Crown ether decorated silicon photonics for safeguarding against lead poisoning

Lead (Pb2+) toxification is a concerning, unaddressed global public health crisis that leads to 1 million deaths annually. Yet, public policies to address this issue have fallen short. This work harnesses the unique abilities of crown ethers, which selectively bind to specific ions. This study demonstrates the synergistic integration of highly-scalable silicon photonics, with crown ether amine conjugation via Fischer esterification in an environmentally-friendly fashion. This realizes an integrated photonic platform that enables the in-operando, highly-selective and quantitative detection of various ions. The development dispels the existing notion that Fischer esterification is restricted to organic compounds, facilitating the subsequent amine conjugation for various crown ethers. The presented platform is specifically engineered for selective Pb2+ detection, demonstrating a large dynamic detection range, and applicability to field samples. The compatibility of this platform with cost-effective manufacturing indicates the potential for pervasive implementation of the integrated photonic sensor technology to safeguard against societal Pb2+ poisoning.


Introduction
Anthropogenic lead poisoning represents one of the primary public health concerns since antiquity 1 .Pb 2+ is a cumulative toxicant that leads to multi-faceted impact on biological functions in the long term [2][3][4][5][6][7][8][9][10][11] .Pb 2+ has the affinity to substitute other bivalent and monovalent cations.For instance, Pb 2+ can replace Ca 2+ ions to cross the blood-brain barrier, resulting in neurological deficits 7 .This effect is exacerbated in children due to the ongoing development of their neurological and nervous system 8 .Pb 2+ is also found to impact cardiac function, causing reduction in the speed of heart contraction and relaxation 10 .Furthermore, fetal exposure can result in a wide array of risks during pregnancy 9 .The above examples only serve to highlight a non-exhaustive overview of the impact of lead on our society, and many other detailed studies are available to interested readers [11][12][13][14][15][16] .However, public action against lead toxification is disproportional to its impact.It has been estimated that lead service lines still deliver drinking water to about ten million households in the US alone 17 .The impact of lead leads to the common conclusion that there should be zero-tolerance to lead exposure 18 .To that effect, the Environmental and Energy Law Program (EPA), US has implemented a limit of 15 parts-per-billion (ppb) in drinking water 19 .Lead poisoning is even more pronounced in developing countries, where the World Health Organization (WHO) estimates that of the 240 million people that are overexposed, 99 % comes from developing countries 20,21 .Lead exposure accounts for more than one million deaths annually, with significant societal and economic costs, specifically in developing countries 22 .These facts highlight the urgency for the development of technologies that guards against lead toxification.
Contemporary methods for lead detection can be grouped into two primary categories: Inductively Coupled Plasma-Mass Spectrometry/Optical Emission Spectroscopy (ICP-MS/OES) 23,24 , and colorimetric test strips 25 .The former represents the state-of-art, but however, suffers from low sample throughput, requiring lengthy and expensive sample preparation and analysis by trained personnel.Furthermore, such systems are dedicated for lab use only, and not viable for on-site, in-situ analysis 24 .Colorimetric test strips, while low-cost and widely available, are qualitative and might lack accuracy in detection 25 .The development of Pb 2+ sensors presented in this work combines the advantages of both technologies: highly quantitative and selective sensing as well as rapid, portable detection capabilities.
The photonic sensor platform makes use of crown ethers, cyclic polyethers consisting of multiple oxygen atoms forming a ring structure 26,27 .This class of compounds were first synthesized by Charles Pederson in the 1960s, who was subsequently awarded the 1967 Nobel prize for this discovery 28,29 .As a result of the cavity which arises from the ring structure, crown ethers possess a remarkable ability to selectively bind to certain ions or molecules based on their properties such as size selectivity charge accommodation, ring geometry and structure energetic favorability [28][29][30] .Thus far, crown ethers have employed electrochemical [31][32][33] and fluorescent [34][35][36] -based detection schemes.However, scaling these technologies to low-cost large sensor arrays for widespread detection remains a major challenge.
In this manuscript, we demonstrated, for the first time, a crown ether functionalized silicon photonics platform.Traditionally, the functionalization of crown ether on silicon involves the use of silylating agents with trisubstituted silyl groups which are moisture and pH sensitive, and require stringent process control 37,38 .In the above protocol, the reagents can potentially undergo self-reaction, resulting in agglomeration, which decreases surface uniformity and negatively impacts sensor reproducibility 37,38 .The application of the Fischer esterification protocol 39 to couple carboxylic acid groups with the -OH group on pretreated SiO2/silicon waveguides surfaces, first demonstrated in this study, can circumvent the aforementioned problem and produce the uniform amine conjugation of crown ethers on waveguide surfaces.
We note that the successful Fischer esterification on SiO2/silicon defies the conventional view that the reaction is applicable to organics only 39 .Toward a broader scope, the Fischer esterification of an inorganic material possessing an -OH group implies the agnostic-nature of the process, indicating far-reaching technological implications to replace silylation agents in cases where they are used to couple silica/silicon with organic compounds 37,38 .For instance, different crown ethers [40][41][42][43][44][45][46][47][48][49][50] , selective to various ions (i.e., K 43 , Be 44 , Ra 46 , Cs 41 ), illustrated at the inset of Fig. 1c, can undergo amine conjugation following Fischer esterification on SiO2/Si, greatly broadening the range of applications (i.e., medical 43 , electronics manufacturing 44 , nuclear 41,46 ) that the developed platform can be extended to.As a corollary of complementary metal-oxide-semiconductor (CMOS) fabrication, SiP has proven to be a disruptive integrated photonic technology that enables high-precision mass manufacturing, without compromises in yield [51][52][53][54] .Through the synergistic integration of both technologies, the resulting platform is engineered to overcome several unaddressed issues against lead poisoning in society: 1).The successful amine conjugation of crown ethers via Fischer esterification onto aptly designed SiP circuits will enable in-situ, selective, ppb-scale detection of Pb 2+ ions, improving upon current bulky lab-based systems (ICP-MS/OES) 23,24 .2.) ICP-MS/OES requires a significant lead time from sample collection to results due to complex lab-based sample processing and analysis 23,24 .
The lightwave propagates to an asymmetric adiabatic tapered splitter 66 (Fig. 2d), where a larger proportion of the optical power is directed to the sensing path.Following, a 250 µm-long stripto-slot converter is utilized for the transition of the strip to slot optical mode 65 (Fig. 2e).With the exception of the sensing region, which is exposed to the analyte, the entire device is cladded with SiO2.The thickness of the SiO2 cladding is designated to be 2 µm to prevent interaction with the analyte, where > 99 % of the optical power is confined within the boundaries of the cladding.In the reference arm, slot waveguides with identical dimensions are also implemented.
The reason for this is to normalize waveguide propagation losses on the sensing and reference arms, and the power ratio of the asymmetrical adiabatic tapered splitters are designed according to water absorption 67 (designed losses) in the sensing region.The lightwave from the sensing and reference arms recombines at the asymmetrical adiabatic tapered splitter, forming the MZI interferometric spectrum.Power ratio of the two splitters is designed to optimize interference fringe visibility 60 (extinction ratio).The operating protocol of the sensor is elucidated in Fig. 1c.First of all, the sensing arm is exposed to deionized (DI) wafer to obtain the reference resonant wavelength (λ0); and subsequent wavelength shift will be considered in reference to this wavelength.Following, DI water will be flushed from the microfluidic chamber, and analyte possibly containing Pb 2+ ions will be added.Should the analyte contain Pb 2+ ions, a resonant shift will be induced through binding of the ions to the functionalized surface of the sensing region through surface sensing 56,[60][61][62] .However, one should also note that a proportion of the wavelength shift could also be caused by the interaction of the evanescent field with the other particles/ions/molecules in the analyte 56 .Therefore, this necessitates the subsequent flushing of the analyte from the device via the addition of DI water.This results in the retention of Pb 2+ ions, which are binded to the surface of the sensor through the functionalized layer.
Subsequently, the resonant shift (λs) measured can be attributed to the immobilized Pb 2+ ions.
The concentration of the Pb 2+ ions in the analyte can be deduced from the shift in resonance wavelength from reference (λs-λ0), utilizing a calibration curve; the calibration curve indicates wavelength shift as a function of detected concentration as shown later in Fig. 5b.We will henceforth refer to the flushing of analyte and the addition of DI water into the microfluidic chamber after ion interaction as analyte flush.Fig. 1d shows the photonic chip, with the polydimethylsiloxane (PDMS) microfluidic channel mounted via a stainless-steel fixture.Analyte input and extraction was implemented via the following inlet and outlet tubes.Optical input/output was performed via edge coupling between a lensed fiber with ~3 µm mode field diameter and a silicon coupler that tapers down to 175 nm.The abovementioned assembly (see Supplementary Note 1) was mounted on top of a thermoelectric controller (TEC), maintained at 296 K with thermal drift of lower than 2 mK.The dimensions of the slot waveguide (Strip and Slot width defined at Supplementary Note 2) were determined via eigenmode calculations in Fig. 2a-b, where H2O cladding surrounds the structure.First of all, the parameter space corresponding to the number of transverse electric (TE) modes was performed in Fig. 2a.As the top and bottom media surrounding the waveguide is asymmetrical (BOX on the bottom and H2O as the cladding), there exists a regime where the fundamental mode is not supported (in red); when the mode angle is smaller than the critical angles.Conversely, the multi-mode regime of the slot waveguide structure is indicated in blue, where the second order TE mode will be supported.According to Fig. 2a from left to right, the second order TE mode emerges when the strip and slot widths are ~260 and ~145 nm respectively.In addition, the corresponding strip width that excites the second order TE mode decreases as slot width increases.The parameter space corresponding to single TE mode propagation is highlighted in yellow.For optimization of surface sensitivity, the selection of the optimal strip and slot width, subject to the fundamental TE mode is dependent on the optical mode confinement on the surface of the sensing region.To that effect, a figure-of-merit (FoM) is defined, that takes into consideration, the optical confinement factor within 10 nm about the surface of the slot waveguides which are cladded with 20 nm of SiO2 (see Supplementary Note H2O poses significant water absorption at the C-band 67 .Yet, the length of the sensing region increases the surface sensitivity of the sensor; which forces an inherent tradeoff between the fringe visibility (extinction ratio) and sensitivity 56,[60][61][62] .The implementation of asymmetrical splitting in MZIs will serve to overcome the issue.As identical slot waveguide dimensions are implemented on the sensing and reference arms, the primary source of loss difference between the two arms comes from water absorption.It can be concluded that the splitting ratios of the MZIs must be co-designed with the length of the sensing arm, hence designed losses.The quantities are related to one another via the following equation, where the derivation is elaborated (see Supplementary Note 3).Designed losses through water absorption is assumed to be the only source of loss in the sensor.
!,  !& and  " ,  " & refers to the splitting ratios of the input and output splitter respectively.
Assuming the splitters are lossless, energy conservation dictates that  !/" = 1 −  !/" & . is the loss coefficient due to water absorption, and  refers to the length of the sensing arm.We propose a condition such that  !=  " ,  !& =  " & and  !/" ′ ≠ 0.5 (condition 1).In Fig. 2c, we plot the splitting ratios to the sensing and reference arm corresponding to maximum visibility.
A comparison to an alternate condition where arbitrary splitting is at the input splitter, and 3-dB splitting is at the output splitter (condition 2,  !& ≠ 0.5,  " & = 0.5) is also indicated in Fig. 2c; see Supplementary Note 3. In comparison, condition 1 reduces the asymmetry that is required of the splitters, alleviating fabrication requirements.As a compromise between the sensor surface sensitivity and the optical measurement setup power budget, our demonstration selected splitting ratios corresponding to sensor arm designed loss of 10 dB:  != 0.76,  " = 0.24.In regard to the selected slot waveguide dimensions in a water cladding, the waveguide propagation loss due to H2O absorption is estimated to be 35 dB/cm at λ = 1.55 μm.This gives rise to a sensing arm length of Asymmetrical adiabatic tapered splitter, which has been developed in our previous work 66 , are implemented for arbitrary power splitting.These power splitter offers the advantage of broadband operation and low loss.In Fig. 2d, we show the top-down electrical field distribution of a 30 μm-long 76/24 % power splitter.The length of the strip-to-slot converter is 250 μm, where low-loss adiabatic conversion from strip to slot mode is facilitated 65 .Similarly, the top-down electric field distribution of the lightwave as it propagates along the converter is indicated in Fig. 2e.This observation can be attributed to the functional layer consisting of more carbon compared to oxygen 70 , and the Fischer esterification of silanol with the carboxylic acid group forms O-C bonds which have a lower binding energy compared to O-Si bonds 70 .The above points to significant evidence that successful Fischer esterification have been achieved following the elucidated protocol (Fig. 3a).Furthermore, to assess the uniformity of functionalization, in Fig. 3b-d, the N 1s, C 1s and O 1s regions respectively of the XPS spectra were taken at four different points (Point 1, 2, 3, 4) on the photonic chip spaced more than 1 cm apart on the photonic chip, showing high consistency.This implies that a functional layer with good uniformity have been realized.In addition, Energy Dispersive X-ray (EDX) analysis pertaining to elemental analysis of the functional layer was performed and included in Supplementary Note 4. The results provide compelling evidence for the successful uniform functionalization of the DBTA crown ether, which contains carbon bonded to nitrogen and oxygen, via Fischer esterification and amine conjugation.

Functionalization and
Na, K, Mg, Li, Zn, Ca, Fe, Cu, Al, Sn, Cd, and Pb were chosen as highly-relevant analytes to quantify the selectivity of the photonic-based ion detection platform.The selected ions demonstrates a variety of ionic sizes and charge.Na, K, Ca, Mg, Zn and Cu are commonly found in bottled water sources 71 , while Fe, Li, and Al could be present in groundwater sources 72 .
Sn is used as a catalyst in the Fischer esterification process 68 , and Cd and Pb 73 are toxic heavy metals that should be prohibited in drinking water.Each functionalized photonic chip interacts with 100 ppb of the abovementioned analyte independently for 120 s in a microfluidic chamber.
After which, the analyte is flushed with DI water and dried with N2 gas blow.XPS is utilized to identify the elemental constitution on the surface of the photonic chips before and after ion interaction via the respective elemental binding energies of each element.Normalization was carried out where the narrow scan XPS spectra prior to ion interaction was subtracted from that after ion interaction.The normalized narrow scan XPS spectra of Na, K, Mg, Li, Zn, Ca, Fe, Cu, Al, Sn, and Cd are displayed in Fig. 4a-k respectively, indicating the absence of binding on the functionalized photonic sensor.For the abovementioned ions, we note that only Sn 2+ , which is used as the catalyst during Fischer esterification, have been identified prior to ion interaction (see Supplementary Note 5).Conventionally, Fischer esterification is favored when H2O is removed as the reaction proceeds (dehydrative esterification).However, the developed esterification process in this work utilizes H2O as a green solvent, which will decrease the catalytic activity of Brønsted acid catalysts (i.e., H2SO4) 74 .In the process (Fig. 3a), the H2Otolerant Lewis acid catalyst SnCl2, is used 68,75 where Sn is embedded into the SiO2, functioning as a heterogeneous catalyst in the process.It is known that heterogeneous catalysts show improved catalytic activity 76 that favors esterification even in the presence of H2O 77 .This is verified in Fig. 3b-d and Supplementary Fig. 4 (see Supplementary Note 4).In Fig. 4i, unmistakable binding of Pb 2+ ions is demonstrated, indicating the presence of Pb 2+ binding events on the functional layer, via identification of the Pb 4f5/2 and Pb 4f7/2 elemental binding energies 70 .Furthermore, in Supplementary Note 4, EDX analysis is performed, where the absence and presence of Pb 2+ can be clearly seen before and after interaction respectively.
From the above, it can be anticipated that the photonic sensor will be selective only towards Pb 2+ , where the ion will bind to the functionalized surface, and be present after analyte flushing.
Subsequently, the concentration of exposed Pb 2+ can be inferred from photonic surface sensing via the shift in the interferometric spectrum.understand the form of the calibration curve.The sigmoidal curve is characteristic of absorption isotherms 78,79 .As indicated by the shaded section in Fig. 5b, the wavelength shift exceeds a single FSR when the cumulative concentration of Pb 2+ is higher than ~60000 ppb.In Fig. 5c, we show a set of MZI spectra around the minima transmission points for the fringes corresponding to each of the abovementioned concentrations.As a large cumulative concentration range is presented in Fig. 5c, the spectra when cumulative Pb 2+ concentration are 0, 5 and 25 ppb are shown (Fig. 5d).A saturation of λs-λ0 against cumulative concentration is observed in Fig. 5b.This is ascribed to the saturation of the binding sites within the functional layer 78,79 .
To affirm the reproducibility of the calibration curve in Fig. 5b, three photonic sensors were tested independently, at concentrations of 80, 10 and 1 ppb.In Fig. 5e, the transmission spectra when the sensing region is exposed to DI water, DI water containing 80 ppb Pb 2+ , as well as after analyte flush of Pb 2+ are shown.Based on the positions of λs in comparison to λ0, a λs-λ0 of 2.89 nm is obtained.This shift was observed after analyte flushing, consistent with the binding mechanism on the surface of the sensor.By comparing this value to Fig. 5b, the inferred concentration from the calibration curve is 81.65 ppb, which is close to the actual value of 80 ppb.Similarly, Fig. 5f and 5g yield concentrations of 10.56 and 1.7 ppb as determined from the calibration curve, versus ground truths of 10 and 1 ppb respectively.The accuracy of the photonic measurement setup in determining the resonant wavelength of the sensor interferometric spectrum is ~20 pm, obtained from multiple spectral measurements of a sensor, at the same condition (10 ppb Pb 2+ followed by analyte flush).This indicates that the sensor is capable of detecting Pb 2+ at concentrations much lower than the EPA standard.In Fig. 4 (XPS analysis), the functional layer is found to be selective to Pb +2 ions against the other tested ions, which implies the selectivity of the photonic sensor.To further verify sensor selectivity performance at the Pb +2 safety threshold (15 ppb 19 ) Na + , K + , Mg 2+ , Ca 2+ , Fe 3+ , Cu 2+ , Sn 2+ , Cd 2+ are all tested at 15 ppb; Cd where a shift of 0.43 nm corresponding to 13.1 ppb is obtained, in reference to the calibration curve in Fig. 5b.The results in Fig. 6 and Supplementary Note 8 underpins the ability of the sensor to effectively detect Pb +2 ions in the presence of the other ions.A more comprehensive selectivity study is required, and is currently being conducted.

Conclusion
In this work, for the first time, crown ether functionalization via Fischer esterification and subsequent amine conjugation is integated with highly-scalable, and low cost inorganic SiP.
This realizes a photonic platform that enables the selective binding of Pb 2+ ions, and subsequent detection down to the ppb-scale.The novel reaction pathway proposed and demonstrated, driven via Fischer esterification defies prior expectations that the process is restricted to organics 39 .This enables the engineering of the platform to selectively detect a plethora of ions via subsequent amine conjugation of various crown ethers [40][41][42][43][44][45][46][47][48][49][50] .Furthermore, the functionalization process, by virtue of being solution-based, can be implemented at the waferscale.The reactants are dissolved in green solvents which results in minimal environmental impact.The sensor presented in this work indicates the ability to detect Pb 2+ concentrations insitu, through a wide dynamic range (1 -262000 ppb) while being highly-selective against other commonly-found, relevant ions.This work represents an encouraging step towards the ubiquitous implementation of photonic-based sensors that protects against widespread Pb 2+ poisoning.We envisage that this platform can be extended to multiplex ion detection in multiple application spheres.

Microfluidic chamber fabrication:
A custom made acrylic top enclosure, polydimethylsiloxane (PDMS) gasket and bottom mount make up the flow channel assembly (see Supplementary Note 1).This allows the sample solution and DI water to flow across the sensor on the photonic chips, and doubles as a containment to allow a fixed volume of sample solution to stay atop the sensor for 120 s during ion interaction.The custom made PDMS gasket is fabricated by curing a PDMS and photo-initiator mixture (Shin-Etsu KER-4690) in polytetrafluoroethylene (PTFE) mold under 405 nm UV lamp for 10 minutes.

Analyte preparation:
The analyte solution preparation is carried out by diluting 1000 ppm ICP standard solutions of the selected ions (Merck) with DI water to the concentration required; for low concentrations (lower than 10 ppm), multiple rounds of dilution were performed.ICP-MS is used to verify the concentrations.

Fundamental TE maintenance:
The Pb 2+ photonic sensor is designed for fundamental TE operation.Fundamental TE operation is crucial for the maintenance of interference fringes corresponding to the mode as well as fringe visibility.In order to ensure that the device is operating with only the fundamental TE mode, we utilized a chain of cascaded Multi-Mode Interferometer (MMI) structures that is optimized for the desired polarization (10 × MMI).The polarization dependent loss the TM mode experience over TE is 2 dB per MMI.Cascading 10 MMIs yields a TM against TE polarization extinction ratio of 20 dB.By optimizing the input polarization corresponding to the maximum optical power at the output, we will be able to ensure that the device operates with only the fundamental TE mode.

Measurement of the calibration curve via a cumulative approach:
The following is implemented for the measurement of the calibration curve.( !# ≠ 0.5,  " # = 0.5).Top-down electric field distribution of the d, asymmetrical adiabatic tapered splitter, and e, adiabatic strip-slot converter, where the structure of the components are outlined.optical field is intensified at the top and bottom interfaces of the waveguide (Supplementary Fig. 2f) 7 , unlike TE (Supplementary Fig. 2e), which is lateral 7 .The field at the bottom interface of the TM waveguide does not contribute to surface sensitivity.Furthermore, as the BOX has higher material refractive index than DI water, the field intensity at the bottom interface of the TM strip waveguide will be higher than that at the top (Supplementary Fig. 2f).From Supplementary Fig. 2d it can be seen that the FoM of the TM strip waveguide plateaus when strip width is larger 400 nm; the cross sectional electric field distribution of a TM strip waveguide with width of 425 nm is indicated in Supplementary Fig. 2f.Comparing the FoM of the slot waveguides (Fig. 2b of the main text) against that of the TE and TM slot waveguides, it can be seen that significantly higher surface sensitivity can be realized for slot waveguides.
To that effect, slot waveguides are implemented for the Pb 2+ photonic sensor presented in this work.
An alterna)ve MZI architecture (condi)on 2) is also illustrated in Supplementary Fig. 3b.In this design, an arbitrary and 3-dB spliDer are used at the input and output respec)vely;  !& ≠ 0.5,  " & = 0.5.The output of the MZI can be defined as the following.
Similarly, to maximize sensor visibility, we set  0C8 = 0.As such, Equa)on 3.3 can be reduced to.
Via Equa)on 3.2 and 3.4, we determine the spliPng ra)o of the arbitrary spliDers as a func)on of designed losses for the MZI architectures in Supplementary Fig. 3a-b; designed loss from water absorp)on is assumed to be the only source of op)cal loss.It can be seen that the MZI structure illustrated in Supplementary Fig. 3a reduces the asymmetrical requirement in power spliPng which significantly alleviates requirement on fabrica)on ra)os; accurate fabrica)on of highly asymmetrical power spliDers is challenging; small varia)ons in spliDer dimensions will result in significant changes from the intended design. .Furthermore, Supplementary Fig. 5 shows the XPS results of the functional layer after dilute nitric acid purification (process in Fig. 3a of the main text), prior to Sn 2+ exposure.It can be seen that presence of Sn cannot be eliminated via the purification step.We note that heterogeneous catalyst displays improved catalytic activity that favors esterification, even in the presence of H2O.Supplementary Fig. 5 also shows the XPS measurement of the functional layer after Sn 2+ exposure, followed by DI water flush and drying.As the DBTA crown ethers that undergoes amine conjugation subsequently do not bind to Sn 2+ ions, it can be seen that the XPS spectrum is similar to that prior Sn 2+ exposure.The subtraction of the narrow scan XPS spectrum before ion interaction was subtracted to that after ion interaction, referring to the normalized XPS spectrum as shown in Fig. 5 of the main text.
The fabrication of the sensor chips starts from commercially available 200 mm silicon on insulator wafers with 3 µm thick buried oxide and 220 nm thick device layer.First, the wafers are cleaned using a heated acetone bath kept at 55°C and rinsed in methanol, isopropanol and DI water.Then, an adhesion promoter (Surpass 4000) and electron-sensitive resist (ma-N 2403) are spin-coated onto the wafer and baked for 2 minutes at 90°C.The thickness of the E-beam resist after spin coating is ~300 nm (achieved at spin speeds of 3000 rounds per minute).A discharging layer (Espacer-300Z from Showa Denko Inc.) is applied to minimize charging effects.The wafer is patterned using E-beam lithography (ELS-HS50 from STS-Elionix) with

Fig. 1
Fig. 1 Concept of the Crown Ether/SiP platform for ion detection.a, 3-D illustration of the photonic Pb 2+ ion sensor based on the crown ether decorated SiP platform.The functionalization performed in the sensing arm is indicated by the features in red, where the inset illustrates the crown ether functionalized to the Si/SiO2 surface by Fischer esterification, and then amine conjugation.b, The micrograph image of the Pb 2+ ion sensor, where the sensing arm and scale bar (500 μm) are indicated.c, Elucidated operating principle of the photonic Pb 2+ ion sensor.The inset shows the exemplary applications that the ion detection platform can be extended to.d, The Pb 2+ photonic sensor assembly, consisting of the photonic chip and a microfluidic chamber.

Fig. 2
Fig. 2 Photonic design of the lead ion sensor a, Simulation of the number of supported TE optical modes in the slot waveguides as a function of strip and slot width.b, Sensor surface sensing FoM as a function of strip and slot width.c, The comparison of two proposed splitting Mach-Zehnder architectures (see Supplementary Note 3) in terms of the power asymmetry required of the splitter; condition 1 ( !=  " ,  !# =  " # ,  !/" # ≠ 0.5), condition 2 ( !# ≠ 0.5,  " # = 0.5).Top-down electric field distribution of the d, asymmetrical adiabatic tapered splitter, and e, adiabatic strip-slot converter, where the structure of the components are outlined.
FoM is performed in the parameter space of Fig 2(a) and the results are presented in Fig. 2b.The corresponding boundary condition for the number of supported TE modes (Fig. 2a) is replicated in Fig. 2b.As a guide to the eye, the highest value of FoM is indicated by region A. However, we have encountered difficulties in the selective removal of SiO2 cladding at the sensing region when the slot gap is smaller than 200 nm.As such, strip and slot width of 240 and 240 nm respectively are implemented to relax process requirements; the selected slot waveguide parameters lie close to the boundary of region A.

Characterization of 7
photonic chips before functionalization as well as, before and after interaction with different

Fig. 3
Fig. 3 The development of the Crown Ether/SiP functionalization process a, The developed crown ether/SiP functionalization process, described in 4 steps.XPS narrow spectra analysis of the b, N 1S, c, C 1S, d, O 1S regions of the photonic chips, before and after functionalization.

Fig. 6 .
Fig. 6.Selectivity performance of the Pb +2 ion photonic sensor against a, Cd 2+ , and b, K + at 15 ppb where no shifts in the interferometric spectra indicative of ion binding is observed.Similar to Fig. 5 e-g, the detection performance of the Pb 2+ photonic ion sensor is tested at 15 ppb, where significant ion binding, resulting in interferometric shifts that corresponds closely to Fig. 5b is observed.
2+ and K + are shown in Fig. 6a-b respectively.As expected from Fig. 4, no shift in the interferometric spectrum indicative of ion binding is observed.The reference interferometric spectrum (in DI water), and the resulting spectrum after exposure and analyte flush for Cd +2 and K + are presented in Fig. 6a-b respectively and data for other ions are presented in Supplementary Note 8.The data indicates no shift in the interferometric spectrum indicative of ion binding.Similar to Fig. 5e-g, the photonic sensor was tested at 15 ppb of Pb 2+ , DI water was first added to obtain the reference wavelength (λ0), and then flushed from the microfluidic chamber (Step 1).Next, DI water containing Pb 2+ was added and held for 120 s to facilitate binding of Pb 2+ to the functional surface at the sensing region (Step 2).The analyte was then removed again and DI water is added, where the resonant wavelength is measured to remove the unbound species (Step 3).The optical transmission was subsequently measured.The shift in wavelength is determined by λs-λ0.For the 6 concentrations that were measured(5, 25, 625, 2625, 62625,   262625 ppb), an additive approach was used.In Step 2, DI water containing 5, 20, 600, 2000, 60000, 200000 ppb of Pb 2+ is added sequentially as the exposed concentration is increased.The measurement was repeated six times for each set of concentrations involving each photonic sensors, as indicated by the associated error bars in Fig.5(b).

Fig. 3
Fig. 3 The development of the Crown Ether/SiP functionalization process a, The developed crown ether/SiP functionalization process, described in 4 steps.XPS narrow spectra analysis of the b, N 1S, c, C 1S, d, O 1S regions of the photonic chips, before and after functionalization.

Fig. 6 .
Fig. 6.Selectivity performance of the Pb +2 ion photonic sensor against a, Cd 2+ , and b, K + at 15 ppb where no shifts in the interferometric spectra indicative of ion binding is observed.Similar to Fig. 5 e-g, the detection performance of the Pb 2+ photonic ion sensor is tested at 15 ppb, where significant ion binding, resulting in interferometric shifts that corresponds closely to Fig. 5b is observed.
heterogeneous catalyst.Thereby, improved catalytic activity13  that favors esterification in the presence of H2O is achieved14  .Evidence of successful Fischer esterification is indicated by the XPS N 1S, C 1S, and O 1S data in Fig.3b-dof the main text respectively, and the EDX analysis in Fig S4 (See Section S4 in Supporting Information)

a
50 kV accelerating voltage and a beam current of 5 nA.After development in RD6 (Futurexx Inc.) for 80s and rinsing in DI water, the waveguides are etched using ICP-RIE (RIE-230iP from Samco Inc.) with a gas chemisty of CF4 and Ar at a pressure of 1 Pa, ICP Power of 300 W and 100 W of bias Power.The wafer is then ashed in O2 plasma to strip away any remaining E-beam resist and to remove residual fluoropolymer formed during the etching process and thoroughly cleaned in Piranha solution, followed by a DI water rinse.Subsequently, the wafer was cladded with 2 µm of SiO2 deposited at 350°C vie PECVD (Samco PD-220NL from Samco Inc).The wafer was then baked at 115 °C and silanized in an oven (TA Series from Yield Engineering Systems Inc.) to increase adhesion promotion of photoresist.Then, a thin (~1 µm) AZ 3312 photoresist layer is spin-coated and softbaked at 110°C for 60s.The sensing trench pattern is exposed into the resist using a maskless aligner (MLA-150 from Heidelberg Instruments Mikrotechnik GmbH) with a laser source centered at 405 nm.The resist was then post-exposure baked at 110 °C for 60 s and developed using AZ 726 MIF developer (Microchemicals GmbH) for 60 s.A diluted buffered oxide etchant solution was then used to open the sensing trenches, exposing the waveguides in the sensing arm.To avoid overetching, which could suspend the waveguides and generally change the structural cross-section from the intended design, the etching depth was monitored during the etching process using both