DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Remarks
This office action fully acknowledges Applicant’s remarks and amendments filed on 06 May 2025.
Claims 1, 3, 6-16, 19, 22, 37, 39, and 44-47 are pending.
Claims 2, 4-5, 17-18, 20-21, 23-36, 38, and 40-43 are cancelled.
No claims are withdrawn.
Claims 45-47 are newly added.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier.
Such claim limitation(s) is/are:
“a…valve mechanism configured to prevent fluid flow through a portion of the fluidic channel arrangement when the speed of rotation of the device is less than a first predetermined value” as in Claims 1, 4-11, 15-16, 39, and 44.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
“a pneumatic gate or ‘air spring’” as in para. [0006] of Applicant’s pre-grant publication US 2023/0061115 A1, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Rejections - 35 USC § 102
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim 44 is rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Kellogg et al. (US PAT 6,063,589 A), referred to hereinafter as “Kellogg”.
Regarding Claim 44, Kellogg teaches a method of moving a fluid sample from a fluid reservoir 507 through a fluidic system formed in a fluidic device 11, the fluidic system comprising a fluid analysis chamber 514, and a fluidic channel arrangement configured to enable fluid communication between the fluid reservoir 507 and the fluid analysis chamber 514 (Fig. 11), the method comprising:
rotating, by a motor, the fluidic device about a central rotational axis at a first rotational speed and for a first duration to generate a first centrifugal force sufficient to drive flow of the fluid sample from the fluid reservoir into a first portion of the fluidic channel arrangement (col. 12, line 18: “After sample loading by a user and filling of metering capillary 202 and overflow capillary 203 at zero rotational speed (which can be performed on the disc separately or with the disc engaged with a spindle of a centrifugal device), the platform is spun at a first rotational speed …” – col. 16, line 11: “Fluid flows through the entry capillary 302 and into the first fluid chamber 303 at a first rotational speed…”);
the fluidic channel arrangement comprising:
a separation chamber 403 configured to remove unwanted particles from the fluid sample prior to the fluid sample entering the fluid analysis chamber (“The use of this platform is illustrated in FIGS. 9A through 9H for separating plasma from whole blood. An imprecise volume (ranging from 1-150 μL of fluid) of blood is applied to the entry port 401 (FIG. 9A). Blood enters the entry capillary 402 by capillary action, and stops at the capillary junction between entry capillary 402 and the separation chamber 403 (FIGS. 9B and 9C).”);
a first fluidic channel 512 extending radially outwardly from the fluid reservoir 507 to the separation chamber 509 and communicating with the separation chamber 509 through a wall in a radially outer region of the separation chamber (the lower wall) (Fig. 11 and “Sacrificial valve 518 or capillary junction 511 are further fluidly connected with channel 512 which is from about 0.1 mm to about 1 mm deep and has a cross-sectional diameter of about 0.1 mm to about 1 mm. Channel 512 extends about 0.1 cm to about 20 cm and is fluidly connected with separation chamber 509 at a point most distal from the axis of rotation.”); and
a second fluidic channel 515 configured for fluid communication between the separation chamber and the fluid analysis chamber 514, the second fluidic channel 515 comprising a pair of channel arms configured to enable fluid flow in substantially antiparallel directions (Fig. 11 shows the channel 515 branching into two separate arms from separation chamber 509 and allowing flow in substantially anti-parallel directions.); and
preventing, by a valve mechanism located in a flow path between the channel arms of the second fluidic channel, onward flow of the fluid sample from the first portion of the fluidic channel arrangement into a second portion of the fluidic channel arrangement via pressure exerted by the valve mechanism in opposition to the first centrifugal force (col. 11, line 26: “The fluid chamber 204 [the valve mechanism] acts as a capillary barrier that prevents fluid flow from metering capillary 202 at a first, non-zero rotational speed f1 sufficient to permit fluid flow comprising overflow from the entry port 201 through overflow capillary 203 and into overflow chamber 205.” – Further, Fig. 11 shows a capillary junction positioned at the branching part of the channel 515, wherein a capillary junction is a type of valve mechanism that exerts pressure in opposition to a flow as claimed.); and
rotating, by the motor, the fluidic device about the central rotational axis at a second higher rotational speed and for a second duration to generate a second centrifugal force sufficient to overcome the pressure of the valve mechanism and drive flow of the fluid sample into the second portion of the fluidic channel arrangement and thereby into the fluid analysis chamber (col. 11, line 31: “The capillary boundary of fluid chamber 204 is constructed to be overcome at a second rotational speed f2 (where f2 >f1).”), as in Claim 44.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3, 6-14, 16, 37, and 39 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (EP 3,988,211 A1), referred to hereinafter as “Lee”, in view of Taylor et al. (US 2016/0167050 A1), referred to hereinafter as “Taylor”, and Kellogg. Kellogg has been discussed above.
Regarding Claim 1, Lee teaches a fluidic device 10 configured to drive movement of fluid under centrifugal force, the fluidic device comprising:
a central region about a central rotational axis of the device and a peripheral region extending radially outwards from the central region (Fig. 3 shows the device 10 having a central region encircled by dashed lines, and a peripheral region covered by and outside said dashed lines.);
a fluid reservoir 110 provided in the central region of the device for receiving a fluid sample (Fig. 7 and [0066]: “…the sample supply chamber 110 is formed at a position close to the center of rotation C…”),
the fluid reservoir 110 in communication with at least one fluidic system (Fig. 7 shows the reservoir 110 in communication with the fluidic systems of the device via distribution channel 115. – [0068]: “The "1-1"-th chamber 120-1 to the "1-n"-th chamber 120-n, which are the first chambers 120, are connected to the sample supply chamber 110 through the distribution channel 115…”),
the at least one fluidic system extending radially outwards from the fluid reservoir 110 into the peripheral region of the device (Fig. 7 shows the fluidic systems comprising chambers 120/130 and channels 125 as extending radially outwards towards the edge of the disc. – [0030]: “The plurality of first chambers, the plurality of second chambers and the reaction chamber may be arranged further from a center of rotation than the sample supply chamber.”);
the at least one fluidic system comprising:
a fluid analysis chamber 150 configured to retain a portion of a fluid sample for analysis ([0123]: “…the reaction chamber 150 includes a detection region 20 to detect the presence of an analyte…”);
a fluidic channel arrangement 115/125 configured to enable fluid communication between the fluid reservoir 110 and the fluid analysis chamber 150 (Fig. 7 shows the reservoir 110 as in communication with the reaction/analysis chamber 150 via distribution channel 115 and siphon channels 125.),
wherein movement of the fluid sample through the fluidic channel arrangement is driven by centrifugal force arising from rotational motion of the device about the central rotational axis ([0072]: “When the platform 100 rotates, the fluid sample accommodated in the sample supply chamber 110 flows through the distribution channel 115.”);
and a first valve mechanism configured to prevent fluid flow through a portion of the fluidic channel arrangement when the speed of rotational motion of the device about the central rotational axis is less than a first predetermined value and to allow fluid flow through the portion of the fluidic channel arrangement when the speed of rotational motion of the device about the central rotational axis is greater than the first predetermined value ([0005]: “…a separate driving source may be required to open and/or close the valve in this case.” – [0152]: “As illustrated in FIG. 13, the rotational speed is increased to v1 to distribute the blood accommodated in the sample supply chamber 110 to the "1-1"-th chamber 120-1, the "1-2"-th chamber 120-2 and the "1-3"-th chamber 120-3 using centrifugal force.” -- Examiner further notes that the recitations “prevent fluid flow…when the speed…is less than a predetermined value” and “allow fluid flow…when the speed…is greater than the first predetermined value” are drawn to conditional process recitations that are both not necessitated by the claim and, as the claims are drawn to a device, such process recitation is not afforded patentable weight.),
wherein the first valve mechanism is arranged between the fluid reservoir and the fluid analysis chamber ([0005]: “…a separate valve may be mounted to a channel.” – Given that all of the channels115/125 of the device are between the fluid reservoir and the reaction/analysis chamber, the valve mounted therein must also be between the fluid reservoir and the reaction/analysis chamber),
as in Claim 1.
Further regarding Claim 1, Lee does not specifically teach the device discussed above wherein the valve mechanism is “a pneumatic gate or ‘air spring’” as in the 35 USC 112f claim interpretation discussed above.
However, Taylor teaches a respective microfluidic device wherein a valve mechanism comprises a gas spring 300 having a chamber which houses an abutment 302 which actuates against a roof 306 of the chamber, wherein the valve chamber holds a predetermined volume of gas defined by the volume of the chamber, and wherein the valve is pneumatically actuated by controlling the pressure of gas contained within the chamber ([0152]); this arrangement ensuring that pressure within the analysis chambers of the device remain equal and that an equal quantity of liquid sample is delivered to a target chamber with each run only after a fluidic operation is performed on the sample liquid, thereby increasing the accuracy and replicability of the assays preformed thereon by preventing premature movement of the liquid sample before necessary fluidic operations are completed (Fig. 11 and [0291]).
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the valve mechanism of Lee to define a chamber for receiving a predetermined quantity of gas, such as suggested by Taylor, so as to ensure that pressure within the analysis chambers of the device remain equal and that an equal quantity of liquid sample is delivered to the analysis chamber with each run, thereby increasing the accuracy and replicability of the assays preformed thereon, and would have a reasonable expectation of success in Lee wherein the pressure pneumatic control of the chamber is achieved via centrifugation.
Further regarding Claim 1, Lee does not specifically teach the device discussed above wherein the fluidic channel arrangement comprises:
a separation chamber configured to remove unwanted particles from the fluid sample prior to the fluid sample entering the fluid analysis chamber; a first fluidic channel extending radially outwardly from the fluid reservoir to the separation chamber and communicating with the separation chamber through a wall in a radially outer region of the separation chamber; and a second fluidic channel configured for fluid communication between the separation chamber and the fluid analysis chamber, the second fluidic channel comprising a pair of channel arms configured to enable fluid flow in substantially antiparallel directions, and wherein the first valve mechanism is located in a flow path between the pair of channel arms of the second fluidic channel, as in Claim 1.
However, Kellogg teaches a respective microfluidic device comprising:
a separation chamber 403 configured to remove unwanted particles from the fluid sample prior to the fluid sample entering the fluid analysis chamber (“The use of this platform is illustrated in FIGS. 9A through 9H for separating plasma from whole blood. An imprecise volume (ranging from 1-150 μL of fluid) of blood is applied to the entry port 401 (FIG. 9A). Blood enters the entry capillary 402 by capillary action, and stops at the capillary junction between entry capillary 402 and the separation chamber 403 (FIGS. 9B and 9C).”);
a first fluidic channel 512 extending radially outwardly from the fluid reservoir 507 to the separation chamber 509 and communicating with the separation chamber 509 through a wall in a radially outer region of the separation chamber (the lower wall) (Fig. 11 and “Sacrificial valve 518 or capillary junction 511 are further fluidly connected with channel 512 which is from about 0.1 mm to about 1 mm deep and has a cross-sectional diameter of about 0.1 mm to about 1 mm. Channel 512 extends about 0.1 cm to about 20 cm and is fluidly connected with separation chamber 509 at a point most distal from the axis of rotation.”); and
a second fluidic channel 515 configured for fluid communication between the separation chamber and the fluid analysis chamber 514, the second fluidic channel 515 comprising a pair of channel arms configured to enable fluid flow in substantially antiparallel directions (Fig. 11 shows the channel 515 branching into two separate arms from separation chamber 509 and allowing flow in substantially anti-parallel directions.);
and wherein the first valve mechanism is located in a flow path between the pair of channel arms of the second fluidic channel (Fig. 11 shows a capillary junction positioned at the branching part of the channel 515, wherein a capillary junction is a type of valve mechanism that exerts pressure in opposition to a flow as claimed.).
Therein, this arrangement provides a structure capable of separating a sample into its components via centrifugal sedimentation, thereby reducing error related to impure samples or matrix effects.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the device of Lee so as to include a separation chamber configured to remove unwanted particles from the fluid sample prior to the fluid sample entering the fluid analysis chamber; a first fluidic channel extending radially outwardly from the fluid reservoir to the separation chamber and communicating with the separation chamber through a wall in a radially outer region of the separation chamber; and a second fluidic channel configured for fluid communication between the separation chamber and the fluid analysis chamber, the second fluidic channel comprising a pair of channel arms configured to enable fluid flow in substantially antiparallel directions, and wherein the first valve mechanism is located in a flow path between the pair of channel arms of the second fluidic channel, such as suggested by Kellogg, so as to provide a structure capable of separating a sample into its components via centrifugal sedimentation, thereby reducing error related to impure samples or matrix effects; and would have a reasonable expectation of success therein.
Regarding Claim 3, the prior art meets the limitations of Claim 1 as discussed above. Further, Lee/Taylor teaches the centrifugal fluidic device discussed above wherein the separation chamber 120 has a depth (d) defining the height between a base of the separation chamber 120 and the top of the separation chamber 120 (Fig. 7 shows that the separation chamber 120 has a depth d along a radius of the disk.), as in Claim 3.
Further regarding Claim 3, Lee/Taylor does not specifically teach the first fluidic channel as arranged to communicate with the separation chamber at or proximate the base of the separation chamber, as in Claim 3.
However, Kellogg teaches a respective centrifugal microfluidic system wherein a sample/ballast chamber 507 communicates with a separation chamber 509 at the "bottom" or most axis-distal extent of the separation chamber (FIG. 12I and col. 44, line 50), wherein this arrangement represents an obvious alternative to that of Lee given that both arrangements commonly serve to provide a liquid sample to a separation chamber.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the centrifugal fluidic device of Lee/Taylor to arrange the first channel which fluidically connects the sample chamber to the separation chamber as connecting at a more axial-distant portion of the separation chamber, such as suggested by Kellogg which provides an obvious alternative arrangement that remains to provide a sample liquid introduced through a channel to a separation chamber, these arrangements are obvious alternatives where all of which commonly represent a channel connected to a chamber to feed a sample liquid into said chamber and would have a reasonable expectation of success therein.
Regarding Claim 6, the prior art meets the limitations of Claim 1 as discussed above. Further, Lee/Taylor teaches the centrifugal fluidic device discussed above wherein the second fluidic channel 125 comprises a first channel arm for fluid communication between the separation chamber 120 and the first valve mechanism (Fig. 7 shows the siphon channel 125 as having a first arm for fluid communication from the separation chamber, wherein this arm provides fluid communication to a valve mechanism positioned in the siphon channel 125 provided by the obvious combination of Lee, Taylor, and Kellogg as discussed above regarding Claims 4 and 5.),
the first channel arm extending radially inwardly from the separation chamber 120 to the first valve mechanism and communicating with the separation chamber 120 through a wall in a radially inner region of the separation chamber 120 (Fig. 7 shows that the first arm of the siphon channel 125 extends radially inwardly, and connects to the separation chamber 120 in a radially inward position.), as in Claim 6.
Regarding Claim 7, the prior art meets the limitations of Claim 1 as discussed above. Further, Lee/Taylor teaches the centrifugal fluidic device discussed above wherein the second fluidic channel comprises a second channel arm for fluid communication between the first valve mechanism and the analysis chamber (Fig. 7 shows that the siphon channel 125 comprises a second arm connecting to the chamber 130.),
the second channel arm extending radially outwardly from the first valve mechanism to the analysis chamber (Fig 7 shows that the second arm of siphon channel extends radially outwardly. As the valve mechanism provided by the obvious combination of Lee, Taylor, and Kellogg, as discussed above regarding Claim 4, is located within the channel 125, at least a portion of the second arm must extend radially outwardly from said valve mechanism.), as in Claim 7.
Regarding Claim 8, the prior art meets the limitations of Claim 1 as discussed above. Further, Lee/Taylor teaches the centrifugal fluidic device discussed above wherein:
the internal corners of the channel arms are rounded, in use to reduce wicking of fluid along the channels in a direction counter to centrifugal forces acting on the fluid (Fig. 7 shows that the corner connecting the two channel arms of the siphon channel 125 is rounded. While Lee does not specifically discuss this arrangement as for countering centrifugal forces acting on the fluid, this recitation is drawn to a process recitation and, as the claims are drawn to a device, such process recitation is not afforded patentable weight. As discussed above, the cited prior art of Lee provides to commensurately disclose the positively claimed structural arrangement/functionality of the channel arms as claimed and is thus fully capable of being utilized for countering centrifugal forces acting on the fluid in as much as presently recited and required herein.), as in Claim 8.
Lee does not specifically teach the second channel wherein the first valve mechanism is located in the flow path between the two channel arms, as in Claim 5.
However, the obvious combination of Lee, Taylor, and Kellogg, as discussed above regarding Claim 4, provides for a valve mechanism located within the second channel. While Lee/Taylor/Kellogg does not specifically teach said valve mechanism as located in a flow path between two channel arms, mere change in orientation or position of elements absent any criticality or unexpected result is an obvious matter of design choice – see MPEP 2144.04(VI)(C). Herein, one of ordinary skill in the art would find it obvious that the device having the claimed relative arrangement of valve and channel arms would not perform differently than the prior art device, absent evidence of criticality, non-obviousness, or unexpected results associated with the position of the valve mechanism.
Regarding Claim 9, the prior art meets the limitations of Claim 4 as discussed above. Further, Lee/Taylor does not specifically teach the centrifugal fluidic device discussed above wherein the first valve mechanism is located radially inwardly of the separation chamber and/or the fluid analysis chamber, as in Claim 9.
However, the obvious combination of Lee, Taylor, and Kellogg, as discussed above regarding Claim 4, provides for a valve mechanism located within the second channel. While Lee/Kellogg does not specifically teach said valve mechanism as located radially inwardly of the separation chamber and/or the fluid analysis chamber, mere change in orientation or position of elements absent any criticality or unexpected result is an obvious matter of design choice – see MPEP 2144.04(VI)(C). Herein, one of ordinary skill in the art would find it obvious that the device having the claimed relative arrangement of valve and chambers would not perform differently than the prior art device, absent evidence of criticality, non-obviousness, or unexpected results associated with the position of the valve mechanism.
Regarding Claim 10, the prior art meets the limitations of Claim 1 as discussed above. Further, Lee does not specifically teach the centrifugal fluidic device discussed above wherein the first valve mechanism defines a chamber for receiving a predetermined quantity of gas, the chamber having maximum dimensions in x, y and z axes, wherein the x axis defines a radial direction, the y axis defines a direction perpendicular to the x axis in a radial plane, and the z axis defines a direction perpendicular to both the x and y axes parallel to the axis of rotation, and wherein the first valve mechanism has a largest dimension in the z axis, as in Claim 10.
However, Taylor teaches a respective microfluidic device wherein a valve mechanism comprises a gas spring 300 having a chamber which houses an abutment 302 which actuates against a roof 306 of the chamber, wherein the valve chamber holds a predetermined volume of gas defined by the volume of the chamber, and wherein the valve is pneumatically actuated by controlling the pressure of gas contained within the chamber ([0152]); this arrangement ensuring that pressure within the analysis chambers of the device remain equal and that an equal quantity of liquid sample is delivered to a target chamber with each run only after a fluidic operation is performed on the sample liquid, thereby increasing the accuracy and replicability of the assays preformed thereon by preventing premature movement of the liquid sample before necessary fluidic operations are completed (Fig. 11 and [0291]).
Further regarding Claim 10, while Lee does not specifically teach the centrifugal fluidic device discussed above wherein the chamber having maximum dimensions in x, y and z axes, wherein the x axis defines a radial direction, the y axis defines a direction perpendicular to the x axis in a radial plane, and the z axis defines a direction perpendicular to both the x and y axes parallel to the axis of rotation, and wherein the first valve mechanism has a largest dimension in the z axis, mere change in shape absent evidence to criticality, non-obviousness, or unexpected results associated with the claimed shape is an obvious matter of design choice – see MPEP 2144.04(IV)(B).
Herein, one of ordinary skill in the art would find it obvious to position the valve spring with a greatest dimension in the z axis, as contextually defined above, so as to provide the gas contained therein with the greatest surface area force in the x axis so as to provide enough force to actuate a membrane.
Regarding Claim 11, the prior art meets the limitations of Claim 1 as discussed above. Further, Lee/Taylor does not specifically teach the centrifugal fluidic device discussed above wherein the first valve mechanism is arranged circumferentially around and adjacent the fluid reservoir, as in Claim 11.
However, the obvious combination of Lee, Taylor, and Kellogg, as discussed above regarding Claim 4, provides for a valve mechanism located within the second channel. While Lee/Kellogg does not specifically teach said valve mechanism as arranged circumferentially around and adjacent the fluid reservoir, mere change in orientation or position of elements absent any criticality or unexpected result is an obvious matter of design choice – see MPEP 2144.04(VI)(C). Herein, one of ordinary skill in the art would find it obvious that the device having the claimed relative arrangement of valve and fluid reservoir would not perform differently than the prior art device, absent evidence of criticality, non-obviousness, or unexpected results associated with the position of the valve mechanism.
Regarding Claim 12, the prior art meets the limitations of Claim 1 as discussed above. Further, Lee/Taylor teaches the centrifugal fluidic device discussed above wherein the fluid analysis chamber is arranged radially outwards of the separation chamber (Fig. 7 shows that the analysis chamber 150 is located radially outwards respective to the separation chamber 120, the analysis chamber 150 being closer to the edge of the disc.), as in Claim 12.
Regarding Claim 13, the prior art meets the limitations of Claim 1 as discussed above. Further, Lee does not specifically teach the centrifugal fluidic device discussed above wherein the fluid analysis chamber is cylindrical having a substantially circular cross section in an axial plane of the device, as in Claim 13.
However, mere change in shape absent evidence to criticality, non-obviousness, or unexpected results associated with the claimed shape is an obvious matter of design choice – see MPEP 2144.04(IV)(B). Herein, one of ordinary skill in the art would find it obvious that the claimed cylindrical analysis chamber would not function differently than the trapezoidal analysis chamber 150 of lee, given that both chambers commonly serve as regions for holding a sample through which light is transmitted and detected (Lee [0145]).
Regarding Claim 14, the prior art meets the limitations of Claim 1 as discussed above. Further, Lee teaches the centrifugal fluidic device discussed above wherein the at least one fluidics system contains in a region thereof at least one drug in a form suitable for dissolution in the fluid sample ([0113]: “The second chambers 130 may accommodate only a sample (e.g., blood), or may have a reagent or reactant [i.e. the at least one drug or equivalents thereof] pre-stored therein. The reagent or reactant may be used, for example, to perform pretreatment or first order reaction for blood, or to perform a simple test prior to the main test. In the illustrated exemplary embodiment, binding between an analyte and a first marker conjugate occurs in the second chambers 130.”), as in Claim 14.
Regarding Claim 16, the prior art meets the limitations of Claim 15 as discussed above. Further, Lee teaches the centrifugal fluidic device discussed above wherein at least one fluidics system contains at least one drug to be assayed against the fluid sample, wherein the drug is provided in in a first drug retention chamber located between the first valve mechanism and the fluid analysis chamber ([0113]: “The second chambers 130 may accommodate only a sample (e.g., blood), or may have a reagent or reactant [i.e. the at least one drug or equivalents thereof] pre-stored therein. The reagent or reactant may be used, for example, to perform pretreatment or first order reaction for blood, or to perform a simple test prior to the main test. In the illustrated exemplary embodiment, binding between an analyte and a first marker conjugate occurs in the second chambers 130.”), as in Claim 16.
Regarding Claim 37, the prior art meets the limitations of Claim 1 as discussed above. Further, Lee/Taylor does not specifically teach the centrifugal fluidic device discussed above comprising at least one fluidic system containing an antibiotic or an antibiotic combination
However, Kellogg teaches a respective centrifugal microfluidic device wherein an antibiotic array (the antibiotic sensitivity panel) comprising a plurality of antibiotics is provided to assay the antibiotic sensitivity of a biological liquid sample (col. 10, line 37).
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the device of Lee/Taylor to include an antibiotic array, such as suggested by Kellogg, so as to provide a suitable structure for performing antibiotic sensitivity assays when bacterial analysis of a sample is desired, as is similarly contemplated by Lee which teaches biological fluid analysis, and would have a reasonable expectation of success therein.
Regarding Claim 39, Lee teaches an apparatus comprising: a fluidic device comprising:
a central region about a central rotational axis of the device and a peripheral region extending radially outwards from the central region (Fig. 3 shows the device 10 having a central region encircled by dashed lines, and a peripheral region covered by and outside said dashed lines.);
a fluid reservoir 110 provided in the central region of the device for receiving a fluid sample (Fig. 7 and [0066]: “…the sample supply chamber 110 is formed at a position close to the center of rotation C…”),
the fluid reservoir 110 in communication with at least one fluidic system (Fig. 7 shows the reservoir 110 in communication with the fluidic systems of the device via distribution channel 115. – [0068]: “The "1-1"-th chamber 120-1 to the "1-n"-th chamber 120-n, which are the first chambers 120, are connected to the sample supply chamber 110 through the distribution channel 115…”),
the at least one fluidic system extending radially outwards from the fluid reservoir 110 into the peripheral region of the device (Fig. 7 shows the fluidic systems comprising chambers 120/130 and channels 125 as extending radially outwards towards the edge of the disc. – [0030]: “The plurality of first chambers, the plurality of second chambers and the reaction chamber may be arranged further from a center of rotation than the sample supply chamber.”);
the at least one fluidic system comprising:
a fluid analysis chamber 150 configured to retain a portion of a fluid sample for analysis ([0123]: “…the reaction chamber 150 includes a detection region 20 to detect the presence of an analyte…”);
a fluidic channel arrangement 115/125 configured to enable fluid communication between the fluid reservoir 110 and the fluid analysis chamber 150 (Fig. 7 shows the reservoir 110 as in communication with the reaction/analysis chamber 150 via distribution channel 115 and siphon channels 125.),
wherein movement of the fluid sample through the fluidic channel arrangement is driven by centrifugal force arising from rotational motion of the device about the central rotational axis ([0072]: “When the platform 100 rotates, the fluid sample accommodated in the sample supply chamber 110 flows through the distribution channel 115.”);
a first valve mechanism configured to prevent fluid flow through a portion of the fluidic channel arrangement when the speed of rotational motion of the device about the central rotational axis is less than a first predetermined value and to allow fluid flow through the portion of the fluidic channel arrangement when the speed of rotational motion of the device about the central rotational axis is greater than the first predetermined value ([0005]: “…a separate driving source may be required to open and/or close the valve in this case.” – [0152]: “As illustrated in FIG. 13, the rotational speed is increased to v1 to distribute the blood accommodated in the sample supply chamber 110 to the "1-1"-th chamber 120-1, the "1-2"-th chamber 120-2 and the "1-3"-th chamber 120-3 using centrifugal force.” -- Examiner further notes that the recitations “prevent fluid flow…when the speed…is less than a predetermined value” and “allow fluid flow…when the speed…is greater than the first predetermined value are drawn to conditional process recitations that are both not necessitated by the claim and, as the claims are drawn to a device, such process recitation is not afforded patentable weight.),
wherein the first valve mechanism is arranged between the fluid reservoir and the fluid analysis chamber ([0005]: “…a separate valve may be mounted to a channel.” – Given that all of the channels115/125 of the device are between the fluid reservoir and the reaction/analysis chamber, the valve mounted therein must also be between the fluid reservoir and the reaction/analysis chamber),
a motor 310 for driving rotational motion of the fluidic device about the rotational axis of the fluidic device ([0057]: “The microfluidic device 10 may be mounted to a test device 300 including a drive unit 310 and a controller 320, and may be rotated by the drive unit 310 as shown in FIG. 1.”;
and a controller 320 executing non-transitory machine readable code to cause the motor to control flow of the fluid sample from the fluid reservoir to the fluid analysis chamber of the at least one fluidic system ([0042-0043]: “…a controller configured to control the rotary drive unit and the magnetic module. When a fluid is to be transferred from the metering chamber to the reaction chamber, the controller is configured to rotate the platform and at a predefined time during rotation of the platform, move the magnetic module to a position over or under the platform such that the magnetic module faces the magnetic body.”), as in Claim 39.
Further regarding Claim 39, Lee does not specifically teach the device discussed above wherein the valve mechanism is “a pneumatic gate or ‘air spring’” as in the 35 USC 112f claim interpretation discussed above.
However, Taylor teaches a respective microfluidic device wherein a valve mechanism comprises a gas spring 300 having a chamber which houses an abutment 302 which actuates against a roof 306 of the chamber, wherein the valve chamber holds a predetermined volume of gas defined by the volume of the chamber, and wherein the valve is pneumatically actuated by controlling the pressure of gas contained within the chamber ([0152]); this arrangement ensuring that pressure within the analysis chambers of the device remain equal and that an equal quantity of liquid sample is delivered to a target chamber with each run only after a fluidic operation is performed on the sample liquid, thereby increasing the accuracy and replicability of the assays preformed thereon by preventing premature movement of the liquid sample before necessary fluidic operations are completed (Fig. 11 and [0291]).
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the valve mechanism of Lee to define a chamber for receiving a predetermined quantity of gas, such as suggested by Taylor, so as to ensure that pressure within the analysis chambers of the device remain equal and that an equal quantity of liquid sample is delivered to the analysis chamber with each run, thereby increasing the accuracy and replicability of the assays preformed thereon, and would have a reasonable expectation of success in Lee wherein the pressure pneumatic control of the chamber is achieved via centrifugation.
Further regarding Claim 39, Lee does not specifically teach the device discussed above wherein the fluidic channel arrangement comprises:
a separation chamber configured to remove unwanted particles from the fluid sample prior to the fluid sample entering the fluid analysis chamber; a first fluidic channel extending radially outwardly from the fluid reservoir to the separation chamber and communicating with the separation chamber through a wall in a radially outer region of the separation chamber; and a second fluidic channel configured for fluid communication between the separation chamber and the fluid analysis chamber, the second fluidic channel comprising a pair of channel arms configured to enable fluid flow in substantially antiparallel directions, and wherein the first valve mechanism is located in a flow path between the pair of channel arms of the second fluidic channel, as in Claim 39.
However, Kellogg teaches a respective microfluidic device comprising:
a separation chamber 403 configured to remove unwanted particles from the fluid sample prior to the fluid sample entering the fluid analysis chamber (“The use of this platform is illustrated in FIGS. 9A through 9H for separating plasma from whole blood. An imprecise volume (ranging from 1-150 μL of fluid) of blood is applied to the entry port 401 (FIG. 9A). Blood enters the entry capillary 402 by capillary action, and stops at the capillary junction between entry capillary 402 and the separation chamber 403 (FIGS. 9B and 9C).”);
a first fluidic channel 512 extending radially outwardly from the fluid reservoir 507 to the separation chamber 509 and communicating with the separation chamber 509 through a wall in a radially outer region of the separation chamber (the lower wall) (Fig. 11 and “Sacrificial valve 518 or capillary junction 511 are further fluidly connected with channel 512 which is from about 0.1 mm to about 1 mm deep and has a cross-sectional diameter of about 0.1 mm to about 1 mm. Channel 512 extends about 0.1 cm to about 20 cm and is fluidly connected with separation chamber 509 at a point most distal from the axis of rotation.”); and
a second fluidic channel 515 configured for fluid communication between the separation chamber and the fluid analysis chamber 514, the second fluidic channel 515 comprising a pair of channel arms configured to enable fluid flow in substantially antiparallel directions (Fig. 11 shows the channel 515 branching into two separate arms from separation chamber 509 and allowing flow in substantially anti-parallel directions.);
and wherein the first valve mechanism is located in a flow path between the pair of channel arms of the second fluidic channel (Fig. 11 shows a capillary junction positioned at the branching part of the channel 515, wherein a capillary junction is a type of valve mechanism that exerts pressure in opposition to a flow as claimed.).
Therein, this arrangement provides a structure capable of separating a sample into its components via centrifugal sedimentation, thereby reducing error related to impure samples or matrix effects.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the device of Lee so as to include a separation chamber configured to remove unwanted particles from the fluid sample prior to the fluid sample entering the fluid analysis chamber; a first fluidic channel extending radially outwardly from the fluid reservoir to the separation chamber and communicating with the separation chamber through a wall in a radially outer region of the separation chamber; and a second fluidic channel configured for fluid communication between the separation chamber and the fluid analysis chamber, the second fluidic channel comprising a pair of channel arms configured to enable fluid flow in substantially antiparallel directions, and wherein the first valve mechanism is located in a flow path between the pair of channel arms of the second fluidic channel, such as suggested by Kellogg, so as to provide a structure capable of separating a sample into its components via centrifugal sedimentation, thereby reducing error related to impure samples or matrix effects; and would have a reasonable expectation of success therein.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Lee in view of Taylor and Kellogg, as applied to Claims 1, 3, 6-14, 16, 37, and 39 above, and in further view of Lee et al. (US 2010/0175994 A1), referred to hereinafter as “Lee-2”.
Regarding Claim 15, the prior art meets the limitations of Claim 1 as discussed above. Further, Lee/Taylor/Kellogg teaches the centrifugal fluidic device discussed above wherein the fluidic channel arrangement further comprises a third fluidic channel, the third fluidic channel arranged to extend from the fluid analysis chamber (Lee Fig. 7 shows a third channel extending from an overflow portion 140 of the analysis chamber 150 to a waste chamber 170.), as in Claim 15.
Further regarding Claim 15, Lee/Taylor/Kellogg does not specifically teach the third channel as extending to a second valve mechanism, and wherein the second valve mechanism is located radially inwardly of the fluid analysis chamber, as in Claim 15.
However, Lee-2 teaches a centrifugal microfluidic device comprising an analysis chamber and a waste chamber, wherein a channel fluidically connects said analysis chamber and waste chamber, and wherein a valve mechanism is arranged in said channel to prevent premature discharge of the liquid sample contained within the analysis chamber to the waste chamber ([0011-0012]).
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the device of Lee/Taylor/Kellogg to include a second air spring valve mechanism in the third channel fluidically connecting the fluid analysis chamber with the waste chamber, such as suggested by Lee-2, so as to prevent premature discharge of the liquid sample contained within the analysis chamber to the waste chamber, thereby reducing measurement error due to sample leaving the analysis chamber unwantedly.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Lee in view of Taylor and Kellogg, as applied to Claims 1, 3, 6-14, 16, 37, and 39 above, and in further view of Hoffmann et al. (US 2015/0273470 A1), referred to hereinafter as “Hoffmann”.
Regarding Claim 19, the prior art meets the limitations of Claim 1 as discussed above. Further, Lee/Taylor/Kellogg does not specifically teach the centrifugal fluidic device discussed above further comprising a bacterial growth media configured to promote growth of bacteria potentially present in the fluid sample when mixed with the fluid sample; the growth media provided in the fluid reservoir or in a growth media compartment that is in fluid communication with the fluid reservoir, as in Claim 19.
However, Hoffmann teaches a respective microfluidic device wherein reaction chambers 140 (the growth media compartments) are filled with a bacterial growth medium to amplify a bacterial concentration within a liquid biological sample before performing an analysis, thereby improving the accuracy and precision of the analysis results (Fig. 1 and [0037]).
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the device of Lee/Taylor/Kellogg to include a growth media compartment, such as suggested by Hoffmann, so as to amplify a bacterial concentration within a liquid sample when bacterial analysis is desired, thereby improving the accuracy and precision of the analysis results, and would have a reasonable expectation of success therein.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Lee in view of Taylor and Kellogg, as applied to Claims 1, 3, 6-14, 16, 37, and 39 above, and in further view of Alonzo et al. (US 2019/0217293 A1), referred to hereinafter as “Alonzo”.
Regarding Claim 22, the prior art meets the limitations of Claim 1 as discussed above. Further, Lee/Taylor/Kellogg teaches the centrifugal fluidic device discussed above wherein the central region of the fluidic device comprises a sample receiving well 111 for receiving a fluid sample (Fig. 7 and [0104]: “A sample introduction inlet 111 is provided at one side of the sample supply chamber 110, through which an instrument such as a pipette may be used to introduce blood into the sample supply chamber 110.”), as in Claim 22.
Further regarding Claim 22, Lee/Taylor/Kellogg does not specifically teach the device discussed above wherein the sample receiving well is communicable with the fluid reservoir via a growth media compartment containing a growth media and a filter element arranged, in use, to filter the mixture of fluid sample and growth media before it enters the fluid reservoir, as in Claim 22.
However, Alonzo teaches a respective microfluidic device wherein a sample receiving well 202 is communicable with an analysis chamber 220 via a filter chamber 204 (the growth media compartment) containing growth media and a filter element 206 therein for filtering the mixture of fluid sample and growth media before it enters the fluid analysis chamber 220, wherein this arrangement provides for bacterial amplification prior to analysis performed in the analysis chamber, thereby improving the accuracy and precision of the analysis results (Fig. 2 and [0085]).
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the device of Lee/Taylor/Kellogg to include a growth media compartment containing a growth media and a filter element arranged therein between the sample inlet and the analysis chamber, such as suggested by Alonzo, so as to provide for bacterial amplification prior to analysis performed in the analysis chamber, thereby improving the accuracy and precision of the analysis results, and would have a reasonable expectation of success therein.
Claims 45-47 are rejected under 35 U.S.C. 103 as being unpatentable over Lee in view of Taylor and Kellogg, as applied to Claims 1, 3, 6-14, 16, 37, and 39 above, and in further view of Geisberg (US 2018/0156796 A1), referred to hereinafter as “Geisberg”.
Regarding New Claims 45-47, Lee/Taylor/Kellogg does not specifically teach the device discussed above comprising the antibiotics listed in Claims 45-46, nor specifically teaches the device comprising a bactericidal agent as in Claim 47.
However, Geisberg teaches an analysis performed by a microfluidic device ([0070]) where