A droplet-based microfluidic platform is presented to study the nucleation kinetics of calcium oxalate monohydrate (COM), the most common constituent of kidney stones, while carefully monitoring the pseudo-polymorphic transitions. The precipitation kinetics of COM is studied as a function of supersaturation and pH as well as in the presence of inhibitors of stone formation, magnesium ions (Mg2+), and osteopontin (OPN). We rationalize the trends observed in the measured nucleation rates leveraging a solution chemistry model validated using isothermal solubility measurements. In equimolar calcium and oxalate ion concentrations with different buffer solutions, dramatically slower kinetics is observed at pH 6.0 compared to pHs 3.6 and 8.6. The addition of both Mg2+ and OPN to the solution slows down kinetics appreciably. Interestingly, complete nucleation inhibition is observed at significantly lower OPN, namely, 3.2 × 10−8 M, than Mg2+ concentrations, 0.875 × 10−4 M. The observed inhibition effect of OPN emphasizes the often-overlooked role of macromolecules on COM nucleation due to their low concentration presence in urine. Moreover, analysis of growth rates calculated from observed lag times suggests that inhibition in the presence of Mg2+ cannot be explained solely on altered supersaturation. The presented study highlights the potential of microfluidics in overcoming a major challenge in nephrolithiasis research, the overwhelming physiochemical complexity of urine.

1.
A.
Evan
,
J.
Lingeman
,
F.
Coe
, and
E.
Worcester
, “
Randall's plaque: Pathogenesis and role in calcium oxalate nephrolithiasis
,”
Kidney Int.
69
(
8
),
1313
1318
(
2006
).
2.
D. A.
Bushinsky
,
J. R.
Asplin
,
M. D.
Grynpas
,
A. P.
Evan
,
W. R.
Parker
,
K. M.
Alexander
, and
F. L.
Coe
, “
Calcium oxalate stone formation in genetic hypercalciuric stone-forming rats
,”
Kidney Int.
61
(
3
),
975
987
(
2002
).
3.
J. W.
Ridley
,
Fundamentals of the Study of Urine and Body Fluids
(
Springer
,
2018
).
4.
C.
Rose
,
A.
Parker
,
B.
Jefferson
, and
E.
Cartmell
, “
The characterization of feces and urine: A review of the literature to inform advanced treatment technology
,”
Crit. Rev. Environ. Sci. Technol.
45
(
17
),
1827
1879
(
2015
).
5.
E. M.
Worcester
and
F. L.
Coe
, “
Nephrolithiasis
,”
Prim. Care Clin. Off. Pract.
35
(
2
),
369
391
(
2008
).
6.
K.
Skorecki
,
G. M.
Chertow
,
P. A.
Marsden
,
M. W.
Taal
,
S.
Alan
, and
V.
Luyckx
,
Brenner and Rector’s The Kidney E-Book
(
Elsevier Health Sciences
,
2015
).
7.
V.
Romero
,
H.
Akpinar
, and
D. G.
Assimos
, “
Kidney stones: A global picture of prevalence, incidence, and associated risk factors
,”
Rev. Urol.
12
(
2–3
),
e86
(
2010
); available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931286/
8.
R. G.
Kalaitzidis
,
D.
Damigos
, and
K. C.
Siamopoulos
, “
Environmental and stressful factors affecting the occurrence of kidney stones and the kidney colic
,”
Int. Urol. Nephrol.
46
(
9
),
1779
1784
(
2014
).
9.
M. J.
Bono
and
W. C.
Reygaert
, “
Urinary tract infection
,” in
StatPearls
(
StatPearls Publishing
,
2018
).
10.
O. W.
Moe
, “
Kidney stones: Pathophysiology and medical management
,”
Lancet
367
(
9507
),
333
344
(
2006
).
11.
S. R.
Khan
,
M. S.
Pearle
,
W. G.
Robertson
,
G.
Gambaro
,
B. K.
Canales
,
S.
Doizi
,
O.
Traxer
, and
H.-G.
Tiselius
, “
Kidney stones
,”
Nat. Rev. Dis. Prim.
2
,
16008
(
2016
).
12.
G.
Miller
,
C.
Vermeulen
, and
J.
Moore
, “
Calcium oxalate solubility in urine: Experimental urolithiasis XIV
,”
J. Urol.
79
(
3
),
607
612
(
1958
).
13.
A. R.
Izatulina
,
V. V.
Gurzhiy
,
M. G.
Krzhizhanovskaya
,
M. A.
Kuz’mina
,
M.
Leoni
, and
O. V.
Frank-Kamenetskaya
, “
Hydrated calcium oxalates: Crystal structures, thermal stability, and phase evolution
,”
Cryst. Growth Des.
18
(
9
),
5465
5478
(
2018
).
14.
M. A.
Kelland
,
M. F.
Mady
, and
R.
Lima-Eriksen
, “
Kidney stone prevention: Dynamic testing of edible calcium oxalate scale inhibitors
,”
Cryst. Growth Des.
18
(
12
),
7441
7450
(
2018
).
15.
G.
Laffite
,
C.
Leroy
,
C.
Bonhomme
,
L.
Bonhomme-Coury
,
E.
Letavernier
,
M.
Daudon
,
V.
Frochot
,
J.-P.
Haymann
,
S.
Rouzière
,
I. T.
Lucas
,
D.
Bazin
,
F.
Babonneau
, and
A.
Abou-Hassan
, “
Calcium oxalate precipitation by diffusion using laminar microfluidics: Toward a biomimetic model of pathological microcalcifications
,”
Lab Chip
16
(
7
),
1157
1160
(
2016
).
16.
J. J.
Pahira
and
M.
Pevzner
, “
Nephrolithiasis
,” in
Penn Clinical Manual of Urology
(
Elsevier
,
2007
), pp.
235
257
.
17.
V. Y.
Bird
and
S. R.
Khan
, “
How do stones form? Is unification of theories on stone formation possible?
,”
Arch. Esp. Urol.
70
(
1
),
12
(
2017
); available at https://pubmed.ncbi.nlm.nih.gov/28221139/
18.
D. J.
Kok
and
S. E.
Papapoulos
, “
Physicochemical considerations in the development and prevention of calcium oxalate urolithiasis
,”
Bone Miner.
20
(
1
),
1
15
(
1993
).
19.
M. J.
Favus
,
M.
Zeytinoglu
, and
F. L.
Coe
, “
Idiopathic hypercalciuria and nephrolithiasis
,” in
Vitamin D
(
Elsevier
,
2018
), pp.
485
505
.
20.
V. N.
Ratkalkar
and
J. G. J.
Kleinman
, “
Mechanisms of stone formation
,”
Clin. Rev. Bone Miner. Metab.
9
(
3–4
),
187
197
(
2011
).
21.
K. P.
Aggarwal
,
S.
Narula
,
M.
Kakkar
, and
C.
Tandon
, “
Nephrolithiasis: Molecular mechanism of renal stone formation and the critical role played by modulators
,”
BioMed. Res. Int.
2013
,
1
21
(
2013
).
22.
S.
Qiu
,
A.
Wierzbicki
,
C.
Orme
,
A.
Cody
,
J.
Hoyer
,
G.
Nancollas
,
S.
Zepeda
, and
J.
De Yoreo
, “
Molecular modulation of calcium oxalate crystallization by osteopontin and citrate
,”
Proc. Natl. Acad. Sci. U.S.A.
101
(
7
),
1811
1815
(
2004
).
23.
D. T.
Denhardt
,
Osteopontin Role in Cell Signalling and Adhesion
(
Academy of Sciences
,
New York
,
1995
).
24.
J. A.
Wesson
,
R. J.
Johnson
,
M.
Mazzali
,
A. M.
Beshensky
,
S.
Stietz
,
C.
Giachelli
,
L.
Liaw
,
C. E.
Alpers
,
W. G.
Couser
,
J. G.
Kleinman
, and
J.
Hughes
, “
Osteopontin is a critical inhibitor of calcium oxalate crystal formation and retention in renal tubules
,”
J. Am. Soc. Nephrol.
14
(
1
),
139
147
(
2003
).
25.
J. A.
Molzon
, “The solubility of calcium oxalate as a function of dielectric constant,” Master’s thesis, University of Rhode Island, 1976.
26.
D. J.
Kok
,
S. E.
Papafoulos
,
L. J.
Blomen
, and
O. L.
Bijvoet
, “
Modulation of calcium oxalate monohydrate crystallization kinetics in vitro
,”
Kidney Int.
34
(
3
),
346
350
(
1988
).
27.
A. M.
Kolbach-Mandel
,
J. G.
Kleinman
, and
J. A.
Wesson
, “
Exploring calcium oxalate crystallization: A constant composition approach
,”
Urolithiasis
43
(
5
),
397
409
(
2015
).
28.
Y.
Taranets
,
O.
Bezkrovnaya
, and
I.
Pritula
, “
Crystallization kinetics of calcium oxalate monohydrate in the presence of amino acids
,”
Funct. Mater.
28
, 381–385 (
2018
).
29.
B.
Xie
,
T. J.
Halter
,
B. M.
Borah
, and
G. H.
Nancollas
, “
Aggregation of calcium phosphate and oxalate phases in the formation of renal stones
,”
Cryst. Growth Des.
15
(
1
),
204
211
(
2015
).
30.
R. P.
Sear
, “
Quantitative studies of crystal nucleation at constant supersaturation: Experimental data and models
,”
CrystEngComm
16
(
29
),
6506
6522
(
2014
).
31.
P. G.
Vekilov
, “
Nucleation
,”
Cryst. Growth Des.
10
(
12
),
5007
5019
(
2010
).
32.
D.
Gebauer
and
H.
Cölfen
, “
Prenucleation clusters and non-classical nucleation
,”
Nano Today
6
(
6
),
564
584
(
2011
).
33.
M.
Hajir
,
R.
Graf
, and
W.
Tremel
, “
Stable amorphous calcium oxalate: Synthesis and potential intermediate in biomineralization
,”
Chem. Commun.
50
(
49
),
6534
6536
(
2014
).
34.
E.
Ruiz-Agudo
,
A.
Burgos-Cara
,
C.
Ruiz-Agudo
,
A.
Ibañez-Velasco
,
H.
Cölfen
, and
C.
Rodriguez-Navarro
, “
A non-classical view on calcium oxalate precipitation and the role of citrate
,”
Nat. Commun.
8
(
1
),
1
10
(
2017
).
35.
P. J.
Smeets
,
A. R.
Finney
,
W. J.
Habraken
,
F.
Nudelman
,
H.
Friedrich
,
J.
Laven
,
J. J.
De Yoreo
,
P. M.
Rodger
, and
N. A. J. M.
Sommerdijk
, “
A classical view on nonclassical nucleation
,”
Proc. Natl. Acad. Sci. U.S.A.
114
(
38
),
E7882
E7890
(
2017
).
36.
D.
Kashchiev
, “
Classical nucleation theory approach to two-step nucleation of crystals
,”
J. Cryst. Growth
530
,
125300
(
2020
).
37.
D.
Gebauer
,
A.
Völkel
, and
H. J. S.
Cölfen
, “
Stable prenucleation calcium carbonate clusters
,”
Science
322
(
5909
),
1819
1822
(
2008
).
38.
H.
Zhai
,
L.
Wang
, and
C. V.
Putnis
, “
Inhibition of spiral growth and dissolution at the brushite (010) interface by chondroitin 4-sulfate
,”
J. Phys. Chem. B
123
(
4
),
845
851
(
2019
).
39.
W. G.
Robertson
,
M.
Peacock
, and
B. E.
Nordin
, “
Activity products in stone-forming and non-stone-forming urine
,”
Clin. Sci.
34
,
579
594
(
1968
); available at https://pubmed.ncbi.nlm.nih.gov/5666884/
40.
J.
Streit
,
L.-C.
Tran-Ho
, and
E.
Königsberger
, “
Solubility of the three calcium oxalate hydrates in sodium chloride solutions and urine-like liquors
,”
Monatsh. Chem.
129
(
12
),
1225
1236
(
1998
); available at https://link.springer.com/article/10.1007/PL00010134
41.
R. P.
Singh
, “
On the existence of NaC2O4- ion pair complex
,”
Bull. Chem. Soc. Jpn.
62
(
12
),
4089
4091
(
1989
).
42.
G. H.
Nancollas
and
G. L.
Gardner
, “
Kinetics of crystal growth of calcium oxalate monohydrate
,”
J. Crystal Growth
21
(
2
),
267
276
(
1974
).
43.
F.
Ibis
,
P.
Dhand
,
S.
Suleymanli
,
A. E. D. M.
van der Heijden
,
H. J. M.
Kramer
, and
H. B.
Eral
, “
A combined experimental and modelling study on solubility of calcium oxalate monohydrate at physiologically relevant pH and temperatures
,”
Crystals
10
(
10
),
924
(
2020
).
44.
I.
Højgaard
,
A.-M.
Fornander
,
M.-A.
Nilsson
, and
H.-G.
Tiselius
, “
The effect of pH changes on the crystallization of calcium salts in solutions with an ion composition corresponding to that in the distal tubule
,”
Urol. Res.
27
(
6
),
417
425
(
1999
).
45.
D.
Irimia
,
J.
Jose Shirley
,
A. S.
Garg
,
D. P.
Nijland
,
A. E.
van der Heijden
,
H. J.
Kramer
, and
H. B.
Eral
, “
Influence of laser parameters and experimental conditions on nonphotochemical laser-induced nucleation of glycine polymorphs
,”
Cryst. Growth Des.
21
, 631–641 (
2020
).
46.
F. M.
Penha
,
A.
Gopalan
,
J. C.
Meijlink
,
F.
Ibis
, and
H. B.
Eral
, “
Selective crystallization of d-mannitol polymorphs using surfactant self-assembly
,”
Cryst. Growth Des.
21
, 3928–3935 (
2021
).
47.
P.
Laval
,
J.-B.
Salmon
, and
M.
Joanicot
, “
A microfluidic device for investigating crystal nucleation kinetics
,”
Soft Condens. Matter
303
(
2
),
622
628
(
2007
).
48.
B.
Zheng
,
L. S.
Roach
, and
R. F.
Ismagilov
, “
Screening of protein crystallization conditions on a microfluidic chip using nanoliter-size droplets
,”
J. Am. Chem. Soc.
125
(
37
),
11170
11171
(
2003
).
49.
T.
Nisisako
,
T.
Torii
, and
T.
Higuchi
, “
Droplet formation in a microchannel network
,”
Lab Chip
2
(
1
),
24
26
(
2002
).
51.
Y.
Ai
,
R.
Xie
,
J.
Xiong
, and
Q.
Liang
, “
Microfluidics for biosynthesizing: From droplets and vesicles to artificial cells
,”
Small
16
,
11903940
(
2019
).
52.
R.
Tona
,
T. A.
McDonald
,
N.
Akhavein
,
J. D.
Larkin
, and
D.
Lai
, “
Microfluidic droplet liquid reactors for active pharmaceutical ingredient crystallization by diffusion controlled solvent extraction
,”
Lab Chip
19
, 2127–2137 (
2019
).
53.
S.
Li
,
J.
Ihli
,
W. J.
Marchant
,
M.
Zeng
,
L.
Chen
,
K.
Wehbe
,
G.
Cinque
,
O.
Cespedes
,
N.
Kapur
, and
F. C.
Meldrum
, “
Synchrotron FTIR mapping of mineralization in a microfluidic device
,”
Lab Chip
17
(
9
),
1616
1624
(
2017
).
54.
S. K.
Sia
and
G. M.
Whitesides
, “
Microfluidic devices fabricated in poly (dimethylsiloxane) for biological studies
,”
Electrophoresis
24
(
21
),
3563
3576
(
2003
).
55.
H. Z.
An
,
H. B.
Eral
,
L.
Chen
,
M. B.
Chen
, and
P. S.
Doyle
, “
Synthesis of colloidal microgels using oxygen-controlled flow lithography
,”
Soft Matter
10
(
38
),
7595
7605
(
2014
).
56.
A.
Gupta
,
A. Z. M.
Badruddoza
, and
P. S.
Doyle
, “
A general route for nanoemulsion synthesis using low-energy methods at constant temperature
,”
Langmuir
33
(
28
),
7118
7123
(
2017
).
57.
E. C.
dos Santos
,
G. M.
Maggioni
, and
M.
Mazzotti
, “
Design, statistical analysis and nucleation parameter estimation from nucleation experiments in flowing microdroplets
,”
Cryst. Growth Des.
19
(
11
),
6159
6174
(
2019
).
58.
T.
Lange
,
S.
Charton
,
T.
Bizien
,
F.
Testard
, and
F.
Malloggi
, “
OSTE+ for in situ SAXS analysis with droplet microfluidic devices
,”
Lab Chip
20
(
16
),
2990
3000
(
2020
).
59.
Z.
Hammadi
,
N.
Candoni
,
R.
Grossier
,
M.
Ildefonso
,
R.
Morin
, and
S.
Veesler
, “
Small-volume nucleation
,”
C. R. Phys.
14
(
2–3
),
192
198
(
2013
).
60.
D.
Kashchiev
,
Nucleation
(
Elsevier
,
2000
).
61.
X.
Li
,
K.
Liu
,
Y.
Pan
,
J.
Zhang
,
Q.
Lv
,
L.
Hua
,
Z.
Wang
,
J.
Li
, and
C.
Yin
, “
Roles of osteopontin gene polymorphism (rs1126616), osteopontin levels in urine and serum, and the risk of urolithiasis: A meta-analysis
,”
BioMed. Res. Int.
2015
,
315043
(
2015
).
62.
J.-y.
Qian
,
X.-j.
Li
,
Z.-x.
Gao
, and
Z.-j.
Jin
, “
Mixing efficiency and pressure drop analysis of liquid-liquid two phases flow in serpentine microchannels
,”
Processes
9
(
3
),
187
197
(
2019
).
63.
J. M.
Ottino
and
J.
Ottino
,
The Kinematics of Mixing: Stretching, Chaos, and Transport
(
Cambridge University Press
,
1989
), Vol. 3.
64.
Y. M.
Harshe
,
M. J.
van Eijk
,
C. R.
Kleijn
,
M. T.
Kreutzer
, and
P. E.
Boukany
, “
Scaling of mixing time for droplets of different sizes traveling through a serpentine microchannel
,”
RSC Adv.
6
(
101
),
98812
98815
(
2016
).
65.
S.
Jiang
and
J. H.
ter Horst
, “
Crystal nucleation rates from probability distributions of induction times
,”
Cryst. Growth Des.
11
(
1
),
256
261
(
2011
).
66.
V. V.
Vallapragada
,
G.
Inti
, and
J. S.
Ramulu
, “
A validated inductively coupled plasma-optical emission spectrometry (ICP-OES) method to estimate free calcium and phosphorus in in vitro phosphate binding study of eliphos tablets
,”
Am. J. Anal. Chem.
2
(
06
),
718
(
2011
).
67.
D.
Green
,
M.
Cooper
,
C.
German
, and
P.
Wilson
, “
Optimization of an inductively coupled plasma-optical emission spectrometry method for the rapid determination of high-precision Mg/Ca and Sr/Ca in foraminiferal calcite
,”
Geochem. Geophys. Geosyst.
4
(
6
),
8404
, https://doi.org/10.1029/2002GC000488 (
2003
).
68.
See https://www.sigmaaldrich.com/life-science/core-bioreagents/ for Biological-buffers/learning-center/buffer-reference-center.html, Sigma-Aldrich.
69.
See http://microscopy.berkeley.edu/Resources/instruction/buffers.html for Buffers, Plant Microtechnique and Microscopy.
70.
W.
Robertson
, “
Diet and calcium stones
,”
Miner. Electrolyte Metab.
13
(
4
),
228
234
(
1987
); available at https://pubmed.ncbi.nlm.nih.gov/3306314/
71.
I. J. C.
Dela Cruz
,
J. V.
Perez
,
B. G.
Alamani
,
G.
Capellades
, and
A. S.
Myerson
, “
Influence of volume on the nucleation of model organic molecular crystals through an induction time approach
,”
Cryst. Growth Des.
21
(
5
),
2932
2941
(
2021
).
72.
J.
Manissorn
,
K.
Fong-ngern
,
P.
Peerapen
, and
V.
Thongboonkerd
, “
Systematic evaluation for effects of urine pH on calcium oxalate crystallization, crystal-cell adhesion and internalization into renal tubular cells
,”
Sci. Rep.
7
(
1
),
1
11
(
2017
).
73.
H.
Tiselius
, “
The effect of pH on the urinary inhibition of calcium oxalate crystal growth
,”
Br. J. Urol.
53
(
5
),
470
474
(
1981
).
74.
C. A.
Wagner
and
N.
Mohebbi
, “
Urinary pH and stone formation
,”
J. Nephrol.
23
(
16
),
S165
S169
(
2010
); available at https://www.zora.uzh.ch/id/eprint/45805/
75.
M.
Carvalho
, “
Urinary pH in calcium oxalate stone formers: Does it matter?
,”
J. Brasil Nefrol.
40
, 6–7 (
2018
).
76.
L.
Addadi
and
S.
Weiner
, “
Interactions between acidic proteins and crystals: Stereochemical requirements in biomineralization
,”
Proc. Natl. Acad. Sci. U.S.A.
82
(
12
),
4110
4114
(
1985
).
77.
J. R.
Hoyer
,
L.
Otvos
, Jr.
, and
L.
Urge
, “
Osteopontin in urinary stone formation a
,”
Ann. N. Y. Acad. Sci.
760
(
1
),
257
265
(
1995
).
78.
L.
Fisher
,
D.
Torchia
,
B.
Fohr
,
M.
Young
, and
N. S.
Fedarko
, “
Flexible structures of SIBLING proteins, bone sialoprotein, and osteopontin
,”
Biochem. Biophys. Res. Commun.
280
(
2
),
460
465
(
2001
).
79.
H.
Tsuji
,
U.
Tohru
,
U.
Hirotsugu
,
I.
Masanori
,
H.
Yuji
, and
K.
Takashi
, “
Urinary concentration of osteopontin and association with urinary supersaturation and crystal formation
,”
Int. J. Urol.
14
(
7
),
630
634
(
2007
).
80.
L.
Keshavarz
,
R. R.
Steendam
,
M. A.
Blijlevens
,
M.
Pishnamazi
, and
P. J.
Frawley
, “
Influence of impurities on the solubility, nucleation, crystallization, and compressibility of paracetamol
,”
Cryst. Growth Des.
19
(
7
),
4193
4201
(
2019
).
81.
R.
Kacker
,
S.
Dhingra
,
D.
Irimia
,
M. K.
Ghatkesar
,
A.
Stankiewicz
,
H. J. M.
Kramer
, and
H. B.
Eral
, “
Multiparameter investigation of laser-induced nucleation of supersaturated aqueous KCl solutions
,”
Crystal Growth Des.
18
(
1
),
312
317
(
2018
).
82.
D.
Duft
and
T.
Leisner
, “
Laboratory evidence for volume-dominated nucleation of ice in supercooled water microdroplets
,”
Atmos. Chem. Phys.
4
(
7
),
1997
2000
(
2004
).
83.
F. P.
Bretherton
, “
The motion of long bubbles in tubes
,”
J. Fluid Mech.
10
(
2
),
166
188
(
1961
).
84.
C. M.
Roelands
,
J. H.
ter Horst
,
H. J.
Kramer
, and
P. J.
Jansens
, “
Analysis of nucleation rate measurements in precipitation processes
,”
Cryst. Growth Des.
6
(
6
),
1380
1392
(
2006
).
85.
Y.-C.
Hsu
,
Y.-H.
Lin
, and
L.-D.
Shiau
, “
Effects of various inhibitors on the nucleation of calcium oxalate in synthetic urine
,”
Crystals
10
(
4
),
333
(
2020
).
86.
A.
Lewis
,
M.
Seckler
,
H.
Kramer
, and
G.
Van Rosmalen
,
Industrial Crystallization Fundamentals and Applications
(
Cambridge University Press
,
2015
).
87.
V. R.
Kodati
,
G. E.
Tomasi
,
J. L.
Turumin
, and
A. T.
Tu
, “
Raman spectroscopic identification of calcium-oxalate-type kidney stone
,”
Appl. Spectrosc.
44
(
8
),
1408
1411
(
1990
).
88.
C.
Frausto-Reyes
,
S.
Loza-Cornejo
,
T.
Terrazas
,
M.
de la Luz Miranda-Beltrán
,
X.
Aparicio-Fernández
,
B. M.
López-Macías
,
S. E.
Morales-Martínez
, and
M.
Ortiz-Morales
, “
Raman spectroscopy study of calcium oxalate extracted from cacti stems
,”
Appl. Spectrosc.
68
(
11
),
1260
1265
(
2014
).
89.
V.
Castiglione
,
P.-Y.
Sacre
,
E.
Cavalier
,
P.
Hubert
,
R.
Gadisseur
, and
E.
Ziemons
, “
Raman chemical imaging, a new tool in kidney stone structure analysis: Case-study and comparison to Fourier transform infrared spectroscopy
,”
PLoS ONE
13
(
8
),
e0201460
(
2018
).
90.
M.
Orlando
,
L.
Kuplich
,
D.
de Souza
,
H.
Belich
,
J.
Depianti
,
C.
Orlando
,
E.
Medeiros
,
P.
da Cruz
,
L.
Martinez
, and
H.
Corrêa
, “
Study of calcium oxalate monohydrate of kidney stones by x-ray diffraction
,”
Powder Diffr.
23
(
S1
),
S59
S64
(
2008
).

Supplementary Material

You do not currently have access to this content.