US 11,507,135 B2

Sheet 18 of 31

Nov. 22, 2022

U.S. Patent

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US 11,507,135 B2

15

In an embodiment, a process for reading data from or
writing data to macromolecule 210 with molecular scrivener
200 includes: receiving macromolecule 210 in nanopore 280
at third shielding electrode 2148; electrostatically shielding
first writing electrode 212B and second writing electrode
212C with third shielding electrode 214B and first shielding
electrode 214A; communicating, in nanopore 280, macro-
molecule 210 from third shielding electrode 214B to
between first writing electrode 212B and second writing
electrode 212C; sequentially receiving, in nanopore 280
between first writing electrode 214 and second writing
electrode 218, individual moieties of macromolecule 210;
communicating macromolecule 210 from first writing elec-
trode 212B and second writing electrode 212C to scrivener
electrode 212A through nanopore 280 in first shielding
electrode 214A; shielding scrivener electrode 212 by first
shielding electrode 214A and second shielding electrode
218; receiving, in nanopore 280 at scrivener electrode 212,
individual moieties of macromolecule, so that third potential
V3 of scrivener electrode 212 responds to individual moi-
eties in macromolecule 210 by: electrically floating, in an
absence of charged moiety 224 or dipolar moiety 225 of
macromolecule 210, scrivener electrode 212A at third poten-
tial V3 such that third potential V3 is intermediate between
first potential V1 and second potential V2; changing, in a
presence of charged moiety 224 of macromolecule 210, third
potential V3 from the intermediate potential to electrically
read presence of charged moiety 224; and changing, in a
presence of dipolar moiety 225 of macromolecule 210, third
potential V3 from the intermediate potential to electrically
read the presence of dipolar moiety 225; communicating
macromolecule 210 from nanopore 280 at scrivener elec-
trode 212A to nanopore 280 at second shielding electrode
218; and communicating macromolecule 210 from nanopore
280 at second shielding electrode 218 to expel macromol-
ecule 210 from nanopore 280.

The process can include, when sequentially receiving, in
nanopore 280 between first writing electrode 212B and
second writing electrode 212C, individual moieties of mac-
romolecule 210: producing, by first writing electrode 212B
and second writing electrode 212C, a writing potential by:
receiving, by first writing electrode 212B, fourth potential
V4; and receiving, by second writing electrode 212C, fifth
potential V5, wherein the writing potential is a potential
difference between fourth potential V4 and fifth potential
V5; subjecting a first moiety of macromolecule 210 to the
writing potential; changing a charge of the first moiety of
macromolecule 210 in response to the writing potential;
communicating the first moiety from first writing electrode

212B and second writing electrode 212C to scrivener elec- 5

trode 212A; and changing third potential V3 of scrivener
electrode 212A to detect the first moiety by scrivener
electrode 212A if the first moiety, after changing the charge
of the first moiety by the writing potential, is charged or

dipolar. It is contemplated that, in the process for reading s

data from or writing data to macromolecule 210 with
lar scrivener 200, macromolecule 210 is subjected to
a illy-encoded pulsed voltage from writing electrodes
(212A, 212B).

The process for writing or encoding information (charges)
into molecule can further include the use of chemical
reactions that are activated by the writing potential of
writing electrodes 212A and 212B. It is contemplated that,
in the process for stabilizing the encoded macromolecule
210, the moiety that is altered by the writing electrodes will
be fixed by an activated chemical reaction rendering the
moiety inactive for further reactions.

20

&

&

16

In reading moieties in macromolecule 210, with reference
to FIG. 29, charged moiety 224 of macromolecule 210 can
be initially disposed at position X0 relative to first shielding
electrode 214 (disposed at position X1), second shielding
electrode 218 (disposed at position X3), and scrivener
electrode (disposed at position X2) that are respectively at
first potential V1, second potential V2, and third potential
V3 given as scrivener voltage VS, wherein first potential V1
is greater than second potential V2 such that scrivener
voltage VS is between first potential V1 and second potential
V2, as shown in panels A, B, and C. As charge moiety 224
moves from position X0 to position X1, scrivener voltage
VS maintains its value intermediate between first potential
V1 and second potential V2. As charge moiety 224 moves
from position X1 to position X2, scrivener voltage VS
increases, and scrivener voltage VS obtains greatest mag-
nitude when charge moiety 224 is at position X2. Thereafter,
as charge moiety 224 moves from position X2 to position
X3, scrivener voltage VS decreases and approaches the
intermediate value. As charge moiety 224 moves from
position X2 and beyond, scrivener voltage VS maintains the
intermediate value.

Reading a presence of moieties in macromolecule 210 is
shown in panel A of FIG. 30 for macromolecule 210 that

5 have, e.g., covalently bonded neutral moieties 223, charge

moieties 224, and dipolar moieties 225. Here, Scrivener
voltage VS increases due to electrostatic interaction of
scrivener electrode 212 and individual moieties. It is con-
templated that neutral moieties can produce some change in
third potential V3 via weak interactions, e.g., produced by a
quadrupole moment in neutral moiety 223 as shown for
moiety M1, M3, and M4, while some neutral moieties may
not change third potential V3 as shown for moiety M2.
Greater change of third potential V3 occurs for dipolar
moieties 225 as shown for dipolar moieties D1, D2, D3, and
D4. Even greater changes in third potential V3 occur for
charged moieties 224 as shown for positive charged moieties
C1 and C2. Further, with reference to panel B of FIG. 30, a
nucleic acid macromolecule such as DNA can have a
sequence such as T-A-G-A-T-C that produce a change in
third potential V3 shown as ner voltage VS for each
nucleobase. Here, adenine, thymine, guanine have increas-
ingly larger changes in scrivener voltage, and scrivener
voltage VS produced in a presence of cytosine is close to that
for guanine. Uracil and nucleobase derivatives also produce
changes in third potential V3.

With reference to FIG. 31, panel A an initial sequence of
moieties in macromolecule 210 that are subjected to write
voltages having amplitudes shown in the waveform below
macromolecule 210, wherein moiety M2 is charged moiety
224 that is subjected to a write potential pulse P1 produced
as a potential difference between fourth potential V4 of first
writing electrode 212B and fifth potential V5 of second
writing electrode 212C. Moiety M3 is neutral moiety 223
that is subjected to write potential pulse P2, and moiety M6
is charged moiety 224 subjected to write potential pulse P3
As result of potential pulses P1, P2, P3, as shown in panel
B, moiety M2 is converted to neutral moiety 223; moiety M3
is converted to negatively charged moiety 224, and moiety
M6 is converted to neutral moiety 223. Further, each moiety
in converted macromolecule 210A in panel B is read as
shown in the graph, wherein neutral moieties produce a
substantially similar scrivener voltage VS; negatively
charged moieties produce a negative-going scrivener voltage
relative to that for neutral moieties, and positively charged.
moieties produce a positive-going scrivener voltage relative
to that for neutral moieties.



US 11,507,135 B2

7

embodiment, detector 240 includes a field effect transistor
that includes gate electrode 242 in electrical communication
with scrivener electrode 212 and that receives third potential
V3 from scrivener electrode 212. The effect transistor 240
also includes drain electrode 244 and source electrode 246
that communicate the electrical current such that an amount
of change in the electrical current is proportional to the
change in third potential received at gate electrode 242 from
scrivener electrode 212. Electrical current can be measured.
by current amplifier 248.

In an embodiment, with reference to FIG. 4, molecular
scrivener 200 includes power source 262 in electrical com-
munication with scrivener electrode 212. Power source 262
provides fourth potential V4 to scrivener electrode 212.
When moiety (223, 224, or 225) of macromolecule 210 is
received in aperture 222 of scrivener electrode 212, moiety
(223, 224, or 225) is subjected to electric field and electron
transfer occurs between moiety (223, 224, or 225) and
scrivener electrode 212 to write a bit to moiety (223, 224, or

225). That is, when neutral moiety 223 is present at scrivener 2

electrode 212, neutral moiety 223 is reduced and obtains a
negative charge to become a negatively charged moiety.
When positively charged moiety 224 is present at scrivener
electrode 212, positively charged moiety 224 receives an
electron from scrivener electrode 212 and converts into
neutral moiety 223. When dipolar moiety 225 is present at
scrivener electrode 212, dipolar moiety 225 receives elec-
tron from scrivener electrode 212 and becomes a negatively
charged moiety. In this manner, molecular scrivener 200
writes data to macromolecule 210 at a bit-level through
charge exchange with macromolecule 210

According to an embodiment, with reference to FIG. 5
and FIG. 6, molecular scrivener 200 includes first writing
electrode 212B and second writing electrode 212C inter-
posed between first shielding electrode 214 and second
shielding electrode 218. Dielectric layer 226 is interposed
between first shielding electrode 214 of second shielding
electrode 218 as well as first writing electrode 212 B and
second writing electrode 212 feet to electrically isolate
electrodes (214, 218, 212B, 212C) from one another. First
writing electrode 212B receives fourth potential V4, and
second writing electrode 212C receives fifth potential V5.
First writing electrode 212B and second writing electrode
212 C bound nanopore 280, are opposingly disposed on
‘opposite sides of nanopore 280, and change a charge of a
moiety (e.g., 223, 224, 225) in nanopore 280 between first
writing electrode 212B and second writing electrode 212C
when fourth potential V4 is different from fifth potential V5.

According to an embodiment with reference to FIG. 7.

power source 262 is electrically interposed between first 5

writing electrode 212B and second writing electrode 212C
respectively to provide fourth potential V4 and fifth poten-
tial V5.

In an embodiment, with reference to FIG, 8, molecular

scrivener 200 includes switch 252 electrically interposed s

between power source 262 and first writing electrode 212B.
Switch 254 is electrically interposed between second writing
electrode 212 C and each of power source 262 and detector
240, e.g., gate electrode 242. To write a bit to macromol-
ecule 210, switch 252 is closed to communicate fourth
voltage V4 from power source 262 to first writing electrode
212B, and switch 254 is closed between power source 262
and second writing electrode 212C to communicate fifth
voltage V5 from power source 262 to second writing elec-
trode 212C while switch 254 is open between second writing
electrode 212 C and gate electrode 242 of detector 240 to
isolate detector 240 from second writing electrode 212 C

&

&

8

and power source 262. In this configuration, power source
262 provides voltages to cause electron transfer from writing
electrodes (212B, 212C) to macromolecule 210 to write the
bit thereto. To read bits stored in macromolecule 210, switch
252 is open to isolate power source 262 from first writing
electrode 212B, and switch 254 is open to isolate power
source 262 from second writing electrode 212C while switch
254 is closed between second writing electrode 212 C and
gate electrode 242 of detector 240 to communicate third
potential V3 from second writing electrode 212 C to gate
electrode 242 of detector 240. In this configuration, power
source 262 is isolated from writing electrodes (212 B, 212
C) and detector 240 so that writing electrodes (212B, 212C)
reads bits stored in macromolecule 210.

In an embodiment, with reference to FIG. 9, FIG. 10, and
FIG. 11, molecular scrivener 200 includes third shielding
electrode 214B disposed on first writing electrode 212B and
second writing electrode 212C, which are disposed on first
shielding electrode 214A. Third shielding electrode 214B
includes an electrode aperture that bounds nanopore 280,
receives macromolecule 210, and communicates macromol-
ecule 210 to first shielding electrode 214A after passing
between first writing electrode 212B and second writing
electrode 212C, wherein first writing electrode 212B and

5 second writing electrode 212C are interposed between third

shielding electrode 214B and first shielding electrode 214A.
Third dielectric layer 226 includes an aperture that bounds
280 nanopore and is interposed between first shielding
electrode 214A and third shielding electrode 2148, first
shielding electrode 214 and each of first writing electrode
212B and second writing electrode 212C, and third shielding
electrode 214B and each of first writing electrode 212B and
second writing electrode 212C. Third dielectric layer 226
electrically insulates from one another first shielding elec-
trode 214A, third shielding electrode 214B, first writing,
electrode 212B, and second writing electrode 212C.

According to an embodiment, with reference to FIG. 12,
molecular scrivener 200 includes write power source 262 in
electrical communication with first writing electrode 212B
and second writing electrode 212C. Power source 262
provides fourth potential V4 to first writing electrode 212B
and fifth potential V5 to second writing electrode 212C.
Third shielding electrode 214B and first shielding electrode
214A can be in electrical communication to electrically
shield first writing electrode 212B and second writing elec-
trode 212C from external electric fields. Power source 236
can be referenced to first voltage V1 and provide second
voltage V2 to second shielding electrode 218, wherein first
voltage V1 can be the same or different than second voltage
V2. As a result, macromolecule 210 is subjected to selec-
tively receiving bits from first writing electrode 212B and
second writing electrode 212C in which bits are written to
moieties (e.g,, 223, 224, 225) of macromolecule 210 by
writing electrodes (212B, 212C). Further, scrivener elec-
trode 212A reads bits stored in moieties (e.g., 224, 225) of
macromolecule 210A.

In an embodiment, with reference to FIG. 13 and FIG. 14,
molecular scrivener 200 includes scrivener structure 200A,
interposed between first compartment 290 and second com-
partment 292 of container 288 in which first compartment
290 and second compartment 292 are in fluid communica-
tion via nanopore 280. In container 288, first compartment
290 bounds a supply volume that is in fluid communication
with nanopore 280 and third shielding electrode 214 and
provides macromolecule 210 disposed in first compartment
290 to nanopore 280. Second compartment 292 bounds a
receiver volume and is in fluid communication with nanop-



US 11,507,135 B2

Sheet 12 of 31

Nov. 22, 2022

U.S. Patent

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Sheet 22 of 31

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US 11,507,135 B2

17

Molecular scrivener 200 and processes disclosed herein
have numerous beneficial uses, including protein identifi
tion and quantification, DNA and protein sequencing, and
hardware for molecular computer memory. Advantageously,
molecular scrivener 200 overcomes limitations of technical
deficiencies of conventional articles such as bandwidth,
chemical selectivity, discrimination of similar objects, and
insufficient signal to noise ratio. Because the measurement
of charge is rapid and made at the nanometer-scale, the
device also overcomes inaccuracies in identifying proteins
due to diffusional broadening.

Moreover, molecular scrivener 200 and processes herein
have numerous advantageous properties. In an aspect, the
technology is scalable and can be operated in arrays.

Molecular scrivener 200 and processes herein unexpect-
edly measures charges within macromolecules at high spa-
tial resolution and at the single electron charge limit. More-
over, molecular scrivener 200 determines the location of
charged amino acid residues within a folded or denatured

protein, and thereby identify proteins based on the location 2

of charged amino acid residues within folded or denatured
proteins. In an analogy to 2D gel electrophoresis, further
discrimination of proteins by molecular scrivener 200 is
made possible by measuring the locations of charged amino
acid residues as a function of pH. The articles and processes
herein are illustrated further by the following Example,
which is non-limiting.

While one or more embodiments have been shown and
described, modifications and substitutions may be made
thereto without departing from the spirit and scope of the
invention. Accordingly, it is to be understood that the present
invention has been described by way of illustrations and not
limitation. Embodiments herein can be used independently
or can be combined.

All ranges disclosed herein are inclusive of the endpoints,
and the endpoints are independently combinable with each
other. The ranges are continuous and thus contain every
value and subset thereof in the range. Unless otherwise
stated or contextually inapplicable, all percentages, when
expressing a quantity, are weight percentages. The suflix
“(s)” as used herein is intended to include both the singular
and the plural of the term that it modifies, thereby including
at least one of that term (e.g., the colorant(s) includes at least
‘one colorants). “Optional” or “optionally” means that the
subsequently described event or circumstance can or cannot
occur, and that the description includes instances where the
event occurs and instances where it does not. As used herein,
“combination” is inclusive of blends, mixtures, alloys, reac-
tion products, and the like.

As used herein, “a combination thereof” refers to a
combination comprising at least one of the named constitu-
ents, components, compounds, or elements, optionally
together with one or more of the same class of constituents,
components, compounds, or elements.

All references are incorporated herein by reference.

The use of the terms “a” and “an” and “the” and similar
referents in the context of describing the invention (espe-
cially in the context of the following claims) are to be
construed to cover both the singular and the plural, unless
otherwise indicated herein or clearly contradicted by con-
text. “Or” means “and/or.” It should further be noted that the
terms “first,” “second,” “primary,” “secondary,” and the like
herein do not denote any order, quantity, or importance, but
rather are used to distinguish one element from another. The
modifier “about” used in connection with a quantity is
inclusive of the stated value and has the meaning dictated by
the context (e.g., it includes the degree of error associated

10

0

&

0

50

0

18

with measurement of the particular quantity). The conjune-
tion “or” is used to link objects of a list or alternatives and
is not disjunctive; rather the elements can be used separately
or can be combined together under appropriate circum-
stances

What is claimed is:

1. A molecular scrivener 200 for reading data from or
writing data to a macromolecule 210, the molecular scriv-
ener 200 comprising

a pair of shielding electrodes comprising:

a first shielding electrode 214 comprising a first trans-
mission aperture 216 bounded by the first shielding
electrode 214 and that:
receives a first potential V1; and
receives and communicates the macromolecule 210

through the first transmission aperture 216 in
presence of the first potential V1; and

a second shielding electrode 218 comprising a second
transmission aperture 220 bounded by the second
shielding electrode 218 and that:
receives a second potential V2; and
receives and communicates the macromolecule 210

through the second transmission aperture 220,
the second transmission aperture 220 being in fluid
communication with and aligned with first trans-
mission aperture 216, and
the second transmission aperture 220 being spaced
apart from the first transmission aperture 216;
a scrivener electrode 212 comprising a third transmission
aperture 222 bounded by the scrivener electrode 212
and that:
is interposed between the first shielding electrode 214
and the second shielding electrode 218;

electrically floats at a third potential V3 such that, in an
absence of a charged moiety 224 or a dipolar moiety
225 of the macromolecule 210, the third potential V3
is intermediate between the first potential V1 and the
second potential V2; and

receives the macromolecule 210 from the first shielding
electrode 214;

communicates the macromolecule 210 through the sec-
ond transmission aperture 220 to the second shield-
ing electrode 218; and

the third potential V3 changes in a presence of the
charged moiety 224 of the macromolecule 210 to
electrically read the presence of the charged moiety
224;

the third potential V3 changes in a presence of the
dipolar moiety 225 of the macromolecule 210 to
electrically read the presence of the dipolar moiety
225;

the third transmission aperture 222 being in fluid com-
munication with and aligned with first transmission
aperture 216, and

is spaced apart from the first shielding electrode 214
and the second shielding electrode 218;

a first dielectric layer 226 interposed between the first
shielding electrode 214 and the scrivener electrode 212
and that electrically isolates the first shielding electrode
214 and the scrivener electrode 212, the first dielectric
layer 226 comprising a fourth transmission aperture
228 bounded by the first dielectric layer 226 and that:
receives the macromolecule 210 from the first shielding

electrode 214; and

communicates the macromolecule 210 through the
fourth transmission aperture 228 to the scrivener
electrode 212, and



U.S. Patent Nov. 22, 2022 Sheet 3 of 31

<---

223 210

US 11,507,135 B2

200
280
l a 214
250
226 ~~ 226
212
236 LE
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a~ 218
v2 218
240
250
238

FIG. 3

248

244

246


US 11,507,135 B2

3

potential from the intermediate potential to electrically read
the presence of the dipolar moiety; communicating the
macromolecule from the nanopore at the scrivener electrode
to the nanopore at the second shielding electrode; and
communicating the macromolecule from the nanopore at the
second shielding electrode to expel the macromolecule from
the nanopore.

BRIEF DESCRIPTION OF THE DRAWINGS

The following description should not be considered lim-
iting in any way. With reference to the accompanying
drawings, like elements are numbered alike.

FIG. 1 shows: in panel A a perspective view of a molecu-
lar scrivener, in panel B a plan view of the molecular
scrivener, in panel C a cross-section along line A-A shown
in panel B, and in panel D a cross-section along line A-A
shown in panel B;

FIG. 2 shows: in panel A a perspective view of a molecu-
lar scrivener, in panel B a plan view of the molecular
scrivener, in panel C a cross-section along line A-A shown
in panel B, and in panel D a cross-section along line A-A
shown in panel B;

FIG. 3 shows a molecular scrivener for reading data in a
macromolecule;

FIG. 4 shows a molecular scrivener for writing data to a
macromolecule;

FIG. 5 shows a perspective view of'a molecular scrivener;

FIG. 6 shows in panel A a plan view of the molecular
scrivener shown in FIG. 6, in panel B a cross-section along
line A-A shown in panel A, and in panel C a cross-section
along line B-B shown in panel A;

FIG. 7 shows a molecular scrivener shown in FIG. 6 for
writing data to a macromolecule;

FIG. 8 shows a molecular scrivener for reading data in a
macromolecule and for writing data to macromolecule;

FIG. 9 shows a molecular scrivener for writing data to a
macromolecule and reading data in a macromolecule;

FIG. 10 shows an exploded view of electrodes included in
the molecular scrivener shown in FIG. 9 (dielectric material
not shown);

FIG. 11 shows in panel A a plan view of the molecular
scrivener shown in FIG. 9, in panel B a cross-section along
line A-A shown in panel A, and in panel C a cross-section
along line B-B shown in panel A;

FIG. 12 shows a molecular scrivener for writing data to a
macromolecule and reading data in a macromolecule:

FIG. 13 shows a molecular scrivener for writing data to a
macromolecule;

FIG. 14 shows a molecular scrivener for writing data to a 5

macromolecule:

FIG. 15 shows in panel A a plan view of a scrivener
electrode that includes a transmission aperture, in panel B a
cross-section along line A-A shown in panel A, in panel C

a plan view of scrivener electrodes disposed on opposing. 5

sides of a transmission aperture, in panel D a cross-section
along line A-A shown in panel C, in panel E a plan view of
ivener electrodes disposed on opposing sides of a trans-
mission aperture, in panel F a cross-section along line A-A
shown in panel E, and in panel G a cross-section along line
B-B shown in panel E:

FIG. 16 shows a plan view of a substrate and detector
involved in making a molecular scrivener in panel A, and
panel B shows a cross-section along line A-A shown in panel
A:

FIG. 17 shows a plan view of a dielectric layer formed on
the substrate and detector shown in FIG. 16 that is involved

20

&

4

65

4

in making a molecular scrivener in panel A, and panel B
shows a cross-section along line A-A shown in panel A;

FIG. 18 shows a plan view of a trench formed in the
dielectric layer and filled with the dielectric subsequent to
planarization of the dielectric layer shown in FIG. 17 that is
involved in making a molecular scrivener in panel A, and
panel B shows a cross-section along line A-A shown in panel
A:

FIG. 19 shows a plan view ofa second shielding electrode
formed on the dielectric layer shown in FIG. 18 that is
involved in making a molecular scrivener in panel A, and
panel B shows a cross-section along line A-A shown in panel
AS

FIG. 20 shows a plan view of a dielectric layer formed on
the second shielding electrode shown in FIG. 19 that is
involved in making a molecular scrivener in panel A, and
panel B shows a cross-section along line A-A shown in panel
A:

FIG. 21 shows a plan view ofa scrivener electrode formed
on the dielectric layer shown in FIG. 20 that is involved in
making a molecular scrivener in panel A, and panel B shows
a cross-section along line A-A shown in panel A;

FIG. 22 shows a plan view of a dielectric layer formed on
the scrivener electrode shown in FIG. 21 that is involved in

5 making a molecular scrivener in panel A, and panel B shows

a cross-section along line A-A shown in panel A;

FIG. 23 shows a plan view of a first shielding electrode
formed on the dielectric layer disposed on the scrivener
electrode shown in FIG. 22 that is involved in making a
molecular scrivener in panel A, and panel B shows a
cross-section along line A-A shown in panel A;

FIG. 24 shows a plan view of a via formed in the first
shielding electrode, the second shielding electrode, and
several dielectric layers shown in FIG. 23 that is involved in
making a molecular scrivener in panel A, and panel B shows
a cross-section along line A-A shown in panel A;

FIG. 25 shows a plan view of a cavity formed in the trench
by removing some of the dielectric shown in FIG. 24 that is
involved in making a molecular serivener in panel A, and
panel B shows a cross-section along line A-A shown in panel
A:

FIG. 26 shows a plan view ofa dielectric layer formed on
the first shielding electrode with a plurality of vias formed
therein that expose several of the electrodes shown in FIG.
25 that is involved in making a molecular scrivener in panel
A, and panel B shows a cross-section along line A-A shown
in panel A;

FIG. 27 shows a plan view of electrical conductors
formed in the vias of the dielectric layer shown in FIG. 26
that is involved in making a molecular scrivener in panel A,
and panel B shows a cross-section along line A-A shown in
panel

FIG. 28 shows a plan view of the nanopore formed in the
shielding electrodes, scrivener electrodes, and a portion of
the dielectric layers shown in FIG. 27 that is involved in
making a molecular scrivener in panel A, and panel B shows
a cross-section along line A-A shown in panel A;

FIG. 29 shows in panel A a position of a charged moiety
relative to electrodes in a molecular scrivener, in panel B a
graph of voltage versus position, and in panel C a graph of
the logarithm of current versus position;

FIG. 30 shows in panel A a graph of scrivener voltage
versus moiety and in panel B a graph of scrivener voltage
versus base number; and

FIG. 31 shows in panel A a graph of potential difference
versus moiety and in panel B a graph of scrivener voltage
versus moiety.



US 11,507,135 B2

Sheet 19 of 31

Nov. 22, 2022

U.S. Patent

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US 11,507,135 B2

5
DETAILED DESCRIPTION.

A detailed description of one or more embodiments is
presented herein by way of exemplification and not limita-
tion.

It has been discovered that a molecular scrivener herein
provides digital storage of digital data on a macromolecule
such as a nucleic acid, polymer, and the like. The molecular
scrivener encodes in the macromolecule such as a static
polymer (¢.g., DNA or other collection of nucleobases) or an
active polymer, e.g., a redox-switchable polymer. Advanta-
geously and unexpectedly, the molecular scrivener writes
data (also referred to as storing information) in a molecular
volume or electrostatic dipole of a moiety in a macromol-
ecule and can selectively write data to a bit, i.e., a smallest
feature size of the macromolecule. Beneficially, the molecu-
lar scrivener writes data to the macromolecule so that, e.g.,
greater than 10° bits can be stored in the macromolecule. It
is contemplated that a storage chip that includes 10° scriv-
ener cells can store greater than 10'* bits. Additionally, the
molecular scrivener reads data from the macromolecule as
an electrostatic potential, e.g., of different functional groups,
with atomic resolution and writes data to switchable poly-
mers with precision and speed.

In view of an exponential increase of digitally stored data
that is approaching limits of conventional storage media, the
molecular scrivener provides long-term storage of seldom-
used data for archiving data and often-used data for active
archiving with low cost, high capacity, and reliable long-
term storage in macromolecules. The molecular scrivener
overcomes technological problems with writing data stati-
cally through synthetic chemistry and also provides practi-
cal, dynamic digital storage. Further, to incorporate the
molecular scrivener into computing systems, the molecular
scrivener can be integrated on a semiconductor chip. Ben-
eficially, the molecular scrivener includes solid-state mate-
rials rather than solely biological materials.

In an embodiment, with reference to FIG, 1, molecular
scrivener 200 writes data to or reads data from macromol-
ecule 210. Molecular scrivener 200 includes a pair of
shielding electrodes that includes first shielding electrode
214 and second shielding electrode 218. First shielding
electrode 214 includes first transmission aperture 216
bounded by first shielding electrode 214, receives first
potential V1, and receives and communicates macromol-
ecule 210 through first transmission aperture 216 in presence
of first potential V1. Second shielding electrode 218
includes second transmission aperture 220 bounded by sec-
ond shielding electrode 218, receives second potential V2,

and receives and communicates macromolecule 210 through 5

second transmission aperture 220. Second transmission
aperture 220 is in fluid communication with and aligned
with first transmission aperture 216. Here, second transmis-
sion aperture 220 is spaced apart from first transmission

aperture 216. Scrivener electrode 212 is interposed between

first shielding electrode 214 and second shielding electrode
218, includes third transmission aperture 222 bounded by
scrivener electrode 212, receives macromolecule 210 from
first shielding electrode 214, and communicates macromol-
ecule 210 through second transmission aperture 220 to
second shielding electrode 218. Moreover, scrivener elec-
trode 212 electrically floats at third potential V3 such that,
in an absence of charged moiety 224 or dipolar moiety 225
of macromolecule 210, third potential V3 is intermediate
between first potential V1 and second potential V2. Third
potential V3 changes in a presence of charged moiety 224 of
the macromolecule 210 to electrically read the presence of

20

&

&

6

the charged moiety 224, and third potential V3 changes in a
presence of dipolar moiety 225 of macromolecule 210 to
electrically read the presence of dipolar moiety 225. Addi-
tionally, third transmission aperture 222 is in fluid commu-
nication with and aligned with first transmission aperture
216 and is spaced apart from first shielding electrode 214
and second shielding electrode 218. In molecular scrivener
200, first dielectric layer 226 is interposed between first
shielding electrode 214 and scrivener electrode 212 to
electrically isolate first shielding electrode 214 and scrivener
electrode 212, First dielectric layer 226 includes fourth
transmission aperture 228 that is bounded by first dielectric
layer 226, receives macromolecule 210 from first shielding
electrode 214, and communicates macromolecule 210
through fourth transmission aperture 228 to scrivener elec-
trode 212. Fourth transmission aperture 228 is in fluid
communication with and aligned with first transmission
aperture 216. Similarly, second dielectric layer 230 is inter-
posed between scrivener electrode 212 and second shielding
electrode 218 to electrically isolate second shielding elec-
trode 218 and scrivener electrode 212, wherein second
dielectric layer 230 includes fifth transmission aperture 232
bounded by second dielectric layer 230 and that receives
macromolecule 210 from scrivener electrode 212 and com-

5 municates macromolecule 210 through fifth transmission

aperture 232 to second shielding electrode 218. Fifth trans-
ion aperture 232 is in fluid communication with and
aligned with first transmission aperture 216. Molecular
scrivener 200 also includes nanopore 280 that includes
transmission apertures (216, 218, 222, 232, 220). In this
configuration, molecular scrivener 200 receives macromol-
ecule 210 in nanopore 280 at first shielding electrode 214,
communicates macromolecule 210 through nanopore 280
such that individual moieties (e.g., 223, 224, 225) or incident
at scrivener electrode 212. Scrivener electrode 212 detect the
presence of charged moiety 224 and dipolar moiety 225 by
changing third potential V3 in presence of charged moiety
224 or dipolar moiety 225 of macromolecule 210.

Electrodes (e.g., 212, 214, 218) can be various sizes and
shapes such as completely covering dielectric layer 226 with
first shielding electrode 214 as shown in FIG. 1 or partially
covering dielectric layer 226 with first shielding electrode
214 as shown in FIG. 2.

In an embodiment, with reference to FIG. 3, molecular
scrivener 200 includes first power source 236 in electrical
communication with first shielding electrode 214 and that
provides first potential V1 to first shielding electrode 214
such that first shielding electrode 214 electrostatically
shields scrivener electrode 212 from electrostatic interaction
with an electric field exterior to nanopore 280. Second
power source 238 is in electrical communication with first
power source 236 and second shielding electrode 218 and
provides second potential V2 to second shielding electrode
218 such that second shielding electrode 218 electrostati-
cally shields scrivener electrode 212 from electrostatic inter-
action with electric fields exterior to nanopore 280. Here,
first power source 236 receives second potential V2 from
second power source 238 and provides first potential V1
referenced to second potential V2. Electrical connections
can be made by electrical conductor 250 that can be, e.g...
wire.

Detector 240 is in electrical communication with scriv-
ener electrode 212 and receives third potential V3 from
scrivener electrode 212 and produces an electrical signal. It
is contemplated that a change in electrical current in the
electrical signal is proportional to the change in third poten-
tial V3 from scrivener electrode 212. According to an



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US011507135B2

a2) United States Patent (0) Patent No: US 11,507,135 B2
Cheung et al. (45) Date of Patent: Nov. 22, 2022
(54) MOLECULAR SCRIVENER FOR READING (56) References Cited
OR WRITING DATA TO A
MACROMOLECULE U.S. PATENT DOCUMENTS
(71) Applicant: Government of the United States of 2014/0174927 AL* 6/2014 Bashir ..... we € RQ a eas
America, as represented by the 204/603
* Ta 2019/0004029 AL* 1/2019 Branton BOID 71/74
Secretary of Commerce, Gaithersburg, 2019/0383788 AI* 12/2019 Predki C12Q 116869

MD (US)

(72) Inventors: Kin P Cheung, Rockville, MD (US); FOREIGN PATENT DOCUMENTS
Joseph W Robertson, Washington, DC gp 3325092 Al 102018
(US); John J Kasianowicz,
Darnestown, MD (US) OTHER PUBLICATIONS

(73) Assignee: GOVERNMENT OF THE UNITED
STATES OF AMERICA, AS
REPRESENTED BY THE
SECRETARY OF COMMERCE, (Continued)
Gaithersburg, MD (US)

Schneider, G.,etal., “DNA Translocation through Graphene Nanopor
Nano Letters, 2010, p. 3163-3167, vol. 10.

Primary Examiner — Xiaochun L Chen
(*) Notice: Subject to any disclaimer, the term of this (74) Attorney, Agent, or Firm — Office of Chief Counsel
patent is extended or adjusted under 35 for National Institute of Standards and Technology
U.S.C. 154(b) by 891 days.
(57) ABSTRACT
A molecular scrivener reads data from or writes data to a
macromolecule and includes: a pair of shielding electrodes;
a scrivener electrode between the first and second shielding

(21) Appl. No.: 16/383,707
(22) Filed: Apr. 15, 2019

(65) Prior Publication Data electrodes and that electrically floats at a third potential that,
in an absence of a charged or dipolar moiety of the macro-
US 2020/0326748 Al Oct. 15, 2020 molecule, is intermediate between the first and second

potentials and changes in a presence of the charged or

(51) Int. Cl. dipolar moiety; a dielectric layer interposed between shield-
GHC 13/00 (2006.01) ing electrodes and the scrivener electrode; and a nanopore
GOGF 1/16 (2006.01) that communicates the macromolecule through the elec-
B82Y 35/00 (2011.01) trodes and dielectric layers. Reading data from or writing

(52) US. Cl. data to a macromolecule includes: sequentially receiving, at
Pc GO6F 1/1613 (2013.01); B82Y 35/00 the scrivener electrode, individual moieties of the macro-

(2013.01), GIIC 13/0016 (2013.01); GIIC_ molecule so that the third potential responds to individual
13/0019 (2013.01) moieties; communicating the macromolecule from the scriv-
(58) Field of Classification Search ener electrode to the second shielding electrode and from
CPC ... GOGF 1/1613; B82Y 35/00; G1IC 13/0016; second shielding electrode to expel the macromolecule from
GIIC 13/0019; G1IC 13/004; GIIC the nanopore.
13/0069
See application file for complete search history. 20 Claims, 31 Drawing Sheets



U.S. Patent Nov. 22, 2022 Sheet 10 of 31 US 11,507,135 B2



US 11,507,135 B2

Sheet 9 of 31

Nov. 22, 2022

U.S. Patent

212B

FIG. 9


US 11,507,135 B2

21

communicate the macromolecule from the first com-
partment to the nanopore; and

a second control electrode disposed in the second
compartment and that imparts the transmissive force
in the nanopore to communicate the macromolecule
from the nanopore to the second compartment.

10. The molecular scrivener 200 of claim 6, wherein the
scrivener electrode 212, the first writing electrode, and the
second writing electrode independently comprise an atomi-
cally-thin electrically conductive membrane or a metal.

11. The molecular scrivener 200 of claim 10, wherein the
atomically thin electrically conductive membrane comprises
graphene.

12. The molecular scrivener 200 of claim 10, wherein a
thickness of the first shielding electrode, the second shield-
ing electrode 218, the third shielding electrode, the first
writing electrode, the second writing electrode, the first
dielectric layer, the second dielectric layer, and the third
dielectric layer independently is from 3.4 A to 3 nm.

13. The molecular scrivener 200 of claim 1, wherein the
macromolecule comprises a plurality of nucleic acid bases,
a polymer comprising a plurality of charge moieties or
dipolar moieties disposed along a backbone of the polymer,
or a combination comprising a combination of the nucleic
acid bases and the polymer.

14. A process for reading data from or writing data to a
macromolecule with the molecular scrivener of claim 1, the
process comprising:

receiving the macromolecule in the nanopore at the first

shielding electrode, the macromolecule comprising a
plurality of moieties, wherein the moieties comprise a
neutral moiety, a charged moiety, a dipolar moiety, or
acombination comprising at least one of the foregoing
moieties;

electrostatically shielding the scrivener electrode with the

first shielding electrode and the second shielding elec-
trode;

communicating, in the nanopore, the macromolecule from

the first shielding electrode to the scrivener electrode;

sequentially receiving, in the nanopore at the scrivener

electrode, individual moieties of the macromolecule so

that the third potential of the scrivener electrode

responds to individual moieties in the macromolecule

by:

electrically floating, in an absence of a charged moiety
or a dipolar moiety of the macromolecule, the scriv-
ener electrode at the third potential such that the third
potential is intermediate between the first potential
and the second potential;

changing, in a presence of the charged moiety 224 of
the macromolecule 210, the third potential V3 from
the intermediate potential to electrically read the
presence of the charged moiety 224; and

changing, in a presence of the dipolar moiety 225 of the

macromolecule 210, the third potential from the
intermediate potential to electrically read the pres-
ence of the dipolar moiety 225;
communicating, in the nanopore, the macromolecule from
the scrivener electrode to the second shielding elec-
trode; and
communicating the macromolecule from the nanopore at
the second shielding electrode to expel the macromol-
ecule from the nanopore.
15. A process for reading data from or writing data to a
macromolecule with the molecular scrivener of claim 6, the
process comprising:

10

0

&

0

22

receiving the macromolecule in the nanopore at the third
shielding electrode, the macromolecule comprising a
plurality of moieties, wherein the moieties comprise a
neutral moiety, a charged moiety, a dipolar moiety, or
acombination comprising at least one of the foregoing
moieties;
electrostatically shielding the first writing electrode and
second writing electrode with the third shielding elec-
trode and the first shielding electrode;
communicating, in the nanopore, the macromolecule from
the third shielding electrode to between the first writing
electrode and the second writing electrode;
sequentially receiving, in the nanopore between the first
writing electrode and the second writing electrode,
individual moieties of the macromolecule;
communicating the macromolecule from the first writing
electrode and the second writing electrode to the scriv-
ener electrode through the nanopore in the first shield-
ing electrode;
shielding the scrivener electrode by the first shielding
electrode and the second shielding electrode;
receiving, in the nanopore at the scrivener electrode,
individual moieties of the macromolecule, so that the
third potential of the scrivener electrode responds to
individual moieties in the macromolecule by:
electrically floating, in an absence of the charged
moiety 224 or the dipolar moiety 225 of the macro-
molecule 210, the scrivener electrode at the third
potential such that the third potential V3 is interme-
diate between the first potential V1 and the second
potential V:

changing, in a presence of the charged moiety 224 of
the macromolecule 210, the third potential V3 from
the intermediate potential to electrically read the
presence of the charged moiety 224; and

changing, in a presence of the dipolar moiety 225 of the
macromolecule 210, the third potential from the
intermediate potential to electrically read the pres-
ence of the dipolar moiety 225;
communicating the macromolecule from the nanopore at
the scrivener electrode to the nanopore at the second
shielding electrode; and
communicating the macromolecule from the nanopore at
the second shielding electrode to expel the macromol-
ecule from the nanopore.
16. The process of claim 15, wherein the scrivener ek
trode 212, the first writing electrode, and the second writing
electrode independently comprise an atomically-thin elec-
trically conductive membrane comprising graphene or a
metal,
a thickness of the first shielding electrode, the second
shielding electrode 218, the scrivener electrode, the
first dielectric layer, and the second dielectric layer
independently is from 3.4 A to 3 nm.
17. The process of claim 1, further comprising. when
sequentially receiving, in the nanopore between the first
writing electrode and the second writing electrode, indi-
vidual moieties of the macromolecule:
producing, by the first writing electrode and the second
writing electrode, a writing potential by:
receiving, by the first writing electrode, a fourth poten-
tial; and

receiving, by the second writing electrode, a fifth
potential, wherein the writing potential is a potential
difference between the fourth potential and the fifth
potential;



US 11,507,135 B2

Sheet 30 of 31

210

Nov. 22, 2022

U.S. Patent

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Iength of nanopore 280) from 0.3 nm to 100 nm, specifically
from 1 nm to 20 nm, and more specifically from 1.5 nm to
Snm.

Dielectric layers (226, 230, and the like) electrically
isolate electrodes from another and bound nanopore 280
Exemplary materials for dielectric layers include silicon
oxide, silicon nitride, hafnium oxide, and the like. A thick-
ness of dielectric layers independently can be from 1 nm to
10° nm, specifically from 1.5 nm to 100 nm, and more
specifically from 2 nm to 10 nm. A length and width of
dielectric layers independently can be from 5 nm to 5x10*
nm, specifically from 20 nm to 3x10* nm, and more spe-
cifically from 100 nm to 110° nm. An electrical resistance
of dielectric layers at the voltage difference between scriv-
ener electrode 212 and shielding electrodes 214 and 218
independently can be from 10'7Q to 10°°Q, specifically
from 10'7Q to 10°°Q, and more specifically from 10'7 to
10*Q. In an embodiment, dielectric layers include SiO,,
HfO,, hexagonal boronitride, and the like. Apertures in

dielectric layers communicate macromolecule 210 in nan- 2

opore 280 and independently can have a size (.e., a largest
linear dimension orthogonal to a length of nanopore 280)
from 0.3 nm to 100 nm, specifically from 1 nm to 20 nm, and
more specifically from 1.5 nm to 5 nm.

Detector 240 receives third voltage V3 from scrivener
electrode 212 to detect data stored as bits in macromolecule
210. Exemplary detectors 240 include a high-speed CMOS
transistor, FET, or similar high-gain amplifier. A sensitivity
of detector 240 can be from 0.001 pA/charge to 107
pA/charge, specifically from 0.1 pA/charge to 107
pA/charge, and more specifically from 10 pA/charge to 10°
pA/charge. In an embodiment, detector 240 is field-effect
transistor (FET), specifically a metal-oxide-semiconductor
field-effect transistor (MOSFET), and more specifically an
n-channel MOSFET that includes gate electrode 242, source
electrode 246, drain electrode 244, and body electrode 266
disposed n-well 268, e.g., as shown in FIG. 16. A length and
width of detector 240 can be from 5 nm to 250 nm,
specifically from 10 nm to 130 nm, and more specifically
from 14 nm to 65 nm.

Molecular scrivener 200 can include substrate 264 on
which elements (e.g., shielding electrodes, scrivener elec-
trode, dielectric layers, and detector 240) are disposed as
shown in FIG. 16 to FIG. 28. Substrate 264 can include
silicon on insulator, silicon nitride, silicon oxide to provide
support structures for the device structure and can be a
semiconductor wafer material. Moreover, it will provide
structural stability and a frame for sealing the device in the
fluid-containing operating environment. A thickness of sub-

strate 264 can be from 100 um to 1 mm, specifically from s

100 jum to 500 jum, and more specifically from 200 um to
300 jum. A length and width of substrate 264 can be from 60
hm to 5 mm, specifically from 60 nm to 1 ym, and more
specifically from 60 nm to 100 nm. In an embodiment,

substrate 264 includes an oxide-coated silicon on insulator 5

wafer, An aperture in substrate 264 communicates macro-
molecule 210 out of nanopore 280 and can have a size (
a largest linear dimension orthogonal to a length of nanopore
280) from I nm to 100 nm, specifically from 1 nm to 20 nm,
and more specifically from 1 nm to 10 nm.

Nanopore 280 communicates macromolecule 210 through
molecular scrivener 200 and can be formed in electrodes and
dielectric layers of by, e.g., focused ion beam (e.g., HO
milling, dielectric breakdown, and the like. A size (ie., a
largest linear dimension orthogonal to a length of nanopore
280) can be from 1 nm to 100 nm, specifically from 2 nm to
20 nm, and more specifically from 2 nm to 5 nm.

&

&

at

12

Various power sources (e.g., 236, 238, 262, 282, 284) can
be included in molecular scrivener 200 to provide notice to
elements therein. A voltage from the power sources inde-
pendently can be from -20 V to 20 V, specifically from 1.5
V to 1.5 V, and more specifically from -500 mV to 500 mV.
An electric current from the power sources independently
can be from -500 mA to 500 mA, specifically from -1 pA
to 1 wA, and more specifically from -10 nA to 10 nA. The
power sources can independently provide direct current
voltage or pulsed voltage in a waveform that varies tempo-
rally. Waveform independently can have a duty cycle from
0% to 100%, specifically from 0% to 10%, and more
specifically from 0% to 1%. Moreover, the power source that
is used in bias writing electrodes (212B, 212C) can be
controlled to provide a selected waveform to selectively
write bits to chosen moieties in macromolecule 210.

Molecular scrivener 200 can be made in various ways. In
an embodiment, with reference to FIG. 16 to FIG. 28, a
process for making molecular scrivener 200 includes form-
ing detector 240 on substrate 264 by silicon integrated
circuit production processing as shown in FIG. 16. As shown
in FIG. 17, dielectric layer 270 is formed on substrate 264
and detector 240 by Plasma-enhanced chemical vapor depo-
sition process (PECVD). As shown in FIG. 18, trench 272 is

5 formed in substrate 264 and dielectric layer 270 by Reactive

ion etching (ME). Trench 272 is subsequently filled with
dielectric material by PECVD, and dielectric layer 270 is
planarized by chemical-mechanical polishing (CMP). As
shown in FIG, 19, second shielding electrode 218 is formed
on dielectric layer 270 by chemical vapor deposition (CVD),
and second shielding electrode 218 is patterned by RIE. As
shown in FIG, 20, dielectric layer 230 is formed on second
shielding electrode 218 and dielectric layer 270 by PECVD.
As shown in FIG. 21, scrivener electrode 212 is formed on
dielectric layer 230 by CVD, and scrivener electrode 212 is
patterned by ME. As shown in FIG. 22, dielectric layer 226
is formed on scrivener electrode 212 and dielectric layer 230
by PECVD. As shown in FIG, 23, first shielding electrode
214 is formed on dielectric layer 226 by CVD and then RIE.
As shown in FIG. 24, via 274 is formed through first
shielding electrode 214, dielectric layer 226, dielectric layer
230, second shielding electrode 218, and dielectric layer 270
by RIE. As shown in FIG. 25, dielectric layer is subjected
etching to remove dielectric material from trench 272 to
form cavity 276 under portions of the first shielding elec-
trode 214, scrivener electrode 212, and second shielding,
electrode 218 by timed wet etching. As shown in FIG. 26,
dielectric layer 278 is formed on first shielding electrode 214
and dielectric layer 226 by PECVD. Dielectric layer 278 is
subjected to removal of selected portions to form via 294,
via 296, via 298, via 300, via 302, via 304, via 306, and via
308 by RIE. As shown in FIG. 27, electrical conductor 250
or formed and patterned in via 296, via 298, via 300, via 302,
via 304, via 306, and via 308 by ME.
In an embodiment, molecular scrivener 200 can be made
by fabricating detector 240 by silicon integrated circuit
a silicon integrated circuit processing facility,
and a recess area 272 is formed next to detector 240. This
area is filled back with dielectric layer 270. A thin conduc-
tive layer is then grown, e.g., deposited, and then etched to
form second shield electrode 218. Thin dielectric layer 230
is then deposited. Atomic thin conductive layer is grown
next and patterned into scrivener electrode 212. Another thin
dielectric layer 226 is deposited next. Another thin conduc-
tive layer is then deposited (or grown) and patterned to form
first shield electrode 214. Another dielectric layer is then
deposited. A number of contact holes are then formed to



US 11,507,135 B2

13

enable contact to electrodes and terminals of detector 240.
Metal deposition and patterning creates contact pads for
external contacts to shield electrodes and source, drain,
substrate terminals of detector 240, as well as bridging the
gate terminal of detector 240 to the scrivener electrode.
Access hole 294 is then formed by etching down to the
recess area. A wet etch process selectively etch the dielectric
of layer 270 for a controlled amount by timed etch. Finally,
the nanopore is drilled through from the top to the bottom
recess area.

In an embodiment, molecular scrivener 200 can be made
by fabricating detector 240 by silicon integrated circuit
processing in a silicon integrated circuit processing facility,
and recess area 272 is formed next to detector 240. This area
is filled back with dielectric layer 270. A thin conductive
layer is then grown (or deposited) and then etched to form
the second shield electrode 218. Thin dielectric layer 230 is
then deposited. Atomic thin conductive layer is grown next
and then patterned into the scrivener electrode 212A.

Another thin dielectric layer 226 is deposited next. Another 2

thin conductive layer is then deposited (or grown) and
patterned to form the first shield electrode 214A. Another
thin dielectric layer 226 is then deposited. Next is to deposit
(or grow) another thin conductive layer and pattern it into

writing electrodes 212B and 212C. Another thin dielectric 2:

layer 226 is deposited. Then another thin conductor layer is
deposited (or grown) and patterned into the top shield
electrode 214B.

Tn an embodiment, molecular scrivener 200 can be made
by fabricating detector 240 by silicon integrated circuit
processing in a silicon integrated circuit processing facility,
and recess area 272 is formed next to detector 240. This area
is filled back with dielectric layer 270. A thin conductive
layer is then grown (or deposited) and then etched to form
the second shield electrode 218. Thin dielectric layer 230 is
then deposited. Atomic thin conductive layer is grown next
and then patterned into the scrivener electrode 212A.
Another thin dielectric layer 226 is deposited next. Another
thin conductive layer is then deposited (or grown) and
patterned to form the first shield electrode 214A. Another
thin dielectric layer 226 is then deposited. Next is to deposit
(or grow) another thin conductive layer and pattern it into
writing electrodes 212B and 212C. Another thin dielectric
layer 226 is deposited. Then another thin conductor layer is
deposited (or grown) and patterned into the top shield
electrode 214B. A number of contact holes are then formed
to enable contact to all electrodes and terminals of detector
240. Metal deposition and patterning creates contact pads
for external contacts to shield electrodes, write electrodes

and source, drain, substrate terminals of detector 240, as_5

well as bridging the gate terminal of detector 240 to the
scrivener electrode. A wet etch process selectively etch the
dielectric of layer 270 for a controlled amount by timed etch.
Finally, the nanopore is drilled through from the top to the
bottom recess area.

Molecular scrivener 200 has numerous advantageous and
unexpected benefits and uses. In an embodiment, a process
for reading data from or writing data to macromolecule 210
with molecular scrivener 200 includes: receiving macromol-
ecule 210 in nanopore 280 at first shielding electrode 214,
macromolecule 210 including a plurality of moieties,
wherein the moieties include neutral moiety 223, charged
moiety 224, dipolar moiety 225, or a combination thereof;
electrostatically shielding scrivener electrode 212 with first
shielding electrode 214 and second shielding electrode 218;
communicating, in nanopore 280, macromolecule 210 from
first shielding electrode 214 to scrivener electrode 212;

&

&

s

14

sequentially receiving, in nanopore 280 at scrivener elec-
trode 212, individual moieties of macromolecule 210 so that
third potential V3 of scrivener electrode 212 responds to
individual moieties in macromolecule 210. Scrivener elec-
trode 212 responds to individual moieties in macromolecule
210 by: electrically floating, in an absence of charged moiety
224 or dipolar moiety 225 of macromolecule 210, at third
potential V3 such that third potential V3 is intermediate
between first potential V1 and second potential V2; chang-
ing, in a presence of charged moiety 224 of macromolecule
210, third potential V3 from the intermediate potential to
electrically read the presence of charged moiety 224; and
changing, in a presence of dipolar moiety 225 of macro-
molecule 210, third potential V3 from the intermediate
potential to electrically read the presence of dipolar moiety
225. The process also includes communicating, in nanopore
280, macromolecule 210 from scrivener electrode 212 to
second shielding electrode 218; and communicating macro-
molecule 210 from nanopore 280 at second shielding elec-
trode 218 to expel macromolecule 210 from nanopore 280.

The process can include making a composition that
includes macromolecule 210 disposed in an electrolytic fluid
or dielectric fluid; introducing the composition in compart-
ment 290 of container 288 in which molecular scrivener 200
separates compartment 290 from compartment 292 via nan-
opore 280. First shielding electrode 214 and second shield-
ing electrode 218 can be grounded to shield scrivener
electrode 212 from external electric fields, e.g., from the
electrolytic fluid, compartment 290, compartment 292, and
the like. Macromolecule 210 is communicated through
nanopore 280 with an external electric field produced by
migration electrodes 286 that are disposed in compartment
290 and compartment 292 of container 288. Detector 240 is
controlled to operate in a sub-threshold region or the peak
transconductance region, and drain current is read at a high
bandwidth, e.g., 0.1 GHz or greater. When individual moi-
eties of macromolecule 210, electric charge or dipole, e.g.,
from charged moiety 224 or dipolar moiety 225 change third
potential V3 of scrivener electrode 212. A change in third
potential V3 of scrivener electrode 212 changes electrical
current flowing detector 240, e.g., at source electrode 246 or
drain electrode 244, to determine the presence or identity of
a molecular species of the individual moiety (e.g., 223, 224,
225) of macromolecule 210 in nanopore 280 at scrivener
electrode 212. It is contemplated that time-resolved fluctua-
tion in electrical current at detector 240 provides a unique
fingerprint for electrostatic fields around the moiety at
scrivener electrode 212. When macromolecule 210 is a
nucleic acid containing a plurality of nuclear bases, fluctua-
tion of electrical current from detector 240 is proportional to
a dipole moment of the nucleobase. For nucleobase’s gua-
nine (G), cytosine (C), a thymine (T), adenine (A), and uracil
(U), a magnitude of electrical current (1) produced by
detector 240 is in an order as follows: I(G)~I(C), >I(T)>1
(A). It should be appreciated that this order is due to the
itive magnitude of the permanent electric dipole moment
in the nucleobases and a change in third voltage V3 pro-
duced by the nucleobases arranged in macromolecule 210 as
dipolar moieties 225. It is contemplated that macromolecule
210 can be a linear polymer with segments that produce a
unique current signature, DNA or a polymer with discrete
charges or dipole moments along a backbone of the polymer,
molecular scrivener 200 decodes digital information by
decoding the electrical current with chemical identity of the
segment passing through nanopore 280 in the aperture of
scrivener electrode 212.



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subjecting a first moiety of the macromolecule to the
writing potential;
changing a charge of the first moiety of the macromol-
ecule in response to the writing potential;

communicating the first moiety from the first writing
electrode and the second writing electrode to the scriv-
ener electrode; and

changing the third potential of the scrivener electrode to

detect the first moiety by the scrivener electrode if the
first moiety, after changing the charge of the first
moiety by the writing potential, is charged or dipolar.

18. The process of claim 15, wherein the scrivener elec-
trode 212, the first writing electrode, and the second writing
electrode independently comprise an atomically-thin elec-
trically conductive membrane or a metal.

19. The process of claim 18, wherein the atomically thin
electrically conductive membrane comprises graphene.

20. The process of claim 10, wherein a thickness of the
first shielding electrode, the second shielding electrode 218,
the third shielding electrode, the first writing electrode, the
second writing electrode, the scrivener electrode, the first
dielectric layer, the second dielectric layer, and the third
dielectric layer independently is from 0.34 nm to 3 nm.

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US 11,507,135 B2

Sheet 13 of 31

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U.S. Patent Nov. 22, 2022

Sheet 15 of 31

US 11,507,135 B2

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ore 280 and second shielding electrode 218 and receives
macromolecule 210 from nanopore 280. First control elec-
trode 286 is disposed in first compartment 290 and imparts
a transmissive force on macromolecule 210 disposed in first
compartment 288 to communicate macromolecule 210 from
first compartment 290 to nanopore 280. Second control
electrode 286 is disposed in second compartment 292 and
imparts the transmissive force in nanopore 280 to commu-
nicate macromolecule 210 from nanopore 280 to second
compartment 292. Control electrodes 286 are in electrical
communication with power source 284 that provides a bias
potential to control electrodes 286 by which the transmissive
force is produced and subjected to macromolecule 210.
Power source 282 can include, e.g., power sources (236,
238) to provide input voltage VIN (e.g.. first potential V1,
second voltage V2) to various electrodes, and detector 240
receives scrivener voltage VS (eg., third voltage V3) and
produces the electrical signal. e.g., an electric current, based
‘on scrivener voltage VS. It should be appreciated that FIG.
13 is generic to the molecular scriveners disclosed herein in
that scrivener structure 200A can be any of the molecular
scriveners described above or shown in FIG. 1 to FIG. 12,
wherein FIG. 14 shows that scrivener structure 200A of FIG.
13 is embodied as molecular scrivener 200 shown in FIG. 3.

Molecular scrivener 200 electrostatically reads data (also 2

referred to as a bit) stored in macromolecule 210 or elec-
trochemically writes data to macromolecule 210. Macro-
molecule 210 can include neutral moiety 223, charged
moiety 224, dipolar moiety 225, or a combination thereof.
Exemplary macromolecules 210 include a protein, nucleic
acid, polymer, and the like. Exemplary proteins include
serum albumin, S100B (calcium binding protein), NSE
(neuronal glycolytic enzyme), TNF-«t (tissue necrosis fac-
tor), troponin, creatinine kinase, or myoglobin. Exemplary
nucleic acids include single and double-stranded DNA and
RNA oligonucleotides, messenger RNA, micro RNA, or
siRNA. Exemplary polymers include poly(ethylene glycol),
poly (vinyl pyrrolidone), or poly(styrene sulfonate). Neutral
moieties 223 can include an atom, a nucleobase, or a
monomer. Charged moieties 224 can be negatively charged
or positively charged. Charged moieties 224 can be a
charged form of neutral moiety 223 such as a cation of
neutral moiety 223 or an anion of neutral moiety 223.
Exemplary charged moieties 224 include phosphate, or
sulfonate. Dipolar moiety 225 includes an electric dipole
moment produced by the electronic structure of atoms in
dipolar moiety 225. Exemplary dipolar moieties 225 include
hydrogen cyanide, or cyanamide. A molecular weight of
macromolecule 210 can be from 107 g/mole to 10° g/mole.

In an embodiment, macromolecule 210 is a polymer com- s

prised of nucleic acids, protein amino acid side chains,
synthetic monomers, or a combination of these.

In molecular scrivener 200, scrivener electrode 212 elec-
trostatically reads data stored as bits in macromolecule 210.

Scrivener electrode 212 can include an atomically-thin elec-

trically conductive membrane or a metal as a floating gate
for detector 240. Exemplary atomically-thin electrically
conductive membranes for scrivener electrode 212 include
graphene, carbon nanorod, and other 2-dimensional electri-
cal conductors. Exemplary metals include platinum, gold,
and the like. A thickness of scrivener electrode 212 can be
from 0.1 nm to 10 nm, specifically from 0.1 nm to 5 nm, and
more specifically from 0.15 nm to 2 nm. A length and width
of scrivener electrode 212 independently can be from 0.5 nm
to 1000 nm, specifically from 5 nm to 200 nm, and more
specifically from 10 nm to 50 nm. An electrical resistance of
scrivener electrode 212 can be from 0.12 to 10MQ, spe-

20

&

&

10

cifically from 19 to 1MQ, and more specifically from 10
to 100 kQ. In an embodiment, scrivener electrode 212
includes graphene, platinum, or transition metal dichalcha-
genides. Aperture 222 in scrivener electrode 212 communi-
cates macromolecule 210 in nanopore 280 and can have a
size (ie.,a largest linear dimension orthogonal to a length of
nanopore 280) from 0.3 nm to 100 nm, specifically from 1
nm to 20 nm, and more specifically from 1.5 nm to 5 nm.

Writing electrodes (e.g., 212B, 212C) electrochemically
write data as bits in macromolecule 210 through electron,
transfer of electrons from writing electrodes (212B, 212C)
to a moiety in macromolecule 210. Writing electrodes can
include an atomically-thin electrically conductive mem-
brane or a metal. Exemplary atomically-thin electrically
conductive membrane for writing electrodes include gra-
phene, carbon nanorod, and other 2-dimensional electrical
conductors. Exemplary metals include platinum, gold, and
the like. A thickness of writing electrodes can be from 0.1
nm to 10 nm, specifically from 0.1 nm to 5 nm, and more
specifically from 0.15 nm to 2 nm. A length and width of
writing electrodes independently can be from 0.5 nm to 1000
‘nm, specifically from 5 nm to 200 nm, and more specifically
from 10 nm to 50 nm. An electrical resistance of writing
electrodes can be from 0.1 to 10MQ, specifically from 1
to 1MQ, and more specifically from 10Q to 100 kQ. An
aperture bounded by writing electrodes that communicates
macromolecule 210 in nanopore 280 can have a size (i.e., a
largest linear dimension orthogonal to a length of nanopore
280) from 0.3 nm to 100 nm, specifically from 1 nm to 20
nm, and more specifically from 1.5 nm to 5 nm.

FIG. 15 shows exemplary formats of scrivener electrodes
and writing electrodes. In an embodiment, scrivener elec-
trode is a single clement with an aperture as shown in the
plan view of panel A with a cross-section as shown in panel
B. Scrivener or writing electrodes can include a plurality of
electrodes as shown in panels C and E. According to an
embodiment, with reference to panel C, electrode 212B and
electrode 212C can be disposed opposing one another and
bound an aperture so that the same potential (e.g. third
potential) or different potentials (e.g., fourth potential V4,
fifth potential V5) can be applied thereto. According to an
embodiment, with reference to panel F, electrodes (212A,
212B, 212C, 212D) can be disposed opposing one another to
bound an aperture so that the same potential (e.g. third
potential) or different potentials (e.g., third potential V3,
fourth potential V4, fifth potential V5) can be applied thereto
to separately read and write data in macromolecule 210.

Shielding electrodes (214, 218) shield scrivener electrode
212 and writing electrodes (212B, 212C) from electric fields
exterior to shielding electrodes, e.g., from electrode 286.
Shielding electrodes (214, 218) can include a metal or
conductive oxide to be a ground-plane or shield scrivener
electrode 212 or writing electrodes. Exemplary metals for
shielding electrodes include gold, copper, platinum, and the
like. Exemplary conductive oxides include indium tin oxide
and the like. A thickness of shielding electrodes (214, 218)
independently can be from 0.1 nm to 10 nm, specifically
from 0.1 nm to 5 nm, and more specifically from 0.15 nm to
2 nm. A length and width of shielding electrodes (214, 218)
independently can be from 1 nm to 10° nm, specifically from
10 nm to 10° nm, and more specifically from 50 nm to 300
nm. An electrical resistance of shielding electrodes (214,
218) independently can be from 0.19 to 100 k®, specifically
from 1Q to 10 k®, and more specifically from 10@ to 1 kQ.
Apertures in shielding electrodes (214, 218) communicate
macromolecule 210 in nanopore 280 and independently can
have a size (i.e., a largest linear dimension orthogonal to a



US 11,507,135 B2

Sheet 24 of 31

Nov. 22, 2022

U.S. Patent

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US 11,507,135 B2
Page 2

(56) References Cited

OTHER PUBLICATIONS,

Nam, S-W,, et al., “Ionic Field Effect Transistors with Sub-10 nm
Multiple Nanopores”, Nano Letters, 2009, p. 2044-2048, vol. 9 No.
5

* cited by examiner


US 11,507,135 B2

1
MOLECULAR SCRIVENER FOR READING
OR WRITING DATA TO A
MACROMOLECULE

STATEMENT REGARDING FEDERALLY,
SPONSORED RESEARCH

This invention was made with United States Government
support from the National Institute of Standards and Tech-
nology (NIST), an agency of the United States Department
of Commerce. The Government has certain rights in the
invention. Licensing inquiries may be directed to the Tech-
nology Partnerships Office, NIST, Gaithersburg, Md.,
20899; voice (301) 301-975-2573; email tpo@nist.gov.

BRIEF DESCRIPTION

Disclosed is a molecular scrivener for reading data from
or writing data to a macromolecule, the molecular scrivener
comprising: a pair of shielding electrodes comprising: a first
shielding electrode comprising a first transmission aperture
bounded by the first shielding electrode and that: receives a
first potential; and receives and communicates the macro-
molecule through the first transmission aperture in presence
of the first potential; and a second shielding electrode
comprising a second transmission aperture bounded by the
second shielding electrode and that: receives a second
potential; and receives and communicates the macromol-
ecule through the second transmission aperture, the second
transmission aperture being in fluid communication with and
aligned with first transmission aperture, and the second
transmission aperture being spaced apart from the first
transmission aperture; a scrivener electrode comprising a
third transmission aperture bounded by the scrivener elec-
trode and that: is interposed between the first shielding
electrode and the second shielding electrode; electrically
floats at a third potential such that, in an absence of a
charged moiety or a dipolar moiety of the macromolecule,
the third potential is intermediate between the first potential
and the second potential; and receives the macromolecule
from the first shielding electrode; communicates the mac-
romolecule through the second transmission aperture to the
second shielding electrode; and the third potential changes
ina presence of the charged moiety of the macromolecule to
electrically read the presence of the charged moiety; the
third potential changes in a presence of the dipolar moiety of
the macromolecule to electrically read the presence of the
dipolar moiety; the third transmission aperture being in fluid
communication with and aligned with first transmission

aperture, and is spaced apart from the first shielding elec- s

trode and the second shielding electrode; a first dielectric
layer interposed between the first shielding electrode and the
scrivener electrode and that electrically isolates the first
shielding electrode and the scrivener electrode, the first

dielectric layer comprising a fourth transmission aperture

bounded by the first dielectric layer and that: receives the
macromolecule from the first shielding electrode; and com-
municates the macromolecule through the fourth transmis-
sion aperture to the scrivener electrode, and the fourth
transmission aperture being in fluid communication with and
aligned with first transmission aperture; a second dielectric
layer interposed between the scrivener electrode and the
second shielding electrode and that electrically isolates the
second shielding electrode and the scrivener electrode, the
second dielectric layer comprising a fifth transmission aper-
ture bounded by the second dielectric layer and that:
receives the macromolecule from the scrivener electrode;

20 ii

&

&

2

and communicates the macromolecule through the fifth
‘transmission aperture to the second shielding electrode, and
the fifth transmission aperture being in fluid communication,
with and aligned with first transmission aperture; and a
nanopore that comprises the transmission apertures

A process for reading data from or writing data to a
macromolecule with a molecular scrivener, the process
comprising: receiving the macromolecule in the nanopore at
the first shielding electrode, the macromolecule comprising
a plurality of moieties, wherein the moieties comprise a
neutral moiety, a charged moiety, a dipolar moiety, or a
combination comprising at least one of the foregoing moi-
eties; electrostatically shielding the scrivener electrode with
the first shielding electrode and the second shielding elec-
trode; communicating, in the nanopore, the macromolecule
from the first shielding electrode to the scrivener electrode;
sequentially receiving, in the nanopore at the scrivener
electrode, individual moieties of the macromolecule so that
the third potential of the scrivener electrode responds to
in the macromolecule by: electrically
floating, in an absence of a charged moiety or a dipolar
moiety of the macromolecule, the scrivener electrode at the
third potential such that the third potential is intermediate
between the first potential and the second potential; chang-
ing, in a presence of the charged moiety of the macromol-
ecule, the third potential from the intermediate potential to
electrically read the presence of the charged moiety; and
changing, in a presence of the dipolar moiety of the mac-
romolecule, the third potential from the intermediate poten-
tial to electrically read the presence of the dipolar moiety;
communicating, in the nanopore, the macromolecule from
the scrivener electrode to the second shielding electrode; and
communicating the macromolecule from the nanopore at the
second shielding electrode to expel the macromolecule from
the nanopore.

‘A process for reading data from or writing data to a
macromolecule with a molecular scrivener, the process
comprising: receiving the macromolecule in the nanopore at
the third shielding electrode, the macromolecule comprising
a plurality of moieties, wherein the moieties comprise a
neutral moiety, a charged moiety, a dipolar moiety, or a
combination comprising at least one of the foregoing moi-
eties: electrostatically shielding the first writing electrode
and second writing electrode with the third shielding elec-
trode and the first shielding electrode; communicating, in the
nanopore, the macromolecule from the third shielding elec-
trode to between the first writing electrode and the second
writing electrode; sequentially receiving, in the nanopore
between the first writing electrode and the second writing
electrode, individual moieties of the macromolecule; com-
municating the macromolecule from the first writing elec-
trode and the second writing electrode to the scrivener
electrode through the nanopore in the first shielding elec-
trode; shielding the scrivener electrode by the first shielding
electrode and the second shielding electrode; receiving, in
the nanopore at the scrivener electrode, individual moieties
of the macromolecule, so that the third potential of the
scrivener electrode responds to individual moieties in the
macromolecule by: electrically floating, in an absence of the
charged moiety or the dipolar moiety of the macromolecule,
the scrivener electrode at the third potential such that the
third potential V3 is intermediate between the first potential
and the second potential; changing, in a presence of the
charged moiety of the macromolecule, the third potential
from the intermediate potential to electrically read the
presence of the charged moiety; and changing, in a presence
of the dipolar moiety of the macromolecule, the third



US 11,507,135 B2

19

the fourth transmission aperture 228 being in fluid
communication with and aligned with first transmis-
sion aperture 216;

second dielectric layer 230 interposed between the

scrivener electrode 212 and the second shielding elec-

trode 218 and that electrically isolates the second

shielding electrode 218 and the scrivener electrode 212,

the second dielectric layer 230 comprising a fifth

transmission aperture 232 bounded by the second

dielectric layer 230 and that:

receives the macromolecule 210 from the scrivener
electrode 212: and

communicates the macromolecule 210 through the fifth
transmission aperture 232 to the second shielding
electrode 218, and

the fifth transmission aperture 232 being in fluid com-
munication with and aligned with first transmission
aperture 216; and

a nanopore that comprises the transmission apertures.

2. The molecular scrivener 200 of claim 1, further com-

=

prising a first power source 236 in electrical communication

with the first shielding electrode 214 and that provides a

st

potential to the first shielding electrode 214 such that first
shielding electrode 214 electrostatically shields the scriv-
ener electrode 212 from electrostatic interaction with an
electric field exterior to the nanopore 280.

3. The molecular scrivener 200 of claim 2, further com-

prising a second power source 238 in electrical communi-
cation with the first power source 236 and the second
shielding electrode 218 and that:

PI

provides a second potential to the second shielding elec-
trode 218 such that the second shielding electrode 218
electrostatically shields the scrivener electrode 212
from electrostatic interaction with electric fields exte-
rior to the nanopore 280,

wherein the first power source 236 receives the second
potential from the second power source 238 and pro-
vides the first potential referenced to the second poten-
tial.

4. The molecular scrivener 200 of claim 3, further com-

sing a detector 240 in electrical communication with the

scrivener electrode 212 and that:

detector 240 comprises a field effect transistor that com- 5

receives the third potential from the scrivener electrode
212; and

produces an electrical signal wherein a logarithm of an
electrical current in the electrical signal is proportional
to the third potential from the scrivener electrode 212.

5. The molecular scrivener 200 of claim 4, wherein the

prises:

prisi

a gate electrode 242 in electrical communication with the
scrivener electrode 212 and that receives the third
potential from the scrivener electrode 212; and

»

communicate the electrical current such that an amount
of the electrical current is proportional to the third
potential received at the gate electrode 242 from the
scrivener electrode 212.

6. The molecular scrivener 200 of claim 1, further com-

a first writing electrode 212B disposed on the first shield-
ing electrode 214 and that receives a fourth potential;

a second writing electrode 212C disposed on the first
shielding electrode 214 and that receives a fifth poten-
tial, such that the first writing electrode and the second
writing electrode:

drain electrode 244 and a source electrode 246 that s

3

40

prising:

prising

20

bound the nanopore 280 and are opposingly disposed
on opposite sides of the nanopore 280;
change a charge of a moiety in the nanopore 280
between the first writing electrode and the second
writing electrode when the fourth potential is differ-
ent from the fifth potential;
a third shielding electrode 214B disposed on the first
writing electrode and the second writing electrode and
comprising an electrode aperture, the electrode aperture
bounding the nanopore to receive the macromolecule
and to communicate the macromolecule to the first
shielding electrode after passing between the first writ-
ing electrode and the second writing electrode, such
that the first writing electrode and the second writing
electrode are interposed between the third shielding
electrode 214B and the first shielding electrode; and
a third dielectric layer 226 comprising a dielectric aper-
ture that bounds the nanopore, the third dielectric layer
being interposed between:
the first shielding electrode 214 and the third shielding
electrode,
the first shielding electrode 214 and each of the first
writing electrode and the second writing electrode,
and
the third shielding electrode 214B and each of the first
writing electrode and the second writing electrode,
such that the third dielectric layer 226 electrically
insulates from one another the first shielding elec-
trode, the third shielding electrode, the first writing
electrode, and the second writing electrode.
7. The molecular scrivener 200 of claim 6, further com-

a write power source in electrical communication with the
first writing electrode and the second writing electrode
and that:

provides the fourth potential to the first writing electrode;
and

provides the fifth potential to the second writing elec
trode.

8. The molecular scrivener 200 of claim 7, further com-

prising a field effect transistor that comprises:

a gate electrode 242 in electrical communication with the
scrivener electrode 212 and that receives the third
potential from the scrivener electrode 212: and

a drain electrode 244 and a source electrode 246 that
communicate the electrical current such that an amount
of the electrical current is proportional to the third
potential received at the gate electrode 242 from the
scrivener electrode 212.

9. The molecular scrivener 200 of claim 8, further com-

a container that comprises:
a first compartment that bounds a supply volume that

in fluid communication with the nanopore and the
third shielding electrode; and
provides the macromolecule disposed in the first
compartment to the nanopore; and
a second compartment that bounds a receiver volume
and that is:
in fluid communication with the nanopore and the
second shielding electrode; and
receives the macromolecule from the nanopore;
a first control electrode disposed in the first compart-
ment and that imparts a transmissive force on the
macromolecule disposed in the first compartment to


US 11,507,135 B2

Sheet 27 of 31

Nov. 22, 2022

U.S. Patent

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U.S. Patent

Nov. 22, 2022

Sheet 11 of 31

US 11,507,135 B2

() 200 >B
214B
218 | Tt 2rzc
<4
a ~y
x A ! A
L, LB
(B) 200
280
H
H
214B 4 y bh 2148
226 ' q+ 226
H
2128 —E i ~ 2120
226 —P ' q~ 226
2144-5 Y ~~ 214A
226 —fP ' q~ 226
212A i b 212A
Z 230 —P H br 230
218 i AY 218
x
v
© 200
280
2148 4 Y ~ 2148
226 4 ' t~ 226
H
H
214A + a~ 2144
226 4 i t+ 226
i
H
212A i 212A
Z 230 —P i T~ 230
218-4 i 218
x v

FIG. 11


U.S. Patent

Nov. 22, 21

022 Sheet 14 of 31

US 11,507,135 B2

200
vez 8
(
|—_ 288
210 290
\ _
280
w-4qe--------\- --ee rt ------
1
214
1
26
vin | 2264
i
1
1
il
ann qwaiz 21d
1 H
236 H
23014 23045
i H
1 H 1
H { 1
foo 0) ess sai
y J. 292
) my
( [— 288
238
( (
esa VOI 286

FIG, 14