, indicating that the sensitivity is near dB. The the-oretical sensitivity can be calculated using the equation for theSNR [17]
(6)
where is the detector quantum efficiency, is the power onthe sample, is the reflectivity of the sample, is Planck’sconstant, is the optical frequency, and NEB is the noise equiv-alent bandwidth. Setting as the limit of sensitivity,and using measures values of W, and
kHz, the system could detect a sample reflectionof dB in the shot noise limit. The difference between mea-sured and theoretical sensitivity is due to electronic noise in theCMOS circuit.
An image of the volar surface of a finger tip, Fig. 7(a),was taken to qualitatively demonstrate the CMOS-based OCT
XU et al.: ANALOG CMOS DESIGN FOR OPTICAL COHERENCE TOMOGRAPHY SIGNAL DETECTION AND PROCESSING 489
system imaging quality. The finger was pressed against amicroscope slide, with index matching performed by a drop ofsaline. The image dimensions are 4 1.4 mm, 1000 1024pixels, acquisition time 52 s/pixel. Fig. 7(b) is an image offinger tip taken with the same OCT system but using conven-tional signal detection and processing components (New Focus2001 optical receiver and Stanford Research Systems SRS 810LIA). In both images, multiple sweat ducts and three skin layersare clearly visible, demonstrating excellent image quality withdepth limited to the upper dermis as is typical for OCT systemsoperating in the 800-nm wavelength range.
V. CONCLUSION
A low-cost analog CMOS circuit was demonstrated that per-forms high-quality OCT system signal detection and demodula-tion. A sensitivity of dB was achieved with low-power inci-dent on the sample, a 20-dB improvement over previously pub-lished designs. The CMOS circuit was demonstrated in our rel-atively slow, lower center frequency and small bandwidth OCTsystem. However, because the transimpedance gain and filtercutoff frequencies are adjustable with external control voltages,this CMOS chip is a flexible choice for OCT systems with centerfrequencies up to 500 kHz and bandwidths up to 50 kHz. Futureefforts will involve scale-up of the design to 100 parallel chan-nels on a 9.4 9.7 mm CMOS chip, enabling very rapid imageacquisition.
REFERENCES
[1] D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson,W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G.Fujimoto, “Optical coherence tomography,” Science, pp. 1178–1181,1991, 254(5035).
[2] B. E. Bouma and G. J. Tearney, Handbook of Optical Coherence To-mography. New York: Marcel Dekker, 2002.
[3] A. F. Fercher, W. Drexler, C. K. Hitzenberger, and T. Lasser, “Op-tical coherence tomography—principles and applications,” Rep. Progr.Phys., vol. 66, no. 2, pp. 239–303, 2003.
[4] J. M. Schmitt, “Optical coherence tomography (OCT): A review,” IEEEJ. Sel. Topics Quantum Electron., vol. 5, no. 4, pp. 1205–1215, Apr.1999.
[5] R. Kariya, D. L. Mathine, and J. K. Barton, “Analog CMOS circuitdesign and characterization for optical coherence tomography signalprocessing,” IEEE Trans. Biomed. Eng., vol. 51, no. 12, pp. 2160–2163,Dec. 2004.
[6] S. Bourquin, P. Seitz, and R. P. Salathe, “Optical coherence topographybased on a two-dimensional smart detector array,” Opt. Lett., vol. 26,no. 8, pp. 512–514, 2001.
[7] P. Egan, F. Lakestani, M. P. Whelan, and M. J. Connelly, “Full-field op-tical coherence tomography with a complimentary metal-oxide semi-conductor digital signal processor camera,” Opt. Eng., vol. 45, no. 1,pp. 015601–0, 2007.
[8] J. A. Izatt, M. D. Kulkarni, S. Yazdanfar, J. K. Barton, and A. J. Welch,“In vivo bidirectional Doppler flow imaging of picoliter blood volumesusing optical coherence tomography,” Opt. Lett., vol. 22, no. 18, pp.1439–1441, 1997.
[9] The Analog Lock-in Amplifier, Technical Note TN1002. Princeton,NJ: Princeton Applied Res. Corp., 1999.
[10] P. E. Allen and D. R. Holberg, CMOS analog circuit design, 2nd ed.New York: Oxford Univ. Press, 2002, pp. 492–600.
[11] W. Xu, G. T. Bonnema, K. W. Gossage, N. H. Wade, J. Medford, andJ. K. Barton, “Customized analog circuit design for fiber-based opticalcoherence microscopy,” Rev. Sci. Instrum., vol. 77, no. 1, p. 016104,2007.
[12] W. Xu, D. L. Mathine, and J. K. Barton, “A high-gain differentialCMOS transimpedance amplifier with on-chip buried double junctionphotodiode,” Electron. Lett., vol. 42, no. 14, pp. 803–805, 2007.
[13] S. Khorram, A. Rofougaran, and A. A. Abidi, “A CMOS limiting am-plifier and signal strength indicator,” in Proc. IEEE Symp. VLSI Cir-cuits, Tokyo, Japan, 1995, pp. 95–96.
[14] P. R. Gray, P. J. Hurst, S. H. Lewis, and R. G. Meyer, Analysis andDesign of Integrated Circuits, 4th ed. Hoboken, NJ: Wiley, 2001, pp.710–720.
[15] R. J. Baker, H. W. Li, and D. E. Boyce, CMOS Circuit Design, Layoutand Simulation. New York: IEEE Press, 1997, pp. 359–361, pp. 361.
[16] N. Weste and K. Eshraghian, Principles of CMOS VLSI Design, 2nded. Boston, MA: Addison-Wesley, 2000, pp. 348–350.
[17] E. A. Swanson, D. Huang, M. R. Hee, J. G. Fujimoto, C. P. Lin, andC. A. Puliafito, “High-speed optical coherence domain reflectometry,”Opt. Lett., vol. 17, pp. 151–153, 1992.
Wei Xu was born in Jiaojiang, Zhejiang, China. Hereceived the B.S. and M.S. degrees in electrical engi-neering from Zhejiang University in 1996 and 1999,respectively, and the Ph.D. degree in systems and in-dustrial engineering from the University of Arizona,Tucson, in 2006. His dissertation work involved thedevelopment of analog signal processing techniquesfor optical coherence imaging systems.
He is currently an analog and mixed-signal ICDesign Engineer in the High Performance Analog(HPA) Division, Texas Instruments, Tucson.
David L. Mathine (S’82–M’83) was born in Lin-coln, NE, on November 13, 1958. He received theB.S. and M.S. degrees in electrical engineering fromthe University of Nebraska, Lincoln, in 1981 and1983, respectively, and the Ph.D. degree in electricalengineering from Purdue University, West Lafayette,IN, in 1991. His thesis work involved the opticalstudy of materials by spectroscopic ellipsometry.His dissertation work involved the MBE growth andmaterial characterization of the wide gap II-VI selin-ides and tellurides as well as the III-V antimonides
and arsenides.Before receiving the Ph.D. degree, he hoined Rockwell International as a De-
vice Engineer where he aided in the development of HgCdTe IR Focal PlaneArrays integrated with silicon circuitry. From 1991 to 1996, he was a FacultyAssociate at Arizona State University, Tempe, where he was involved with theintegration ov VCSELs, MESFETs, and photodiodes with CMOS circuitry. In1996, he joined the faculty of the College of Optical Sciences, University of Ari-zona, Tucson. His current interests involve the development of a biochip for tox-icity testing of chemicals, a high-bandwidth electrooptic modulator, micropho-tonic integration with CMOS circuitry, and the development of electroopticeyeglasses.
Jennifer K. Barton (S’95–M’98) received the B.S.and M.S. degrees in electrical engineering from theUniversity of Texas at Austin and University of Cal-ifornia, Irvine, respectively, and the Ph.D. degree inbiomedical engineering from the University of Texasat Austin in 1998.
She was with McDonnell Douglas on the SpaceStation program before returning to The Universityof Texas at Austin for her Ph.D. studies. Since thattime, she has been an Assistant and Associate Pro-fessor of biomedical engineering, electrical and com-
puter engineering, and optical sciences at the University of Arizona. Her re-search interests include optical coherence imaging of tissue and laser-bloodvessel interaction.
