2021 Spie PW Sensor
2021 Spie PW Sensor
fixed-wavelength laser
Lukas Chrostowskia,b , Leanne Diasa , Matthew Mitchellb , Connor Mosqueraa , Enxiao Luana ,
Mohammed Al-Qadasia , Avineet Randhawae,f , Hassan R. Mojaverc , Eric Lyalle , Antoine
Gervaisd , Raphael Dubé-Demersd , Kashif Awanb , Steven Goub , Odile Liboiron-Ladouceurc ,
Wei Shid , Sudip Shekhara , and Karen C. Cheunge,a,f
a
Electrical and Computer Engineering, University of British Columbia, V6T 1Z4, Vancouver,
Canada
b
Stewart Blusson Quantum Matter Institute, University of British Columbia, V6T 1Z4,
Vancouver, Canada
c
McGill University, H3A 0G4, Montréal, Canada
d
Université Laval, G1V 0A6, Québec, Canada
e
School of Biomedical Engineering, University of British Columbia, V6T 1Z3, Vancouver,
Canada
f
Centre for Blood Research, University of British Columbia, V6T 1Z3, Vancouver, Canada
ABSTRACT
Commercial silicon photonic (SiP) biosensor architectures rely on expensive swept-tunable lasers that limit their
use for widespread, point-of-care applications. An alternative is the use of fixed wavelength lasers integrated
directly on a silicon photonic platform. This study investigates the design considerations of such architectures.
Keywords: biosensors, silicon photonics, point of care, evanescent field sensors
1. INTRODUCTION
Biosensors that can be used in point-of-care settings and disposable tests will play an increasingly large role, not
only in routine monitoring or screening, but also in public health. Medical diagnostic testing has taken renewed
importance in light of the COVID-19 pandemic. As governments struggle to ensure public safety without
imposing restrictions that cause economic harm, fast and accurate COVID-19 testing on a massive scale is
necessary for informed decision making. This clearly motivates the need for high-volume, low-cost diagnostic kit
production for the detection of COVID-19 and variants. However, there are numerous other applications for such
sensors, including other infectious diseases, biomarkers for autoimmune diseases such as arthritis, early cancer
detection, health and wellness monitoring, water quality monitoring, oil monitoring, etc. Accurate diagnosis may
require monitoring and testing the levels of several biomarkers, using a multiplexed sensor. Sensor arrays can
generate multidimensional data, detecting not only multiple analytes but also giving unique signatures that can
indicate disease state. A multi-antigen serology panel has been recently demonstrated by Genalyte which has
been used for research studies.1 Label-free biosensors based on evanescent-field operation are capable of such
performance. Nevertheless, the two commercial technologies, surface plasmon resonance (SPR) biosensors and
microring resonator (MRR) biosensors with swept-tunable lasers, are expensive and not amenable to low-cost,
high-volume deployment.
In this work, we propose a new biosensor technology – a resonator-based biosensor that uses a fixed-wavelength
laser, integrated within the chip. The performance of commercial MRR biosensors can be retained, while the
cost and form-factor may be reduced by orders of magnitude. This architecture overcomes the disadvantages of
prior-art MRR sensors by eliminating the swept-tunable laser and replaces the necessary precision coupling to
the silicon photonic chip with low-cost photonic wirebond integration.
Further author information: (Send correspondence to L.C.)
L.C.: E-mail: [email protected], Telephone: 1 604 822 8507
2. REVIEW OF COMMERCIAL BIOSENSOR ARCHITECTURES
Many label-free photonic biosensing platforms have been commercialized in the last two decades.2 However, the
quest to miniaturize those bulky, laboratory-use instruments to a portable form factor, and reduce the cost for
mass adoption without sacrificing the performance (sensitivity, multiplexing) is still on going. We briefly review
SPR, the gold standard for studying binding affinity and kinetics between biomolecular species, then review
silicon photonic MRR sensors.
Figure 2. Difference between SWG (top) and SWG-assist/fish-bone (bottom) waveguides, including strip-SWG taper
transitions
mechanical mirror system to focus the laser light onto a grating coupler for each sensor. While tunable lasers
have remained the standard for silicon photonic biosensors, their continued use impedes implementation of an
affordable sensing platform.
Because of the cost inefficiency of tunable lasers, some alternative approaches have been researched. One
option is to use broadband light sources, such as LEDs, SLEDs, or ASEs.9–11 While cheaper than tunable
lasers, these sources are also difficult to integrate on chip and therefore suffer from the same optical coupling
complications as lasers.
2πr × neff
λres = (1)
m
where λres is the resonant wavelength, r is the radius of the resonator, neff is the resonator effective refractive
index, and m is an integer. When the microcavity is exposed to a sample, the position of the resonant wavelength
will shift due to the change in neff . The effective interaction length of the light with the sample is characterised
by the quality factor (Q-factor), which describes how long the photon energy stays within the resonator.12
Microcavity resonators are a promising option due to their compact size, enabling high-density integration on
chip. While the sensitivity of a resonator structure cannot be improved with increasing size, various waveguide
structures can be implemented to help increase the sensitivity, and reduce the losses on-chip and increase the
Q-factor.
where ng is the group index of the resonator and Swg is waveguide mode sensitivity. For resonator sensors where
only a portion of the resonator path length acts in a sensing capacity, the waveguide mode sensitivity in Eq. 2
should be scaled by the percentage of the resonator path that is used for sensing, known as the fill factor f f .
This quantity is called the fractional sensitivity Swg−f rac = Swg · f f . The group index ng in Eq. 2 refers to the
effective refractive index of the entire resonator, which can be extracted via the free spectral range (FSR) as:
λ2
ng = (3)
L · F SR
where λ is the resonance wavelength and L is the length of the entire resonator.
The quality factor (Q) is used as a measure of how long energy stays within a resonator, which can give
a sense as to how the losses in the system affect the performance. Approximated by the ratio of the resonant
wavelength to the FWHM, the upper limit for Q is expressed as:17
2π · ng · 4.34
Q= (4)
λres · α(dB/m)
where α(dB/m) is the propagation loss within the resonator in decibels per metre.
The system Limit of Detection (LoD) is the smallest possible refractive index change which can be measured.
This is limited by the noise levels of instrumentation and environmental fluctuations, and the accuracy to which
the resonator wavelength may be determined, on the order of 1 pm, which is a small fraction of the resonator
linewidth. For easier comparison between different sensors, an alternative figure of merit is the bulk intrinsic
Limit of Detection, iLoDb , which provides a simple calculation for the minimum detectable change in the bulk
refractive index. It is defined as the index of refraction change required to shift the resonator wavelength by one
linewidth:16
λres
iLoDb = (5)
Q · Sb
A summary of sensitivity, Q-factor, and iLoDb of published silicon photonic-based sensing devices is presented
in Fig 3. This plot illustrates the design parameter trade-off between a high waveguide sensitivity (achieved by
maximizing interaction with the solution) and a high quality factor resonator (achieved by minimizing interaction
with the solution since water absorption is the dominant loss mechanism). Numerous sensor design approaches –
1) utilizing different waveguides such as strip waveguides operating in the quasi-TM mode, slot waveguides, and
This work
Figure 3. Reported silicon photonic resonator sensors performance comparison in terms of the bulk sensitivity (nm
wavelength shift per refractive index unit, RIU), the quality factor and the intrinsic limit of detection (iLoD). Except for
the design labeled at 1310, the designs operate at a wavelength of approximately 1.55 µm. The sensors include Ring-
TE-1310,13 Ring-TM-1310,13 Multi-box ring,16 Slot ring-TE,18 Substrate overetch SOE SWG,19 SWG ring-TE,20 SWG
ring-TM,21 Ring-TE,13 Thin ring-TE,22 Thin ring-TM,23 Ring-TM,23 Bragg-1310 (TM),13 Slot Bragg,24 Bragg-TE,25
Multi-box Bragg,26, 27 Disk-TE,28 Disk-TM,28 Photonic Crystal PHC-ring,29 PHC-TE,30 and SWG PHC.31
sub-wavelength grating waveguides, and 2) utilizing different resonators such as disks, rings, photonic crystals,
and Bragg gratings — have thoroughly explored this design space, illustrating that optimized designs yield a
bulk intrinsic limit of detection of approximately 5 × 10−4 RIU . The slight variations are a result of different
wavelengths, different fabrication processes (different scattering losses), and different amounts of deterministic
excess losses in the design (mode-mismatch losses, bend waveguide radiation losses). The best intrinsic limit
of detection was achieved in a straight waveguide configuration (minimizing bend loss), and operating at a
wavelength that minimizes water absorption (1.3 µm).13 The coupling coefficient to the resonator also affects
the quality factor, and the iLoDb . For example, a highly under-coupled resonator (such as the 1.3 µm TM Bragg
grating sensor13 ) will have a Q-factor that is 2× higher than a critically coupled resonator. Under-coupling is
undesirable for practical applications, however, since the reduced transmission through the resonator will reduce
the multiplexing potential due to optical power budget limited by laser power and detector sensitivity.
Figure 4. Comparison of traditional tunable laser and fixed-wavelength laser approach for a silicon photonic biosensor.
(a) The traditional approach requires a tunable laser and beam shaping and steering optics to couple light into and out
of the silicon photonic biosensor. Due to the size of the tunable laser and optics these components are off-chip. (b) By
using a fixed-wavelength laser architecture combined with photonic wire bonding, all major components can be integrated
on-chip.
loss, care should be taken to maximize the radius of curvature of the wire bond, by achieving rough alignment of
the components to be bonded in all three dimensions. However, this alignment can be performed manually. As
the DFB lasers in this project are ∼ 100 µm thick, in order to achieve a low loss photonic wire bond, we will etch
a recess into the SiP chip in which to place the laser. This also improves the thermal heat sinking of the laser
die by avoiding the buried oxide layer of the SOI wafer. As our lasers have one electrical contact on the bottom
of the die, the cavity must be metalized, as shown in Fig. 5(b). By etching a cavity with a large sidewall angle
and depositing metal via electron beam evaporation, a connection can be made to the surface of the chip for
electrical wire bonding. Alternatively, provided it is feasible to do so, an electrical bond pad could be defined in
the cavity for electrical wire bonding. Lastly, the photonic wire bond should be cladded in a UV-curable epoxy
for optimal single-mode operation, mechanical stability, and protection from the environment. Due to the close
proximity of the electrical and photonic wire bonds, this cladding material will likely need to encase both the
electrical and photonic wire bonds. Some examples of lasers that have been attached to a SiP chip are shown
in Fig. 5(c), which are proof-of-principle samples fabricated to characterise the laser attach and photonic wire
bonding process.
-20
-25
FWHM
-30
Power (dBm)
-35 ER
-40
Measured data
Lorentzian fit
-45
-50
1268.44 1268.48 1268.52 1268.56 1268.6
Wavelength (nm)
Figure 6. Resonance notch with fitted Lorentzian curve. The full-width at half-maximum (FWHM) and extinction ratio
(ER) are labelled on graph. The Q-factor is approximated to 44,345 using the FWHM = 28.6 pm.
an increased number of individually addressable locations to a sensor array. A multi-layer design, with smaller
channels near the sensor chip surface with fluidic vias to upper layers in the gasket with larger dimensions, may
be necessary to permit fan-out of the fluidic inlets and outlets for the flow-through design: inlet and outlet ports
typically comprise syringe needles with outer diameter in the range from 500 to 700 µm. The minimum practical
space from edge to edge of these fluidic interconnects would be in the range of 300 µm, especially as the needles
will be connected to tubing, while a realistic spacing would be in the range from 1 to 3 mm, thus necessitating
multi-layer gaskets for the fluidic interconnect for increasing numbers of individually addressable channels. Ad-
ditionally, the sealing footprint of the channels, to confine the different chemistries, may be a limitation as the
distance between sensors is decreased; readily achievable and robust sealing walls between channels may be on
the order of 400 µm as created using casting from 3D printed moulds, while the distance between sensors in an
array can easily be smaller.
Kirk et al. developed an inkjet approach55 for scalable, non-contact deposition of the functionalization
chemistries with high spatial precision. In this work, the microring resonators (30 µm in diameter) with ap-
proximately 200 µm centre-to-centre spacing, were successfully functionalized with printed spot precision around
5 µm. The piezoelectrically actuated inkjet dispenser can produce droplets in the range of 350 pL, and thus func-
tionalizing arrays of sensors can require only nanoliters of reagent. This contrasts favourably with the volumes
required for functionalization using flow-through microchannels, which can be in the range of tens to hundreds
of microliters.
The continuous flow microspotter system developed by Gale et al.56, 57 (Wasatch Microfluidics, now Carterra
Bio) features a network of microfluidic channels that can vertically print proteins onto a surface such as a SPR
sensor chip. Their 96-channel printhead permits simultaneous flow-based immobilization of up to 96 different
proteins. Each spot created using this continuous flow print head was a 250-µm square, and the spots are more
uniform compared to contact pin-printed spots. The continuous-flow microspotter approach compares favourably
to contact-pin and inkjet methods because the continuous-flow system permits recirculation to give high-density,
or high protein concentration, spots. The continuous flow also avoids the rapid drying that can cause protein
denaturation.
Bog et al. combined dip-pen nanolithography with a stamping approach,58 wherein a 2D array of ink spots is
first created using dip-pen nanolithography on a stamp pad to functionalize an array of whispering gallery mode
microgoblet cavities in parallel. This approach allowed the goblets, that had 100 µm center-to-center distance,
to have different functionalization chemistries.
Overall, reagent delivery into and out of biosensors has still required benchtop instrumentation59 in the
laboratory, with external pumps and valves to provide precise, controlled fluid and reagent delivery.60 Further
work will also consider the required sample preparation, and how to reduce or eliminate the need for pumps and
valves, possibly through the use of open-channel microfluidic capillary systems or digital microfluidic systems.
A truly portable biosensor will require optimization of the fluid handling, packaging, and electronics integration.
PCB
Reference
Power Supply
Sensor
Clock Generator
DSP Interfacing
Differential Compute
Laser TIA ADC
Engine I2C
SRAM
LUT
Laser and Sensor BLE
Control Circuits
Raw Curve Δ𝜆
Signal Fitting Extraction
Figure 8. Interfacing a low-cost fixed-wavelength silicon photonic sensors with CMOS electronics and external smart
devices
3.1.4 Electronics
Building the sensing electronics for an optical biosensor is dictated by the operating principle of the sensor. Fig. 8
illustrates a possible approach to interface a silicon photonic sensor with electronics and smart devices. Based
on an MRR circuit implementation, the surface or bulk interaction of the sensed substance with the exposed
sensing waveguide leads to a shift in the resonance wavelength of the ring which can be detected by the CMOS
electronics. To cancel the ambient noise and common mode drifts due to temperature or pressure variations,
another unexposed ring is used to provide a reference signal. The modulated optical signals from the sensor and
reference MRRs are guided to photodetectors (PDs). A differential trans-impedance amplifier (TIA) converts
the photocurrent to voltage which is then fed to an analog to digital converter (ADC). The bandwidth of the
TIA is a function of the modulation speed, which is typically ≤ 20 kHz, as well as the sensor’s surface binding
chemistry. The TIA must meet the gain, minimum input referred noise (IRN), and the linearity requirements
set by the subsequent stages. The TIA should provide enough gain to amplify the minimum detectable signal to
values equal or greater than the minimum least significant bit (LSB) of the ADC.
While iLoDb is optimized to improve the resolution of the detected signals, the noise contributed by the
PD, TIA and other analog front-end (AFE) circuits can also pose a limitation. The minimum overall detectable
signal of the biosensor should be above the overall noise floor at the input of the AFE. The desired current signal
is given by
∆IM DS = R∆PM DS (6)
where R and ∆PM DS are the photodetectors sensitivity to the signal’s optical wavelength and the minimum
intensity change due to the biosensors interaction with the measurands. The expression for noise at the input of
the AFE is given as:
iADC-irn
iAFE-noise = iPD-noise + iTIA-irn + (7)
ZTIA
where iPD-noise , iTIA-irn , iADC-irn and ZTIA stands for the current noise of the PDs, the input referred noise of the
TIA, the input referred noise (IRN) of the ADC and the TIA’s gain, respectivey. It can be concluded from (6)
that high transimpedance gain is desired to suppress the IRN for the upcoming stages. The noise floor can be
significantly reduced by averaging the signal over many cycles, and this averaging can be carried out digitally in
a digital signal processing (DSP) unit.
The DSP unit is also used to fit the measured spectral curve to a Lorentzian shape to extract the wavelength
shift from the Lorentzian minima. Using curve fitting relaxes the need for a highly linear AFE because the tails
of the measured curve experience less fluctuations over time which makes extracting the minima from the fitted
Lorentzian shape easier and more accurate. For such a processing scheme, an ADC of < 8 bits of quantization
can be shown to satisfy the need to detect < 1pm of wavelength shifts.
On-chip DSP is an integral part of detection in completely standalone point of care devices. However,
interfacing the biosensor chip with smart devices can enable off-loading the bulk of the DSP after transmission,
which can reduce the complexity of on-chip digital circuits. The Interfacing unit, as shown in Fig. 8, can either
use a wireline serial or a wireless Bluetooth transmission. For either case, a digital logic unit encapsulates the
data information extracted by the on-chip DSP into a serial protocol compliant data stream, which is then fed
to wireline drivers or radio-frequency (RF) circuits.
4. CONCLUSION
Since they were first commercialized by Genalyte, researchers in silicon photonic sensors have made great progress
exploring different sensor geometries and configurations, thereby improving performance metrics such as waveg-
uide sensitivity and limit of detection. Most silicon photonic sensors to date were based on passive optical chips,
where the only function implemented on-chip was evanescent field interaction with the analyte. Such designs do
not take advantage of the strengths of silicon photonics – integration. The instrumentation was implemented
off-chip using numerous costly and bulky components.
Silicon photonic circuits offer the potential of integrating all photonic and electronic functionality on a
chip. This could significantly reduce the bill of materials in sensor systems, and tilt the design trade-offs
away from the presently commercial approach of a low-cost sensor cartridge with an expensive instrument
(Fig. 4a), towards a slightly higher-cost complete-system disposable sensor (Fig. 4b). Our previous work aimed
at integrating germanium detectors on chip and solving the electrical fan-out issue;61, 62 however, the tunable
laser and the nanopositioners for coupling the optical fibres to the grating couplers remained. The work presented
in this manuscript proposes an alternative where the laser is integrated on-chip, and the tuning requirements are
transferred from the swept-tunable laser onto the silicon photonic circuit.
There remain several challenges in commercializing silicon photonic biosensors based on the presented fixed-
wavelength sensor:
The first challenge is in terms of the limit of detection. Sufficient sensitivity of silicon photonic biosensors
has been demonstrated for virus detection: previous work has successfully detected the Herpes simplex virus
(96 MDa, Young interferometer, 850 viral particles/mL)63 and bean pod mottle virus (7 MDa, Micro-Ring
Resonators, 10 ng/mL).64 However, a high sensitivity (or low limit of detection), i.e., a low false negativity, is
dependent not only on the biosensor transducer architecture but also on sample collection, sample preparation,
and the chemistry that provides the functionalization of the sensor surface.
Second, in order for sensors to be widely deployed, a high specificity, i.e., low false positivity, will be important.
This can be achieved by using a multiplexed sensor for several biomarkers that generates multidimensional data
and a unique signature for analytes. Multiplexing will contribute to confidence in the sensor result, paving the
way for wide uptake and acceptance. In this proposed approach, a single laser can power 2M sensors using a
splitter tree; the number of sensors on a chip will be limited by a) the available optical power budget (laser
power, required optical power at the detector), b) and the spacing of the sensors in the array (limited by the
functionalization chemistry printing process). While the presented design uses 24 = 16 sensors, it should be
possible to design a 256 sensor chip while meeting the above constraints. Alternatively, the sensor could use
active switching and time-division multiplexing to increase the number of sensors.
Finally, cost is a key factor contributing to wide deployment of these sensors. While the swept-tunable laser
was the most expensive component in passive-only sensor chip architectures, it can be eliminated by using a
fixed laser, which will play a significant role in lowering the cost of the biosensor. The next important cost
reduction to consider is in the microfluidics assembly. Solving these problems should enable small form-factor
sensor systems, with a tight integration of all functionality – lasers, silicon photonics, electronics, microfluidics,
and chemistry.
ACKNOWLEDGMENTS
This research was supported by the Natural Sciences and Engineering Research Council of Canada, Canada’s
Digital Technology Supercluster, and the SiEPICfab consortium, http://www.siepic.ca/fabrication. We
thank Applied Nanotools for fabricating prototype sensor chips for this work, MACOM for providing the lasers,
Hossam Shoman for design review, and Loic Laplatine and Justin Bickford for feedback and discussions.
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